Previous changes

June 2026 — minor update. QOF indicator table updated for 2026/7.

May 2026 — minor update. Minor update in format in the Antidiabetic drugs section. 

March 2026 — minor update. Updated to align with the 2026 update to NICE guidance Type 2 Diabetes in adults: management.

January 2026 — minor update. Risk of non-arteritic anterior ischaemic optic neuropathy added as an adverse effect of semaglutide in line with updated manufacturer's SPC.

July 2025 — reviewed. A literature search was conducted in April 2025 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. No major changes to the recommendations have been made.

March 2025 — minor update. Information on which measure of kidney function to use when considering dosage adjustments in people with renal impairment taking alogliptin or vildagliptin was changed from eGFR to CrCl. 

December 2024 — minor update.  Updated QOF indicator set to align with NHS England 2024 indicators. 

November 2024 — minor update.  Added information regarding the need for further evaluation of black people with known or potential sickle cell trait and the interpretation of HbA1c results, which may underestimate past glycaemia. 

October 2024 — minor update. Information that HbA1c should not be used to diagnose diabetes mellitus in people with HIV has been removed from this topic in line with the BHIVA guidelines for the routine investigation and monitoring of adult HIV 1 positive individuals (2019 interim update). Cutaneous amyloidosis added as an adverse effect of liraglutide.

August 2024 — minor update. Added information on drug interaction between tirzepatide and oral contraceptives in line with advice from the MHRA and an update to the manufacturers summary of product characteristics. Information that HbA1c may be used to diagnose type 2 diabetes in children and young people has been added to this topic in line with the updated International Society for Pediatric and Adolescent Diabetes (ISPAD) guideline. 

May 2024 — minor update. Recommendations on screening for, and management of, diabetic kidney disease have been removed from this topic and links added to the CKS topic on Chronic kidney disease. 

April 2024 — minor update. Intestinal obstruction has been added as an adverse effect of semaglutide in line with the manufacturer's SPC.

March 2024 — minor update. Phimosis has been added as an adverse effect of dapagliflozin in line with the manufacturer's SPC.

November 2023 — minor update. The section on antidiabetic drugs has been clarified and prescribing information on tirzepatide has been added. 

October 2023 — minor update. Information on when to consider dapagliflozin treatment has been clarified.

August 2023 — minor update. Delayed gastric emptying has been added as a possible adverse effect of semaglutide in line with the manufacturer's updated Summary of Product Characteristics. Revised threshold for prescribing dapagliflozin in chronic kidney disease to align with NICE TA775. 

July 2023 — minor update. Revised the dosing of canagliflozin dependent on eGFR in line with the manufacturer's SPC. 

March 2023 — minor update. Updated quality statements in line with the publication of NICE Diabetes type 2 Quality Standard [QS209]. Added recommendation to consider adding finerenone as an option for treating stage 3 and 4 chronic kidney disease (with albuminuria) associated with type 2 diabetes in adults in line with the NICE Technology Appraisal [TA877]. 

February 2023 — minor update. A link has been added from the prescribing section on SGLT-2 inhibitors to the section on Diabetic kidney disease and more information about prescribing dapagliflozin in chronic kidney disease has been added.  

January 2023 — minor update. Added the quality standards from the updated NICE Diabetes in pregnancy Quality standard [QS109]. The section on managing foot problems has been updated in line with the NICE guideline Diabetic foot problems: prevention and management.  

October 2022 — minor update. Added delayed gastric emptying as an adverse effect of lixisenatide as per the manufacturer's updated SPC. Replaced advice for adult kidney disease from the management of children and young people section. 

September 2022 — minor update. Added cholecystitis and cholelithiasis as new potential adverse effects of exenatide from an update to the manufacturers summary of product characteristics.  Also a new interaction noted relating to the use of lithium and dapagliflozin from an update to the manufacturers SPC. 

August 2022 — minor update. Recommendations on blood pressure targets have been updated in line with the updated NICE guideline Hypertension in adults: diagnosis and management [NG136].

June 2022 — minor update. Adverse effect of increased risk of vitamin B12 deficiency associated with metformin added, based on a drug safety update from MHRA.  Revised dosing of metformin modified release in renal impairment to align with standard metformin. 

April 2022 — minor update. Adverse effects and contraindications of metformin and SGLT-2 inhibitors updated in line with revised manufacturer's SPCs.

March 2022 — minor update. Updated renal thresholds for prescribing empagliflozin in line with updated manufacturers summary of product characteristics. 

February 2022 — minor update. Added information relating to the use of SGLT-2 inhibitors as an adjunct to treatment for adults with type 2 diabetes and chronic heart failure, atherosclerotic cardiovascular disease based on the updated NICE guideline Type 2 diabetes in adults: management [NG28]. 

November 2021 — minor update. Added information relating to the use of SGLT2 inhibitor as an adjunct to treatment for adults with type 2 diabetes and chronic kidney disease based on the updated NICE guideline Type 2 diabetes in adults: management [NG28]. 

July 2021 — minor update. Dose adjustments relating to impaired renal function on canagliflozin updated in line with the manufacturer's SPC. 

June 2021 — minor update. Adverse effects of GLP-1 receptor agonists updated in line with revised manufacturer's SPC.

May 2021 — minor update. Adverse effects of SGLT-2 inhibitors updated in line with revised manufacturer's SPC. 

April 2021 — minor update. Adverse effects of DPP-4 inhibitors updated in line with revised manufacturer's SPC. 

November 2020 to January 2021 — reviewed. A literature search was conducted in November 2020 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. The topic has undergone minor restructuring to improve clarity and navigation. The recommendations have been updated in line with current literature. Information on the hyperglycaemic emergency complication of hyperosmolar hyperglycaemic state (HHS) has been added.

April 2020 — minor update. Adverse effects of sodium-glucose cotransporter 2 (SGLT-i2) inhibitors have been updated to include bullous pemphigoid, in line with the manufacturers' Summary of Product Characteristics (SPC) update. 

September 2019 — minor update. The section on antihypertensive treatment has been updated in line with the NICE clinical guideline Hypertension in adults: diagnosis and management [NICE 2019].

July 2019 — minor update. Angioedema has been recognised as a very rare skin and subcutaneous tissue disorder in people taking dapagliflozin for type 2 diabetes.

May 2019 — minor update. Prescribing information updated for liraglutide as the manufacturer advises that blood glucose self-monitoring is recommended to adjust the dose of sulfonylurea and insulin, especially when liraglutide is started and insulin is reduced, using a stepwise approach. Diabetic ketoacidosis has been reported in insulin-dependent patients after rapid discontinuation or dose reduction of insulin [ABPI, 2019].

August 2017 — minor update. Bullous pemphigoid added as an adverse effect of gliptins as per updates to the manufacturer's Summary of Product Characteristics (SPC). 

May 2017 — minor update. Information added on sodium–glucose cotransporter 2 (SGLT-2) inhibitors to reflect changes to the NICE clinical guideline Type 2 diabetes in adults: management.

January 2017 — minor update. Information added on organic cation transporters in the section on prescribing Metformin, as per the manufacturer's Summary of Product Characteristics (SPC) for glucophage. Information also added on potential drug interaction with St John's wort, as per an update to the manufacturer's SPC for diamicron.

December 2016 — minor update.

• Information added on use of pioglitazone in patients with active bladder cancer following FDA review [FDA, 2016].
• The adverse effects section for pioglitazone has been updated with information that bone fractures have been reported in both men and women [ABPI, 2016].
• Information from a systematic review has been added to the basis for recommendation in the section on managing cardiovascular risk [BMJ, 2016].
• The adverse effects and interactions sections have been updated to reflect changes to the manufacturer's Summary of Product Characteristics (SPC) for vildagliptin [ABPI, 2016].

November 2016 — minor update.

• The National Institute for Health and Care Excellence (NICE) quality standards for diabetes in children and young people have been added to this topic [NICE, 2016].
• Additional information regarding referral to the diabetic eye screening programme has been added to reflect the November 2016 update to the NICE clinical guideline. 
• A recommendation from a Medicines and Healthcare products Regulatory Agency (MHRA) Drug safety update SGLT2 inhibitors: updated advice on the risk of diabetic ketoacidosis [MHRA, 2016] has been added to this topic.
• The adverse effects section for sulfonylureas has been updated to include information about skin and subcutaneous tissue disorders and drug rash with eosinophilia and systemic symptoms (DRESS) with gliclazide [ABPI, 2016].

October 2016 — minor update. Increased lipase and increased amylase added as common adverse effects of liraglutide. 

April to July 2016 — reviewed. A literature search was conducted in April 2016 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. The recommendations have been updated in line with recommendations in the National Institute for Health and Care Excellence (NICE) guidelines Type 2 diabetes in adults: management (2015) and Diabetes (type 1 and type 2) in children and young people: diagnosis and management (2015).

October 2015 — minor updates:

• Immune-mediated necrotizing myopathy (IMNM) has been included as a very rare adverse effect of some statins based on updates to manufacturers' Summaries of Product Characteristics (SPCs).
• The prescribing information section has been updated to reflect the US Food and Drug Administration (FDA) adverse event database, which now includes severe joint pain as an adverse effect of DPP-4 inhibitors.

September 2015 — minor updates. The prescribing information section has been updated to include:

• Pruritus, arthropathy, and bullous pemphigoid as adverse effects of sitagliptin, based on an update to the manufacturer's SPC.
• Advice from the Medicines and Healthcare products Regulatory Agency (MHRA) and the drug manufacturers that combination use of drugs from two classes of the renin-angiotensin system (RAS) blocking agents (for example an angiotensin-converting enzyme [ACE] inhibitor plus an angiotensin-II receptor antagonist or aliskiren) is not recommended.
• Other common adverse effects of ACE inhibitors and a drug interaction between ramipril tablets (Tritace®) and vildagliptin, based on updates to the SPC for Tritace®.

August 2015 — minor update. The prescribing information section on clarithromycin has been updated to reflect changes to the manufacturer's SPC.

July 2015 — minor update. Based on an update to the manufacturer's SPC, constipation has been added as an adverse effect of saxagliptin.

April 2015 — minor update. Update to the text to clarify the MHRA warning that aliskiren should not be prescribed with different classes of RAS blocking drugs.

March 2015 — minor update. Update to the text to reflect the adverse effect of rapid weight loss resulting in cholelithiasis for exenatide, based on the manufacturer's SPC.

February 2015 — minor update. Update to reflect the National Institute for Health and Care Excellence (NICE) guideline and address differences between this and the current Clinical Knowledge Summaries (CKS) type 2 diabetes topic.

September 2014 — two minor updates:

• The recommendations in the Scenario on managing lipids have been updated in line with the revised NICE guideline Lipid modification: Cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease (2014).
• The World Health Organization (WHO) recommendation to use HbA1c to confirm the diagnosis of diabetes type 2 has been included.

August 2014 — minor update to reflect additional caution of history of pancreatitis for saxagliptin and vildagliptin, based on the manufacturers' SPCs.

July 2014 — two minor updates: 

• The evidence section on lipid modification therapy has been deleted because it is currently being updated in line with the NICE guideline on lipid modification.
• Advice from the MHRA to not prescribe medicines from different classes of RAS blocking agents in combination (for example an ACE inhibitor plus an AIIRA) has been incorporated into the topic.

March 2014 — minor update. Information on the pharmacological treatment of neuropathic pain has been removed and a link to the CKS topic on Neuropathic pain - drug treatment inserted.

January 2014 — minor update. The prescribing information regarding antiplatelet drugs has been removed and a link to the CKS topic on Antiplatelet treatment inserted.

December 2013 — two minor updates:

• Prescribing information has been updated in line with the SPC for perindopril.
• Text has been removed from the section on antiplatelet treatment and links added to the updated CKS topic on Antiplatelet treatment.

September 2013 — minor update to the text to reflect current European Medicines Agency (EMA) recommendations regarding metoclopramide.

July 2013 — minor update. Links to the Driver and Vehicle Licensing Agency (DVLA) website have been updated.

June 2013 — minor update. The 2013 Quality and Outcomes Framework (QOF) options for local implementation have been added to this topic.

February 2013 — minor update. The 2013 QIPP options for local implementation have been added to this topic.

January 2013 — minor update. Removed the black triangle status from sitagliptin as this is no longer a black triangle drug. Change to the text to reflect safety advice issued by the MHRA regarding gliptins. Update to the text to reflect safety advice issued by the MHRA for simvastatin.

November 2012 — minor update. The links to the electronic medicines website (www.medicines.org.uk) have been updated.

October 2012 — minor update. The 2012 QIPP options for local implementation have been added to this topic.

July 2012 — minor update. The section on goals and outcome measures has been updated to reflect changes to the NICE Diabetes in adults quality standards.

April 2012 — minor update. The 2012/2013 QOF indicators have been added to this topic. 

February 2012 — minor update. Issued in April 2012. This topic has been updated to include: 

• A section on management of a person with type 2 diabetes during periods of fasting (such as during Ramadan).
• Information from guidelines commissioned by NHS Diabetes on 'Recognition, treatment and prevention of hypoglycaemia in the community'.
• New information about doses, contraindications, and adverse effects of gliptins.
• Information from the MHRA about the slight risk of hyperglycaemia and diabetes with statin use.
• Update to the manufacturers' SPCs to clarify that although liraglutide is not licensed for use in combination with insulin, Levemir® (insulin detemir [recombinant human insulin analogue]) is licenced to be used as add-on therapy to liraglutide treatment.

October to December 2011 — updated. Issued in January 2012. This topic has been updated to include: 

• The MHRA warning on the interaction between systemic fusidic acid and statins.
• Information on saxagliptin (Onglyza®) and linagliptin (Trajenta®), two new dipeptidyl peptidase-4 inhibitors licensed for the treatment of adults with type 2 diabetes to improve glycaemic control.
• Information on the NICE technology appraisal Liraglutide for the treatment of type 2 diabetes mellitus.
• Information on fitness to drive from the DVLA's At a glance guide to the current medical standards of fitness to drive.
• A tabulated version of the treatment recommendations for blood glucose control, to aid navigation.

September 2011 — minor update. There is a small increased risk of bladder cancer associated with pioglitazone use. This information is based on advice from the MHRA and the EMA.  Cough is included as a very rare but possible adverse effect of candesartan. This information is based on the updated SPC for Amias®. 

June 2011 — minor update. The 2011/2012 QOF indicators and the 2010/2011 QIPP options for local implementation have been added to this topic. 

March 2011— topic structure revised to ensure consistency across CKS topics. No changes to clinical recommendations have been made. The NICE quality standards on the management of diabetes have been added.

November 2010 — minor update. CKS is aware that some primary care trusts are still recommending gabapentin over pregabalin due to the significant price differences between these two drugs. Based on feedback from CKS external reviewers, gabapentin is also offered by CKS as an alternative to pregabalin if there is a local decision to prefer gabapentin over pregabalin for painful diabetic neuropathy. Issued in November 2010.

October 2010 — minor update. Information on fitness to drive from the DVLA's At a glance guide to the current medical standards of fitness to drive has been added. 

September 2010 — minor update. The topic has been amended to reflect information in the MHRA guidance Rosiglitazone (Avandia, Avandamet): Recommended withdrawal from clinical use updated. Rosiglitazone is no longer available. The UK marketing authorisation has been suspended because the benefits are no longer considered to outweigh the increase in cardiovascular risk associated with its use.  The supporting evidence section on Antiplatelet drugs has been updated. 

August 2010 — minor update. The MHRA has issued a reminder that the current cardiovascular restrictions on rosiglitazone must be followed whilst the EMA review on the safety of rosiglitazone is ongoing. 

July 2010 — updated to include new recommendations on the management of painful diabetic neuropathy published in the NICE guideline Neuropathic pain: the pharmacological management of neuropathic pain in adults in non-specialist settings.

June 2010 — minor update. Advice that vitamin B12 deficiency may sometimes be caused by long-term treatment with metformin has been added to the adverse effects section. 

April 2010 — minor update. The recommendations from the NHS Diabetes Working Group on when to recommend self-monitoring of blood glucose has been included in the relevant sections. It supports the advice that self-monitoring of blood glucose should only be offered with appropriate education and clear objectives in specific circumstances. Advice from the Scottish Intercollegiate Guidelines Network (SIGN) that aspirin should not be offered for primary prevention of cardiovascular disease (CVD) in people with diabetes has also been added.

December 2009 — minor update. The recommendations on when to consider antiplatelet therapy for primary prevention of CVD have been updated. 

July to October 2009 — updated to include evidence and recommendations from the NICE short guideline Type 2 diabetes: newer agents for blood glucose control in type 2 diabetes and new information on reporting HbA1c levels. A reminder from the MHRA that aspirin is not licensed for primary prevention of CVD has also been added.

July 2009 — minor update to clarify the advice from the MHRA on the use of ACE inhibitors and AIIRAs in women who are breastfeeding. 

June 2009 — minor update to include drug safety advice from the MHRA on the use of ACE inhibitors and AIIRAs in women who are breastfeeding. 

May 2009 — updated to include the indicators related to diabetes mellitus in the QOF of the General Medical Services contract in the section on goals and outcome measures. 

April 2009 — minor update. Losartan has been reclassified as a black triangle drug by the MHRA. However, this is due to harmonisation of the SPCs across the European Union, not because of any newly identified safety issues. 

July to December 2008 — converted from CKS guidance to CKS topic structure. The evidence base has been reviewed in detail, and recommendations are more clearly justified and transparently linked to the supporting evidence. This CKS topic replaces previous topics on Diabetes — foot disease, Diabetes — glycaemic control, Diabetes — hypertension, Diabetes — renal disease, and Diabetes — retinopathy. Significant changes include: 

• The recommendation to prescribe aspirin to all people with diabetes over the age of 50 years.
• The recommendation to start insulin (before triple therapy with oral antidiabetic drugs) in primary care, providing the expertise and support are available.
• The rapid-acting insulin secretagogues (nateglinide and repaglinide) are recommended as an alternative to sulphonylureas for people with irregular mealtimes. Prescriptions are included.
• Recommendations for management of hypertension have altered — all people with type 2 diabetes should now be started on an ACE inhibitor first-line (unless contraindicated).
• The decision on when to prescribe a lipid-modifying drug is more clearly expressed.
• Treatment targets for lipids have changed.
• Ezetimibe is now recommended, in addition to simvastatin, as an alternative to a higher-intensity statin for people with CVD or microalbuminuria who have not reached lipid targets on a lower-intensity statin. Prescriptions are included.

New evidence

Evidence-based guidelines

• MHRA (2025) GLP-1 medicines for weight loss and diabetes: what you need to know. Medicines and Healthcare products Regulatory Agency. [Free Full-text]
• NICE (2026) Teplizumab for delaying the onset of stage 3 type 1 diabetes in people 8 years and over with stage 2 type 1 diabetes. National Institute for Health and Care Excellence. https://www.nice.org.uk [Free-Full text]

HTAs (Health Technology Assessments)

• NICE (2025) Tirzepatide for treating type 2 diabetes. National Institute for Health and Care Excellence. https://www.nice.org.uk [Free Full-text]

Economic appraisals

No new economic appraisals relevant to England since 1 April 2025.

Systematic reviews and meta-analyses

No new systematic reviews or meta-analysis which reach the CKS threshold for inclusion since 1 April 2025.

Primary evidence

No new primary evidence which reaches the CKS threshold for inclusion published since 1 April 2025.

New policies

No new policies since 1 April 2025.

New safety alerts

No new safety alerts since 1 April 2025.

Changes in product availability

• New product Tzield (teplizumab) 2 mg/2 mL concentrate for solution for infusion. This anti-CD3 monoclonal antibody that modifies CD8+ T lymphocytes is licensed to delay the onset of Stage 3 type 1 diabetes in adult and paediatric patients ≥8 years with Stage 2 type 1 diabetes. It is administered by IV infusion once daily for 14 days. See more here.

Interpreting HbA1c results

• HbA1c should not be used to diagnose diabetes mellitus in the following groups:
  • Children and young people under 18 years of age. 
  • Pregnant women or women within 2 months postpartum. 
  • People with symptoms of diabetes for less than 2 months. 
  • People at high diabetes risk who are acutely ill.
  • People taking medication that may cause hyperglycaemia (for example, long-term corticosteroid treatment). 
  • People with acute pancreatic damage, including pancreatic surgery.
  • People with end-stage renal disease (ESRD). See the CKS topic on Chronic kidney disease for more information.
• HbA1c should be interpreted with caution in people with abnormal red blood cell turnover or abnormal haemoglobin type: 
  • Abnormal haemoglobin, such as haemoglobinopathy, including sickle cell trait. Black people (including those with potentially undiagnosed sickle cell trait) may need further evaluation when considering an HbA1c test result as the result may underestimate past glycaemia. 
  • Severe anaemia (any cause). See the CKS topics on Anaemia - iron deficiency and Anaemia - B12 and folate deficiency for more information.
  • Altered red cell lifespan (for example, post-splenectomy). 
  • A recent blood transfusion.

[WHO, 2011; Kilpatrick and Atkin, 2014; Milne, 2020; Davies, 2022; NICE, 2022b]

Basis for recommendation

The recommendations on diagnosis are largely based on the National Institute for Health and Care Excellence (NICE) guidelines Type 2 diabetes in adults: management [NICE, 2022b], and Diabetes (type 1 and type 2) in children and young people: diagnosis and management [NICE, 2023c], the World Health Organization (WHO) publications Classification of diabetes mellitus [WHO, 2019] and Use of glycated haemoglobin (HbA1c) in the diagnosis of diabetes mellitus [WHO, 2011], the American Diabetes Association (ADA) and European Association for the Study of Diabetes (EASD) consensus report Management of hyperglycaemia in type 2 diabetes [Davies, 2022], the International Society for Pediatric and Adolescent Diabetes (ISPAD) clinical practice consensus guideline Definition, epidemiology, and classification of diabetes in children and adolescents [Libman, 2022], and expert opinion in review articles on HbA1c in diabetes diagnosis [Kilpatrick and Atkin, 2014] and on diabetic reviews [Milne, 2020].

When to suspect type 2 diabetes

• The information on possible presenting symptoms of type 2 diabetes is largely based on the ADA/EASD consensus report [Davies, 2022].
• The information on the presence of risk factors is based on the WHO publication [WHO, 2019] and the NICE clinical guideline [NICE, 2022b].
• The information on the definition of persistent hyperglycaemia is based on the WHO publication [WHO, 2019].
• The recommendation to repeat the HbA1c or plasma glucose level if the person is asymptomatic is based on the WHO publication, which advises this should be carried out as soon as possible on a subsequent day to confirm the diagnosis of diabetes [WHO, 2019]. The recommendation to monitor the person depending on clinical judgement if repeat testing is normal is pragmatic, based on what CKS considers to be good clinical practice.
• The information that transient hyperglycaemia in the context of acute illness or stress is not diagnostic of diabetes is extrapolated from the paediatric ISPAD clinical practice consensus guidelines [Libman, 2022]. 

Interpreting HbA1c results

• Expert opinion in a review article notes various advantages in the use of HbA1c to diagnose diabetes, including no requirement for the person to fast or perform an oral glucose tolerance test. In addition, it assesses blood glucose control over the preceding 8–12 weeks and there is lower biological variability with HbA1c than with fasting glucose or 2-hour post-glucose load concentration [Kilpatrick and Atkin, 2014].
• The information on clinical circumstances when HbA1c results should not be used or interpreted with caution is based on the NICE clinical guideline [NICE, 2022b], the WHO publication [WHO, 2011], the ADA/EASD consensus report [Davies, 2022], and expert opinion in review articles [Kilpatrick and Atkin, 2014; Milne, 2020].
  • The WHO publication recommends HbA1c as a diagnostic test for diabetes, providing there are no conditions present that preclude its accurate measurement [WHO, 2011]. 
• The recommendation to seek specialist advice if there is uncertainty about the use of HbA1c in diagnosis or monitoring is extrapolated from advice within the NICE clinical guideline which suggests seeking specialist advice if there are unexplained discrepancies between HbA1c and other glucose measurements [NICE, 2022b]. It is also pragmatic, based on what CKS considers to be good clinical practice.

Factors increasing the likelihood of type 2 diabetes

• The information that a diagnosis of type 2 diabetes is more likely in adults if there are no features of type 1 diabetes or other types or secondary causes of diabetes,  is extrapolated from information within the NICE clinical guideline Diabetes (type 1 and type 2) in children and young people: diagnosis and management [NICE, 2023c].

Basis for recommendation

The recommendations on diagnosis in children and young people are largely based on the National Institute for Health and Care Excellence (NICE) guideline Diabetes (type 1 and type 2) in children and young people: diagnosis and management [NICE, 2023c], the International Society for Pediatric and Adolescent Diabetes (ISPAD) clinical practice consensus guidelines Definition, epidemiology, and classification of diabetes in children and adolescents [Libman, 2022], and Type 2 diabetes mellitus in children and adolescents [Shah, 2024], the World Health Organization (WHO) publication Classification of diabetes mellitus 2019 [WHO, 2019], and expert opinion in a review article on youth-onset type 2 diabetes [Candler, 2018].

When to consider type 2 diabetes

The information on the possible presenting symptoms of type 2 diabetes is based on the NICE clinical guideline [NICE, 2023c], and the ISPAD clinical practice guidelines [Libman, 2022; Shah, 2024]. The information on the sign of acanthosis nigricans is based on the NICE clinical guideline [NICE, 2023c].

Arranging immediate same-day referral 

• The recommendation to arrange immediate paediatric diabetes team referral if type 2 diabetes is suspected is based on the ISPAD clinical practice consensus guidelines, which recommend prompt referral to a team with expertise in managing children with diabetes [Libman, 2022].
  • It notes that waiting to confirm hyperglycaemia is unnecessary, and if ketones are present in blood or urine treatment is urgent, because ketoacidosis in children and young people can evolve rapidly.
  • In addition, specialist tests including diabetes-associated autoantibody titres and/or molecular genetic testing to differentiate between type 1, type 2, monogenic, and other types of diabetes may be needed, which have important implications for treatment and future education [Libman, 2022]. This approach is supported by expert opinion in a review article [Candler, 2018].
  • CKS notes that the NICE clinical guideline does not recommend the routine measurement of autoantibodies associated with type 1 diabetes at initial presentation to support a diagnosis of type 2 diabetes if the test is negative, however, these tests may be considered after initial presentation [NICE, 2023c].

Precipitating factors

• Precipitating factors of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycaemic state (HHS) include:
  • Infection.
  • Inadequate insulin or non-adherence with insulin treatment.
  • New onset of diabetes mellitus or other physiological stress (such as trauma or surgery).
  • Other medical conditions (such as hypothyroidism or pancreatitis). 
  • Drugs (such as corticosteroids, diuretics, atypical antipsychotics, and sympathomimetic drugs such as salbutamol).

[MHRA, 2016; Wolfsdorf, 2018; French, 2019; MHRA, 2020; NICE, 2023c]

Basis for recommendation

The recommendations on diagnosis of hyperglycaemic emergencies are largely based on the National Institute for Health and Care Excellence (NICE) clinical guideline Diabetes (type 1 and type 2) in children and young people: diagnosis and management [NICE, 2023c], the International Society for Pediatric and Adolescent Diabetes (ISPAD) clinical practice consensus guidelines Diabetic ketoacidosis and the hyperglycemic hyperosmolar state [Glaser, 2022], the British Society for Paediatric Endocrinology and Diabetes (BSPED) publication Guideline for the management of children and young people under the age of 18 years with diabetic ketoacidosis [BSPED, 2021], the Medicines and Healthcare products Regulatory Agency (MHRA) Drug safety updates SGLT2 inhibitors: updated advice on the risk of diabetic ketoacidosis [MHRA, 2016] and SGLT2 inhibitors: monitor ketones in blood during treatment interruption for surgical procedures or acute serious medical illness [MHRA, 2020], and expert opinion in review articles on diabetic ketoacidosis (DKA) and hyperglycaemic hyperosmolar state (HHS) [French, 2019], on SGLT-2 inhibitors [Morris, 2019], and on sick-day rules [Down, 2020].

When to suspect DKA

• The information that DKA usually presents in people with diabetes with high blood glucose levels above 11 mmol/L is extrapolated from limited evidence and consensus opinion in the BSPED guideline [BSPED, 2021].
• The information on the clinical features suggesting a diagnosis of DKA is based on the NICE clinical guideline [NICE, 2023c], the BSPED guideline [BSPED, 2021], the ISPAD clinical practice consensus guidelines [Glaser, 2022], and expert opinion in review articles [French, 2019; Down, 2020].
• The information on the definitions of high urinary ketone and capillary blood ketone levels is based on the BSPED guideline [BSPED, 2021], the ISPAD clinical practice consensus guidelines [Glaser, 2022], and expert opinion in a review article [Down, 2020].
  • CKS notes that the BSPED guideline recommends using near-patient testing for blood ketone level for the diagnosis of DKA. If this is not available, it suggests using urinary ketone levels to make the diagnosis.
  • The information that urinary ketones must be read 15 seconds after the stick is dipped is based on the BSPED guideline.
• The information that DKA may develop in people with diabetes with normal blood glucose levels is based on the NICE clinical guideline [NICE, 2023c], and is extrapolated from limited evidence and consensus opinion in the BSPED guideline [BSPED, 2021] and expert opinion in review articles, which note various potential causes of so-called 'euglycaemic DKA' [French, 2019; Morris, 2019]. In addition, an MHRA drug safety update recommends stopping SGLT-2 inhibitors and checking blood ketone levels if there is acute serious illness [MHRA, 2020]. 

When to suspect HHS

• The information on the clinical features suggesting a diagnosis of HHS is based on the BSPED guideline [BSPED, 2021], the ISPAD clinical practice consensus guidelines [Glaser, 2022], and expert opinion in review articles [French, 2019; Down, 2020].

Basis for recommendation

The information on hypoglycaemia is extrapolated from the National Institute for Health and Care Excellence (NICE) clinical guideline Type 1 diabetes in adults: diagnosis and management [NICE, 2020], the joint European Society of Cardiology (ESC)/European Association for the Study of Diabetes (EASD) publication ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD [Cosentino, 2020], and expert opinion in a review article on diabetic reviews [Milne, 2020].

• Hypoglycaemia should be prevented in people with diabetes, particularly in advanced disease or cardiovascular disease, as it can cause arrhythmias and myocardial ischaemia. Severe hypoglycaemia is associated with increased risk of death and worsened cardiovascular prognosis, based on limited evidence and consensus opinion [Cosentino, 2020].

What initial information and advice should I offer an adult with type 2 diabetes?

Ensure that the person has an individualized care plan, taking into account their age, preferences, co-morbidities, and risk of adverse effects from polypharmacy and their likelihood of benefiting from long-term interventions.

• Offer referral to a structured group education programme such as the DESMOND (Diabetes Education for Self-Management for Ongoing and Newly Diagnosed) programme, for the person and their family/carers.
  • This should be offered at or around the time of diagnosis, with annual reinforcement and review.
  • Advise that the website www.desmond.nhs.uk may have useful information.
• Ensure that the person and their family/carers know how to contact the specialist diabetes team, if appropriate.
• Provide advice on sources of information and support.
  • Diabetes UK (website available at www.diabetes.org.uk) — a national charity that provides information, support, and advocacy for people with diabetes and their families. It has a confidential helpline (0345 123 2399) and hosts an online community for peer support, as well as a wide range of education and information patient resources.
  • For detailed information on managing other lifestyle and cultural issues, such as driving, fasting, holiday and travel, insurance, and shift work, see the CKS topic on Insulin therapy in type 2 diabetes.
• Provide advice on lifestyle measures, such as diet, exercise, and weight loss, if appropriate.
• Assess for associated anxiety and depression, and manage appropriately. See the CKS topics on Generalized anxiety disorder and Depression for more information.
  • The Diabetes UK patient resource Diabetes and your emotions may be helpful.
• Advise about sexual health, contraception, and the importance of pre-pregnancy counselling, if appropriate. See the CKS topics on Contraception - assessment and Pre-conception - advice and management for more information.
  • The Diabetes UK patient resource Planning for a pregnancy when you have diabetes may be helpful.
• Offer immunization against influenza and pneumococcal infection. See the CKS topics on Immunizations - seasonal influenza and Immunizations - pneumococcal for more information.
• Advise about entitlement to free NHS prescriptions if the person uses insulin or antidiabetic medication. See the Diabetes UK section on Free prescriptions (England) for more information.
• Advise the person to always wear or carry some form of diabetes identification, such as a:
  • MedicAlert® bracelet, necklace, or watch (available from www.medicalert.org.uk).
  • Diabetes identity card or wristband (available from www.diabetes.org.uk).
• Advise that HbA1c should be measured at 3–6 monthly intervals initially until stable on unchanging antidiabetic treatment, and then every 6 months to ensure adequate blood glucose control. See the section on Treatment targets for more information.
• Advise that screening for complications will be arranged at diagnosis and then annually thereafter.

What are the treatment targets for adults with type 2 diabetes?

Offer lifestyle advice and drug treatment(s) to achieve an individualized target HbA1c level, to minimize the risk of long-term complications, depending on the person's age, preferences, risk of adverse effects, and co-morbidities.

• Educate the person about their individual recommended HbA1c target, and encourage measures to achieve and maintain it, where possible. Recommended HbA1c targets are:
  
  • 48 mmol/mol (6.5%)
    • For people managing type 2 diabetes with diet and lifestyle alone
    • For people managing type 2 diabetes with diet and lifestyle, combined with a single drug not associated with hypoglycaemia (such as metformin)
  • 53 mmol/mol (7.0%)
    • For people on drug treatment associated with hypoglycaemia (such as a sulfonylurea): .
  • Consider using the NICE patient decision aid to support these decisions. 
• Measure HbA1c levels at 3–6 monthly intervals until the HbA1c is stable on unchanging treatment, then at 6-monthly intervals.
• If HbA1c levels are not adequately controlled by a single drug and rise to 58 mmol/mol (7.5%) or higher:
  • Reinforce advice on lifestyle including diet.
  • Assess the person's adherence to antidiabetic drug treatment.
  • Support the person to aim for an HbA1c level of 53 mmol/mol (7.0%).
  • Intensify antidiabetic drug treatment, if appropriate. See the section on Antidiabetic drugs for more information.
• HbA1c targets should be individualized according to the person's duration of diabetes, co-morbidities, and age, and may be reduced if:
  • There are adverse effects from treatment (such as hypoglycaemia), or treatment is affecting the person's quality of life.
    • Tight blood glucose control and possible hypoglycaemia may be inappropriate for people at risk of falls, those with impaired awareness of hypoglycaemia, and people who drive or operate machinery.
  • The person is unlikely to achieve longer-term risk-reduction benefits, for example if they have significant co-morbidities or a reduced life expectancy.
• If the person achieves an HbA1c level that is lower than their target and there are no adverse effects such as hypoglycaemia:
  • Encourage them to maintain it.
  • Be aware of alternative reasons for a low HbA1c level, such as deteriorating renal function or sudden weight loss. See the CKS topic on Chronic kidney disease for more information.
  • Consider stopping any medication that is not effective at review.
• Do not routinely recommend self-monitoring of blood glucose levels.
  • Advise the person on the need to self-monitor blood glucose levels if they:
    • Are using insulin therapy. See the CKS topic on Insulin therapy in type 2 diabetes for more information.
    • Have evidence of hypoglycaemic episodes.
    • Are taking a drug that may increase the risk of hypoglycaemia while driving or operating machinery (such as a sulfonylurea). 
    • Are pregnant or planning a pregnancy. See the CKS topic on Pre-conception - advice and management for more information.
    • Note: advise that blood glucose levels may increase with acute intercurrent illness or infection. See the section on Managing intercurrent illness for more information.
  • Provide appropriate advice on driving if the person is self-monitoring blood glucose levels.
    • See the Driver and Vehicle Licensing Agency (DVLA) document Assessing fitness to drive: a guide for medical professionals for more information.
  • Consider the need for short-term self-monitoring of blood glucose levels:
    • When starting treatment with corticosteroids, or
    • To confirm suspected hypoglycaemia.
• If routine self-monitoring of blood glucose levels is indicated, review the person at least annually to check:
  • Self-monitoring skills, the quality and frequency of testing, and the equipment used. See the CKS topic on Insulin therapy in type 2 diabetes for information on blood glucose meters, lancets, and strips.
  • The person knows how to interpret blood glucose results, and what action to take if they are too high or too low.
  • The impact of self-monitoring on the person's quality of life and the continued benefit to the person. 

Which antidiabetic drugs are available for adults with type 2 diabetes?

If an adult with type 2 diabetes is hyperglycaemic with symptoms, consider the need for immediate insulin therapy or treatment with a sulfonylurea, depending on specialist advice, and review treatment when blood glucose control has been achieved. 

For all other adults, offer individualized antidiabetic treatment depending on the person's HbA1c treatment target, age, preferences, comorbidities, contraindications, weight, risks and benefits of treatment, and polypharmacy. Consider the effectiveness of the medications prescribed in terms of metabolic response, cardiovascular and renal protection, safety and tolerability. Consider also the need for monitoring, licensed indications, a combination of medications, and cost, as well as choosing the drugs with the lowest acquisition cost. 

• For people already started on standard-release metformin, continue this if it is effective. Switch to modified-release metformin if standard-release metformin is not tolerated, or if this is the person's preference.
• GLP-1 receptor agonists include liraglutide, dulaglutide, and semaglutide. For subcutaneous semaglutide, this only includes doses up to 1 mg once a week.
• When starting multiple medications, start them sequentially, not simultaneously. Only move on to the next step having reached and confirmed the maximum tolerable dose of the current medication.

For adults with type 2 diabetes and no relevant comorbidity.

• For adults with type 2 diabetes and no relevant comorbidity, offer:
  • Modified-release metformin and an SGLT2-inhibitor.
    • If metformin is contraindicated or not tolerated, offer an SGLT2-inhibitor as monotherapy.
• For adults with type 2 diabetes and no relevant comorbidity who need further medicines to reach their individualised glycaemic targets:
  • Offer to add a DPP-4 inhibitor to their current treatment
  • If this is contraindicated, not tolerated or is not effective, offer to add:
    • A sulfonylurea, or
    • Pioglitazone, or
    • An insulin-based treatment.

For adults with type 2 diabetes and heart failure.

• For adults with type 2 diabetes and heart failure, offer: 
  • Modified-release metformin and an SGLT2-inhibitor.
• If metformin is contraindicated or not tolerated, offer:
  • An SGLT2-inhibitor as monotherapy.
• For adults with type 2 diabetes and heart failure, who need further medicines to reach their individualised glycaemic targets:
  
  • Offer to add a DPP-4 inhibitor to their current treatment
  • If this is contraindicated, not tolerated or not effective, offer to add:
    
    • A sulfonylurea, or
    • An insulin-based treatment.

For adults with type 2 diabetes and atherosclerotic cardiovascular disease.

• For adults with type 2 diabetes and atherosclerotic cardiovascular disease, offer: 
  • Modified-release metformin, and 
  • An SGLT2-inhibitor, and 
  • Subcutaneous semaglutide up to 1mg once per week. 
• If metformin is contraindicated or not tolerated, offer:
  • An SGLT2-inhibitor, and subcutaneous semaglutide up to 1mg once per week.
• For adults with type 2 diabetes and atherosclerotic cardiovascular disease who need further medicines to reach their individualised glycaemic targets, offer to add to their current treatment:
  • A sulfonylurea, or
  • Pioglitazone, or
  • An insulin-based treatment.

For adults with early-onset type 2 diabetes.

• For adults with early-onset type 2 diabetes (diagnosed before the age of 40), offer modified-release metformin and an SGLT2 inhibitor, and consider adding either:
  • A GLP-1 receptor agonist or tirzepatide.
• If metformin is contraindicated or not tolerated, offer an SGLT2-inhibitor and consider adding either:
  • A GLP-1 receptor agonist or tirzepatide.
• For adults with early-onset type 2 diabetes who need further medicines to reach their individualised glycaemic targets, consider adding a GLP-1 receptor agonist or tirzepatide.
• For adults with early onset type 2 diabetes who need further medicines to reach their individualised glycaemic targets and for whom a GLP-1 receptor agonist or tirzepatide is contraindicated, not tolerated or not appropriate:
  • Offer to add a DPP-4 inhibitor to their current treatment
  • If this is contraindicated, not tolerated or is not effective, offer to add:
    • A sulfonylurea, or
    • Pioglitazone, or
    • An insulin-based treatment. 
• For adults with early onset type 2 diabetes who need further medicines to reach their individualised glycaemic targets and are taking a GLP-1 receptor agonist or tirzepatide, offer to add to their current treatment:
  • A sulfonylurea or
  • Pioglitazone or
  • An insulin-based treatment.

For adults with type 2 diabetes who are living with obesity.

• For adults with type 2 diabetes who are living with obesity, offer:
  • Modified-release metformin and an SGLT2-inhibitor.
    • If metformin is contraindicated or not tolerated, offer an SGLT2-inhibitor as monotherapy.
• Consider adding a GLP-1 receptor agonist or tirzepatide for adults with type 2 diabetes who are living with obesity, if:
  • They have been taking initial therapy for at least 3 months, and
  • Further medicines are needed to reach their individualised glycaemic targets, and
  • They are not already taking a GLP-1 receptor agonist or tirzepatide.
• For adults with type 2 diabetes who are living with obesity who need further medicines to reach their individualised glycaemic targets and for whom a GLP-1 receptor agonist or tirzepatide is contraindicated, not tolerated, not appropriate or not effective:
  • Offer to add a DPP-4 inhibitor to their current treatment
  • If this is contraindicated, not tolerated or not effective, offer to add:
    • A sulfonylurea, or
    • Pioglitazone, or
    • An insulin-based treatment.
• For adults with type 2 diabetes who are living with obesity who need further medicines to reach their individualised glycaemic targets and are already taking a GLP-1 receptor agonist or tirzepatide, offer to add:
  • A sulfonylurea or
  • Pioglitazone or
  • An insulin-based treatment.

For adults with type 2 diabetes and chronic kidney disease.

• For adults with type 2 diabetes and chronic kidney disease with an eGFR above 30 mls/min/1.73m, offer:
  • Modified-release metformin and an SGLT2-inhibitor.
    • If metformin is contraindicated or not tolerated, offer an SGLT2-inhibitor as monotherapy.
• For adults with type 2 diabetes and chronic kidney disease with an eGFR between 20 and 30 mls/min/1.73m, offer:
  • Either dapagliflozin or empagliflozin, and 
  • A DPP-4 inhibitor.
• For adults with type 2 diabetes and chronic kidney disease with an eGFR below 20 mls/min/1.73m, consider:
  • A DPP-4 inhibitor.
• If a DPP-4 inhibitor is contraindicated, not tolerated or not effective, consider:
  • Pioglitazone, or
  • Insulin-based treatment. 
• For adults with type 2 diabetes and chronic kidney disease who need further medicines to reach their individualised glycaemic targets:
  • Consider adding a DPP-4 inhibitor.
  • If they are already taking a DPP-4 inhibitor or if a DPP-4 inhibitor is contraindicated, not tolerated or not effective, consider adding:
    • Pioglitazone, or
    • A sulfonylurea (if their eGFR is above 30 ml/min/1.73 m²), or
    • An insulin-based treatment.

For adults with type 2 diabetes frailty.

• For adults with type 2 diabetes frailty:
  • Offer modified-release metformin.
  • Only offer an SGLT-2 inhibitor if the person's level of frailty does not place them at risk of adverse events from such a medication (for example, volume depletion or hypotension).
• If metformin is contraindicated, not tolerated, or not effective, assess whether the person's level of frailty places them at risk of adverse events from SGLT2 inhibitors:
  • If it does not, consider monotherapy with an SGLT2-inhibitor. 
  • If it does, consider monotherapy with a DPP-4 inhibitor.
• For adults with frailty who need further medicines to manage their hyperglycaemia symptoms and reach their individualised glycaemic targets:
  • Consider adding a DPP-4 inhibitor to their current treatment, or
  • If they are already taking a DPP-4 inhibitor or if a DPP-4 inhibitor is contraindicated, not tolerated or is not effective, consider adding one of the following to their current treatment:
    • Pioglitazone or
    • A sulfonylurea or
    • An insulin-based treatment.
• When choosing a treatment for a person with frailty, take into account that sulfonylureas and insulin-based treatments can increase the risk of hypoglycaemia and falls.

• If the person has reached their individualised glycaemic target and weight target, consider continuing any medicines that have contributed to this.
• Consider continuing SGLT-2 inhibitors for their cardiovascular or renal benefits, even if they do not help the person reach their individualised glycaemic targets.
• Stop GLP-1 receptor agonists or tirzepatide if the person becomes underweight (BMI under 18.5 kg/m2).
• Stop GLP-1 receptor agonists or tirzepatide if they do not help the person reach their individualised glycaemic targets and they are not being taken for their cardiovascular benefits.
• Take into account adverse effects from combining medicines (for example, hypoglycaemia).
• Do not offer both a GLP-1 receptor agonist or tirzepatide, and a DPP-4 inhibitor together to treat type 2 diabetes.
• For people on insulin-based treatment, only offer combination therapy with a GLP-1 receptor agonist plus insulin after taking specialist advice, and with ongoing support from a consultant-led multidisciplinary team.
  • Note: if a GLP-1 receptor agonist is added to insulin or an insulin secretagogue (sulfonylurea or meglitinide), consider reducing the dose of the latter agents to reduce the risk of hypoglycaemia. If a DPP-4 inhibitor is being taken, it should be discontinued when starting a GLP-1 receptor agonist, as the combination does not provide additional blood glucose control.

What lifestyle advice should I give to adults with type 2 diabetes?

How should I manage an adult with a suspected hyperglycaemic emergency?

Be aware that diabetic ketoacidosis (DKA) is more common in people with type 1 diabetes, but can occur in people with type 2 diabetes, and may present with a normal or near normal blood glucose level. Hyperosmolar hyperglycaemic state (HHS) typically presents without significant blood or urinary ketones on testing.

• Arrange emergency admission for confirmation of the diagnosis and emergency treatment.
• After the person has recovered from an episode of DKA or HHS:
  • Discuss the precipitating factors that may have led to the episode. Consider the possibility of non-adherence to treatment, particularly if there is a history of recurrent DKA.
  • Provide information and advice about how to manage intercurrent illness and 'sick day rules', to reduce the risk of future episodes. See the section on Managing intercurrent illness for more information.

How should I manage intercurrent illness in an adult with type 2 diabetes?

If an adult with type 2 diabetes is unwell, consider the need to arrange hospital admission or seek specialist advice, depending on clinical judgement, taking into account the person's age, co-morbidities, risk of complications, and the presence of hyperglycaemia and/or ketosis.

• Arrange immediate hospital admission if:
  • There is an immediate risk of diabetic ketoacidosis (DKA), such as moderate ketonuria (2+ on urine dipstick) or ketonaemia (1.5–2.9 mmol/L) with or without hyperglycaemia, and the person cannot eat or drink.
  • There is an immediate risk of hyperosmolar hyperglycaemic state (HHS).
  • There is suspected acute kidney injury (AKI) that cannot be managed in primary care. See the CKS topic on Acute kidney injury for more information.
  • A person treated with insulin does not show signs of clinical improvement with insulin treatment. See the CKS topic on Insulin therapy in type 2 diabetes.
• Consider arranging hospital admission or seeking urgent specialist advice if:
  • The underlying condition is unclear.
  • The person is dehydrated or at risk of dehydration.
  • Vomiting persists beyond 2 hours.
  • The person and their family/carers are unable to keep the blood glucose level above 3.5 mmol/L.
  • The person and their family/carers are exhausted, for example due to repeated night-time waking.
• If admission is not needed and the person can be managed in primary care:
  • Ensure that the person has written contact details of their specialist diabetes team, where appropriate.
  • Assess the person and manage any intercurrent illness(es), as appropriate.
  • Advise on the need to temporarily stop some drug treatments during periods of acute illness. See the section on 'Sick-day rules' for detailed information.
  • Provide the person with clear, individualized advice on 'sick-day rules' to manage diabetes during episodes of intercurrent illness or hyperglycaemia, and reinforce the advice regularly.
    • Advise that intercurrent illness may affect blood glucose control, and there is a risk for worsening hyperglycaemia even if dietary intake is reduced.
  • Ensure the person has sick day foods and drinks supplies readily accessible at home, including:
    • Easily digestible foods and sugary drinks (to provide energy and to prevent further ketosis).
    • Over-the-counter oral rehydration therapy (ORT) sachets (to prevent dehydration).
    • Glucose tablets or oral gel (to prevent hypoglycaemia).
    • Equipment for self-monitoring of blood glucose and ketones (if appropriate). 
    • Additional supplies of insulin (if appropriate).
    • A glucagon kit (if appropriate).
    • Note: see the CKS topic on Insulin therapy in type 2 diabetes for information on blood glucose and ketone monitoring meters, glucose oral gels, and other accessories.

How should I screen for and manage complications in adults with type 2 diabetes?

How should I manage cardiovascular risk in an adult with type 2 diabetes?

What initial information and advice should I offer a child or young person with type 2 diabetes?

Ensure that the child or young person has an individualized care plan, provided by a multidisciplinary paediatric diabetes team.

• Ensure that the child and their family/carers know how to contact the specialist diabetes team and are involved in making decisions about their care.
  • The child or young person may be offered home-based or inpatient management initially, depending on clinical need and family circumstances and wishes.
  • Encourage children and young people and their families/carers to discuss any concerns and raise any questions with their diabetes team
• Ensure that the child and their family/carers are offered a continuing programme of education, which is tailored to their individual needs, including:
  • The need for HbA1c monitoring and treatment targets.
  • The effects of lifestyle and intercurrent illness on blood glucose control.
  • The aims of treatment with antidiabetic drugs and possible adverse effects.
  • Information on how to use their continuous glucose monitoring device (if applicable).
  • The need for regular monitoring for complications of type 2 diabetes, and how to reduce the risk. Note: this will usually be arranged by the paediatric diabetes team at diagnosis and regularly thereafter. If there is any uncertainty, seek specialist advice.
• Provide advice on sources of information and support.
  • Diabetes UK (website available at www.diabetes.org.uk) — a national charity that provides information, support, and advocacy for people with diabetes and their families. It has a confidential helpline (0345 123 2399) and hosts an online community for peer support, as well as a wide range of education and information patient resources.
  • For detailed information on managing other lifestyle and cultural issues, such as driving, fasting, holiday and travel, insurance, and shift work, see the CKS topic on Insulin therapy in type 2 diabetes.
• Assess for anxiety, depression, emotional and behavioural difficulties, and eating disorders, and offer emotional and psychosocial support as needed. See the CKS topics on Depression in children, Conduct disorders in children and young people, and Eating disorders for more information.
  • The Diabetes UK patient resource Diabetes and your emotions may be helpful.
• Advise about sexual health, contraception, and the importance of pre-pregnancy counselling, if appropriate. See the CKS topics on Contraception - assessment and Pre-conception - advice and management for more information.
  • The Diabetes UK patient resource Planning for a pregnancy when you have diabetes may be helpful.
• Offer immunization against influenza (if over the age of 6 months) and pneumococcal infection (if needing oral antidiabetic drugs or insulin). See the CKS topics on Immunizations - seasonal influenza and Immunizations - pneumococcal for more information.
• Measure height and weight, calculate body mass index (BMI), and plot on an appropriate growth chart.
  • Check for normal growth and/or significant changes in weight, as these may reflect changes in blood glucose control.
• Advise the person to always wear or carry some form of diabetes identification, such as a:
  • MedicAlert® bracelet, necklace, or watch (available from www.medicalert.org.uk).
  • Diabetes identity card or wristband (available from www.diabetes.org.uk).

What are the treatment targets for children and young people with type 2 diabetes?

• The recommended HbA1c target level for children and young people with type 2 diabetes is 48 mmol/mol (6.5%) or lower, to minimize the risk of long-term complications.
  • Ensure that the paediatric diabetes team has supported the child or young person and their families/carers to decide upon an individualized lowest achievable HbA1c target, taking into account factors such as daily activities, individual life goals, complications, co-morbidities, and the risk of hypoglycaemia.
    • Support them to safely achieve and maintain their individually agreed HbA1c target level.
    • If the HbA1c level is above the ideal target, explain that any reduction in HbA1c reduces the risk of long-term complications.
  • Ensure that children and young people with type 2 diabetes are offered measurement of their HbA1c level every 3 months.

Which antidiabetic drugs are available for children and young people with type 2 diabetes?

• Antidiabetic drug treatment for children and young people with type 2 diabetes should be initiated by the multidisciplinary paediatric diabetes team.
• Standard-release metformin should be offered from diagnosis to children and young people with type 2 diabetes, and insulin therapy may be needed in some cases. See the CKS topic on Insulin in type 2 diabetes for more information.
• Liraglutide, dulaglutide, or empagliflozin may be used as adjunctive therapy for some children over the age of 10 years.

What lifestyle advice should I give a child or young person with type 2 diabetes?

How should I manage a child or young person with a suspected hyperglycaemic emergency?

Be aware that diabetic ketoacidosis (DKA) is more common in people with type 1 diabetes, but can occur in people with type 2 diabetes, and may present with a normal or near normal blood glucose level. Hyperosmolar hyperglycaemic state (HHS) typically presents without significant blood or urinary ketones on testing.

• Arrange emergency admission to a hospital with acute paediatric facilities, for confirmation of the diagnosis and emergency treatment.
• After the child or young person has recovered from an episode of DKA or HHS:
  • Discuss the precipitating factors that may have led to the episode. Consider the possibility of non-adherence to treatment, particularly if there is a history of recurrent DKA.
  • Provide information and advice about how to manage intercurrent illness and 'sick-day rules', to reduce the risk of future episodes. See the section on Managing intercurrent illness for more information.

How should I manage intercurrent illness in a child or young person with type 2 diabetes?

If a child or young person with type 2 diabetes is unwell, consider the need to arrange hospital admission or seek specialist advice, depending on clinical judgement, taking into account the person's age, co-morbidities, risk of complications, and the presence of hyperglycaemia and/or ketosis.

• Arrange immediate hospital admission if:
  • There is an immediate risk of diabetic ketoacidosis (DKA), such as ketonaemia (1.5–2.9 mmol/L) with or without hyperglycaemia, and the child cannot eat or drink.
  • There is an immediate risk of hyperosmolar hyperglycaemic state (HHS).
  • There is suspected acute kidney injury (AKI) that cannot be managed in primary care. See the CKS topic on Acute kidney injury for more information.
  • A person treated with insulin does not show signs of clinical improvement with insulin treatment. See the CKS topic on Insulin therapy in type 2 diabetes.
• Consider arranging hospital admission or seeking urgent specialist advice if:
  • The underlying condition is unclear.
  • The child is dehydrated or at risk of dehydration.
  • Vomiting persists beyond 2 hours (particularly in young children).
  • The child is younger than 3 years of age or has a co-existing medical condition.
  • The person and their family/carers are unable to keep the blood glucose level above 3.5 mmol/L.
  • The person and their family/carers are exhausted, for example due to repeated night-time waking.
• If admission is not needed and the child or young person can be managed in primary care:
  • Ensure that the person or family/carers has written contact details of their specialist diabetes team.
  • Assess the child and manage any intercurrent illness(es), as appropriate.
  • Provide the person or family/carers with clear, individualized advice on 'sick-day rules' to manage diabetes during episodes of intercurrent illness or hyperglycaemia, and reinforce the advice regularly.
    • Advise that intercurrent illness may affect blood glucose control, and there is a risk for worsening hyperglycaemia even if dietary intake is reduced.
  • Ensure the child has sick day foods and drinks supplies readily accessible at home, including:
    • Easily digestible foods and sugary drinks (to provide energy and to prevent further ketosis).
    • Over-the-counter oral rehydration therapy (ORT) sachets (to prevent dehydration).
    • Glucose tablets or oral gel (to prevent hypoglycaemia).
    • Equipment for monitoring blood glucose and ketones (if appropriate). 
    • Additional supplies of insulin (if appropriate).
    • A glucagon kit (if appropriate).
    • Note: see the CKS topic on Insulin therapy in type 2 diabetes for information on blood glucose and ketone monitoring meters, glucose oral gels, and other accessories.

How should I screen for and manage complications in children and young people with type 2 diabetes?

How should I support the transition from paediatric to adult care services?

• Explain to young people with type 2 diabetes who are preparing for transition to adult services that some aspects of diabetes care will change at transition, such as clinic time and location, and their diabetes specialist team.
  • Be aware that a deterioration in blood glucose control may be seen in young people due to a variety of factors including:
    • Endocrine changes leading to increased insulin resistance.
    • Erratic meal and exercise patterns. See the section on Lifestyle advice for more information.
    • Poor adherence to treatment regimens.
    • Eating disorders. See the CKS topic on Eating disorders for more information.
    • Hazardous and risk-taking behaviours. See the section on Lifestyle advice for more information.
  • The Diabetes UK patient resources Talking to your teenager about diabetes and Transitioning into adult diabetes clinics may be helpful.

Recommended doses

Metformin is currently the only available biguanide.

• For standard-release metformin tablets:
  • 500 mg with breakfast for at least 1 week, then 500 mg with breakfast and evening meal for at least 1 week, then 500 mg with breakfast, lunch, and evening meal thereafter; maximum dose 2 g daily (in divided doses).
• For modified-release metformin tablets:
  • Initially 500 mg once daily, then increased if necessary up to 2 g once daily, dose increased gradually, every 10–15 days, dose to be taken with evening meal.
  • Alternatively, dose increased to 1 g twice daily, dose to be taken with meals, alternative dose only to be used if control not achieved with once daily dose regimen. If control is still not achieved, then change to standard-release tablets.

 [BNF, 2025]

Initiating and monitoring

• Before starting treatment with metformin, check renal function.
  • Do not start metformin treatment if estimated glomerular filtration rate (eGFR) is less than 30 mL/min/1.73 m².
• During treatment with metformin monitor renal function:
  • At least once a year in people with normal renal function.
  • At least twice a year in people with additional risk factors for renal impairment, such as elderly people, or if deterioration in renal function is suspected.
  • Review the dose of metformin if eGFR is less than 45 mL/min/1.73 m².
• Stop treatment with metformin:
  • If eGFR is less than 30 mL/min/1.73 m².
  • In people at risk of tissue hypoxia or sudden deterioration in renal function.
• The risk of low vitamin B12 levels increases with higher metformin dose, longer treatment duration, and in patients with risk factors for vitamin B12 deficiency, including the elderly and people with gastrointestinal disorders such as Crohn’s disease.
  • Test vitamin B12 serum levels if deficiency is suspected (for example, in patients presenting with megaloblastic anaemia or new-onset neuropathy). For more information see the CKS topic on  Anaemia – B12 and folate deficiency.
  • Consider periodic vitamin B12 monitoring in patients with risk factors for vitamin B12 deficiency.

[Metformin and reduced vitamin B12 levels: new advice for monitoring patients at risk. Drug Safety Update.; BNF, 2025; EMC, 2025a]

Contraindications and cautions

• Do not prescribe metformin to people:
  • At risk of lactic acidosis, including people with:
    • Diabetic ketoacidosis.
    • Estimated glomerular filtration rate (eGFR) less than 30 mL/minute/1.73 m².
    • Risk of acute kidney injury, such as dehydration, prolonged fasting, severe infection, or shock.
    • Conditions that may cause tissue hypoxia, such as cardiac or respiratory failure, recent myocardial infarction, or shock.
    • Hepatic insufficiency, acute alcohol intoxication.
• Prescribe metformin with caution to people with:
  • Potential impaired renal function, for example use of concomitant nephrotoxic drugs, or in elderly people (due to the increased risk of lactic acidosis).

[BNF, 2025; EMC, 2025a]

Adverse effects

• Adverse effects of metformin include:
  • Gastrointestinal — nausea, vomiting, diarrhoea, abdominal pain, loss of appetite, taste disturbance. These are common, occur most frequently during initiation of treatment, and resolve spontaneously in most cases. 
  • Lactic acidosis — this is rare but potentially life-threatening.
    • It has an insidious onset with non-specific signs and symptoms, such as abdominal pain, anorexia, hypothermia, lethargy, nausea, respiratory distress, and vomiting.
    • Stop metformin treatment if estimated glomerular filtration rate (eGFR) is less than 30 mL/min/1.73 m².
  • Vitamin B12 deficiency — reduced vitamin B12 absorption has been reported during long-term use, at higher doses, and in people with risk factors for vitamin B12 deficiency. If this is suspected, monitor serum levels. See the CKS topic on Anaemia - B12 and folate deficiency for more information.
  • Skin reactions including erythema, pruritus, and urticaria (rare). 

[Metformin and reduced vitamin B12 levels: new advice for monitoring patients at risk. Drug Safety Update.; BNF, 2025; EMC, 2025a]

Drug interactions

• Drug interactions associated with metformin include:
  • Alcohol — increased risk of lactic acidosis. In addition, the hypoglycaemic effect of metformin may be enhanced by alcohol. Concurrent use is not recommended.
  • Beta-blockers — the warning signs of hypoglycaemia (such as tremor) may be masked during concurrent treatment.
  • Ketotifen — platelet count may be depressed when metformin is given with ketotifen. Avoid concurrent use. 
  • Topiramate — plasma concentration of metformin may be increased by topiramate.
  • Other antidiabetic drugs — caution is advised when metformin is used in combination (due to the risk of hypoglycaemia).
• In addition:
  • The blood glucose-lowering effects of metformin may be enhanced by:
    • Angiotensin-converting enzyme (ACE) inhibitors.
    • Anabolic steroids.
    • Monoamine oxidase inhibitors (MAOIs).
    • Testosterone.
  • The blood glucose-lowering effects of metformin may be antagonized by:
    • Corticosteroids.
    • Diuretics (thiazide and related, and loop). 
    • Oestrogens and progestogens.
  • Metformin is a substrate of both organic cation transporters, OCT1 and OCT2. Co-administration of metformin with:
    • Inhibitors of OCT1 (such as verapamil) may reduce efficacy of metformin.
    • Inducers of OCT1 (such as rifampicin) may increase gastrointestinal absorption and efficacy of metformin.
    • Inhibitors of OCT2 (such as cimetidine, dolutegravir, ranolazine, trimethoprim, vandetanib, isavuconazole) may decrease the renal elimination of metformin and thus lead to an increase in metformin plasma concentration.
    • Inhibitors of both OCT1 and OCT2 (such as crizotinib, olaparib) may alter efficacy and renal elimination of metformin.
  • Caution is therefore advised, especially in patients with renal impairment, when these drugs are co-administered with metformin, as metformin plasma concentration may increase. If needed, dose adjustment of metformin may be considered as OCT inhibitors/inducers may alter the efficacy of metformin.

[BNF, 2025; EMC, 2025a]

Recommended doses

There are currently five DPP-4 inhibitors available in the UK.

• For adults over 18 years of age:
  • Alogliptin: 25 mg once daily.
  • Linagliptin: 5 mg once daily.
  • Sitagliptin: 100 mg once daily.
  • Saxagliptin: 5 mg once daily.
  • Vildagliptin: 50 mg twice daily. When used in dual combination with a sulfonylurea, reduce to 50 mg once daily in the morning.
• In people with renal impairment:
  • Alogliptin: 12.5 mg once daily if creatinine clearance (CrCl) is 30–50 mL/minute. Reduce to 6.25 mg once daily if CrCl is less than 30 mL/minute.
  • Linagliptin: no dose adjustment is required.
  • Saxagliptin: 2.5 mg once daily in moderate to severe renal impairment.
  • Sitagliptin: 50 mg once daily if eGFR is 30–45 mL/minute/1.73 m². Reduce to 25 mg once daily if eGFR is less than 30 mL/minute/1.73 m².
  • Vildagliptin: 50 mg once daily if CrCl is less than 50 mL/minute.

[BNF, 2025]

Initiating and monitoring

• Before starting treatment with saxagliptin, sitagliptin, vildagliptin, or alogliptin:
  • Check liver and kidney function. See the section on Contraindications and cautions for more information.
• During treatment with:
  • Vildagliptin: monitor liver function at 3-monthly intervals during the first year, and periodically thereafter.
    • If the person develops increased transaminase levels, repeat liver function tests (LFTs) and monitor until results normalize. 
  • Alogliptin, saxagliptin, sitagliptin: monitor renal function periodically.

 [BNF, 2025]

Contraindication and cautions

• Do not prescribe a DPP-4 inhibitor to people with:
  • Ketoacidosis.
  • Hepatic impairment — avoid vildagliptin; avoid saxagliptin and alogliptin if severe hepatic impairment.
  • Heart failure — avoid vildagliptin if severe heart failure; avoid alogliptin if moderate-to-severe heart failure.
• Prescribe a DPP-4 inhibitor with caution to people:
  • With renal impairment — use saxagliptin with caution in severe renal impairment.
  • With hepatic impairment — use saxagliptin with caution in moderate hepatic impairment.
  • With a history of pancreatitis (alogliptin, saxagliptin, vildagliptin).
  • Heart failure — use saxagliptin with caution if moderate-to-severe heart failure.
  • Who are elderly — use saxagliptin with caution.

[BNF, 2025]

Adverse effects

Possible adverse effects of DPP-4 inhibitors include:

• Gastrointestinal — constipation, vomiting, nausea, diarrhoea, dyspepsia, gastritis, and gastro-oesophageal reflux (common). 
• Acute pancreatitis (uncommon).
  • Advise to seek urgent medical assessment if the person develops jaundice or other signs suggestive of liver dysfunction (such as nausea, vomiting, abdominal pain, fatigue, and dark urine), and stop treatment.
• Hepatic — hepatitis and hepatic failure (with vildagliptin and alogliptin, rare).
• Nervous system — headache, dizziness, and tremor (common with sitagliptin, saxagliptin, vildagliptin, and alogliptin).
• Skin — pruritus, angioedema, rash, urticaria, cutaneous vasculitis, bullous pemphigoid (with alogiptin) and Stevens-Johnson syndrome.
• Musculoskeletal — back pain, arthralgia, myalgia, and arthropathy (with sitagliptin and saxagliptin).
• Infections — increased risk with saxagliptin, alogliptin, and vildagliptin.
• Hypersensitivity reactions (including anaphylaxis) have been reported with sitagliptin, saxagliptin, linagliptin, and alogliptin.
• Other adverse effects include:
  • For sitagliptin: interstitial lung disease, impaired renal function, thrombocytopaenia, and acute renal failure.
  • For saxagliptin: erectile dysfunction, peripheral oedema, dyslipidaemia, and hypertriglyceridaemia.
  • For linagliptin: nasopharyngitis, cough, and increased amylase levels.

 [BNF, 2025]

Drug interactions

• Possible drug interactions associated with DPP-4 inhibitors include: 
  • Beta-blockers — the warning signs of hypoglycaemia (such as tremor) may be masked during concurrent treatment.
  • Angiotensin-converting enzyme (ACE) inhibitors — there may be an increased risk of angioedema in people taking vildagliptin and ACE-inhibitors concomitantly.
  • Digoxin — sitagliptin increases plasma concentration of digoxin. No dose adjustment of digoxin is recommended, however monitor people at risk of digoxin toxicity.
  • Ketoconazole — plasma concentration of saxagliptin may be increased by ketoconazole.
  • Rifampicin — effects of linagliptin are possibly reduced by rifampicin.
  • Other antidiabetic drugs — the dose of concomitant sulfonylurea may need to be reduced due to an increased risk of hypoglycaemia.
• In addition:
  • The blood glucose-lowering effects of DPP-4 inhibitors may be enhanced by: 
    • Alcohol.
    • Anabolic steroids.
    • Monoamine oxidase inhibitors (MAOIs).
    • Testosterone. 
  • The blood glucose-lowering effects of DPP-4 inhibitors may be antagonized by: 
    • Corticosteroids. 
    • Diuretics (thiazide and related, and loop). 
    • Oestrogens and progestogens.

 [BNF, 2025]

Recommended dose

• Pioglitazone is the only thiazolidinedione currently available in the UK.
  • The recommended dose is 15–30 mg once daily, increased to 45 mg once daily, according to response. In elderly people, prescribe 15 mg once daily initially, and increase the dose gradually.

 [BNF, 2025]

Initiating and monitoring

• Before starting treatment with pioglitazone:
  • Monitor liver function tests (LFTs).
    • If alanine aminotransferase (ALT) is more than 2.5 times the upper limit of normal, or there is any other evidence of liver disease, do not start treatment.
  • Assess the risk of heart failure and bone fracture. See the CKS topics on Heart failure and Osteoporosis - prevention of fragility fractures for more information.
  • Assess the risk of bladder cancer. See the CKS topic on Urological cancers - recognition and referral for more information. Risk factors include:
    • Increasing age.
    • Current or past history of smoking.
    • Exposure to some occupational or chemotherapy drugs, such as cyclophosphamide.
    • Previous radiation therapy to the pelvic region.
• Following initiation of treatment with pioglitazone:
  • Monitor LFTs periodically, based on clinical judgement.
  • Monitor for signs and symptoms of heart failure, such as weight gain or oedema. 
    • Stop pioglitazone if any deterioration in cardiac function is seen.
  • Assess the safety and efficacy of pioglitazone 3–6 months after treatment is initiated, and regularly thereafter.
    • Stop pioglitazone in people who do not respond adequately to treatment.
    • Advise the person to seek urgent medical assessment if any symptoms or signs of bladder cancer develop. See the CKS topic on Urological cancers - recognition and referral for more information.

[MHRA, 2014; BNF, 2025]

Contraindications and cautions

• Do not prescribe pioglitazone to people with:
  • Heart failure or a history of heart failure.
  • Uninvestigated macroscopic haematuria.
  • Previous or active bladder cancer.
  • Hepatic impairment.
• Prescribe pioglitazone with caution to people:
  • Who are elderly — increased risk of bladder cancer, heart failure, and fracture.
  • Who also use insulin — increased risk of heart failure.
  • Risk factors for bladder cancer. See the CKS topic on Urological cancers - recognition and referral.
  • Risk factors for heart failure (such as previous myocardial infarction, cardiovascular disease). See the CKS topic on Heart failure - chronic for more information.
  • Risk factors for bone fracture. See the CKS topic on Osteoporosis - prevention of fragility fractures for more information.

[MHRA, 2014; BNF, 2025]

Adverse effects

Possible adverse effects of pioglitazone include:

• Numbness, visual impairment, weight increase, insomnia.
• Increased risk of bone fractures.
• Increased risk of infection.
• Bladder cancer.
• Hepatic impairment (rare) — stop pioglitazone if jaundice occurs. Seek immediate medical advice if symptoms such as nausea, vomiting, abdominal pain, fatigue, and dark urine develop.

[MHRA, 2014; BNF, 2025]

Drug interactions

• Potential drug interactions associated with pioglitazone include:
  • Beta-blockers — the warning signs of hypoglycaemia (such as tremor) may be masked when pioglitazone is given with a beta-blocker.
  • Gemfibrozil — can significantly increase the plasma concentration of pioglitazone. Consider reducing the dose of pioglitazone.
  • Ketoconazole — the plasma concentration of pioglitazone may be increased by ketoconazole.
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) — post marketing cases of peripheral oedema and cardiac failure have been reported. Discontinue pioglitazone if any deterioration in cardiac status occurs.
  • Liver enzyme-inducing drugs — rifampicin can significantly reduce the plasma concentration of pioglitazone (and the pioglitazone dose may need to be increased). Closely monitor blood glucose control during concurrent use of pioglitazone and other liver enzyme-inducers, such as phenytoin, carbamazepine, and St John's wort, as these may also affect the plasma concentration of pioglitazone.
  • Other antidiabetic drugs — people taking pioglitazone in dual or triple oral therapy with a sulfonylurea may be at increased risk of hypoglycaemia. It may be necessary to reduce the dose of the sulfonylurea.
• In addition: 
  • The blood glucose-lowering effects of pioglitazone may be enhanced by: 
    • Alcohol.
    • Anabolic steroids. 
    • Monoamine oxidase inhibitors (MAOIs).
    • Testosterone. 
  • The blood glucose-lowering effects of pioglitazone may be antagonized by: 
    • Corticosteroids. 
    • Diuretics (thiazide and related, and loop). 
    • Oestrogens and progestogens.

[BNF, 2025]

Recommended doses

There are currently four sulfonylureas available for use in adults in the UK.

• The recommended doses are:
  • Gliclazide:
    • Standard-release tablets: 40–80 mg daily, dose adjusted according to response; increase up to 160 mg once daily with breakfast. Doses higher than 160 mg should be divided, maximum dose 320 mg daily.
    • Modified-release tablets: 30 mg daily with breakfast, dose adjusted according to response every 4 weeks, or after 2 weeks if no decrease in blood glucose level. The maximum dose is 120 mg daily.
  • Glimepiride:
    • 1 mg daily taken shortly before or with first main meal, adjusted according to response in 1 mg steps at 1–2 week intervals. The usual maximum dose is 4 mg daily (in exceptional circumstances, up to 6 mg daily may be used).
  • Glipizide:
    • 2.5–5 mg daily taken shortly before breakfast or lunch, adjusted according to response. Doses of up to 15 mg may be given as a single dose, higher doses should be divided. The maximum dose is 20 mg daily.
  • Tolbutamide:
    • 0.5–1.5 g daily in divided doses (with, or immediately after, meals), or as a single dose (with, or immediately after, breakfast). The maximum dose is 2 g daily.

 [BNF, 2025]

Contraindications and cautions

• Do not prescribe a sulfonylurea to people with:
  • Acute porphyria (glibenclamide, gliclazide, and tolbutamide).
  • Ketoacidosis.
  • Severe renal impairment.
    • If necessary, tolbutamide (a short-acting sulfonylurea) and gliclazide (which is principally metabolized in the liver) can be used at the lowest dose to provide blood glucose control.
  • Severe hepatic impairment — increased risk of hypoglycaemia.
• Prescribe a sulfonylurea with caution in people:
  • With mild-to-moderate renal impairment — increased risk of hypoglycaemia.
  • With mild-to-moderate hepatic impairment — increased risk of hypoglycaemia (with glipizide). Manufacturer advises initial dose of glipizide of 2.5 mg daily with low maintenance dose.
  • Who are obese — can increase weight gain.
  • Who are elderly — glibenclamide or glimepiride (long-acting sulfonylureas) are associated with a greater risk of prolonged hypoglycaemia in older people.
  • With G6PD deficiency.

 [BNF, 2025]

Adverse effects

Adverse effects of sulfonylureas may include:

• Gastrointestinal — abdominal pain, nausea, vomiting, diarrhoea, and constipation.
• Hepatic impairment.
• Skin — rash, pruritus, urticaria, angioedema, erythema, allergic dermatitis (usually in the first 6–8 weeks of treatment), photosensitivity reaction, Stevens-Johnson syndrome (glibenclamide).
• Blood — leucopenia, thrombocytopenia, agranulocytosis, pancytopenia, haemolytic anaemia, and aplastic anaemia (tolbutamide).
• Other:
  • Hypoglycaemia.
  • Hyponatraemia (gliclazide, glipizide).
  • Dizziness, drowsiness, tremor (glipizide).

 [BNF, 2025]

What drug interactions are associated with sulfonylureas?

• Possible drug interactions associated with sulfonylureas include:
  • Beta-blockers — the warning signs of hypoglycaemia (such as tremor) may be masked when a sulfonylurea is given with a beta-blocker.
  • Colesevelam — the absorption of glibenclamide, glimepiride, and glipizide may be reduced by colesevelam.
    • The manufacturer of glimepiride advises that it is taken at least 4 hours before colesevelam. 
    • Other drugs should be taken at least 4 hours before or after colesevelam, to reduce possible interference with absorption.
  • Fibrates — there may be improved glucose tolerance and an additive effect when a sulfonylurea is given with a fibrate.
  • Fluconazole — the plasma concentration of sulfonylureas may be increased by fluconazole.
  • Fluvastatin — the plasma concentration of glibenclamide may be increased by fluvastatin.
  • Norfloxacin — the effects of glibenclamide may be enhanced by norfloxacin.
  • Phenytoin and fosphenytoin — tolbutamide transiently increases plasma concentration of these drugs (possibility of toxicity).
  • Rifamycins — the metabolism of sulfonylureas may be accelerated by rifamycins (reduced effect).
  • Ritonavir — the plasma concentration of tolbutamide may be increased by ritonavir.
  • St John’s wort — can cause poor blood glucose control when taken in combination with gliclazide.
  • Topiramate — the plasma concentration of glibenclamide may be reduced by topiramate.
  • Trimethoprim — the effects of sulfonylureas may be enhanced by trimethoprim.
  • Voriconazole and ketoconazole — the plasma concentration of sulfonylureas may be increased by voriconazole, and plasma concentration of tolbutamide may be increased by ketoconazole.
  • Other antidiabetic drugs — the dose of the sulfonylurea (and in some cases the concomitant antidiabetic drug) may need to be reduced, to reduce the risk of hypoglycaemia.
• In addition:
  • The blood glucose-lowering effects of sulfonylureas may be enhanced by: 
    • Alcohol.
    • Anabolic steroids.
    • Angiotensin-converting enzyme (ACE) inhibitors.
    • Chloramphenicol.
    • Cimetidine.
    • Coumarins.
    • Disopyramide (enhances hypoglycaemic effect of gliclazide).
    • Leflunomide (enhances hypoglycaemic effect of tolbutamide).
    • Monoamine oxidase inhibitors (MAOIs).
    • Miconazole (avoid concurrent use with gliclazide and glipizide).
    • Nonsteroidal anti-inflammatory drugs.
    • Testosterone. 
    • Tetracyclines.
    • Trimethoprim (rare).
  • The blood glucose-lowering effects of sulfonylureas may be antagonized by: 
    • Corticosteroids. 
    • Diuretics (thiazide and related, and loop). 
    • Oestrogens and progestogens.
    • Phenothiazines.

 [BNF, 2025]

Before initiating SGLT-2 inhibitors

• SGLT-2 inhibitors have been associated with severe and life-threatening diabetic ketoacidosis.

[EMC, 2025b]

Recommended doses

There are four SGLT-2 inhibitors available in the UK. The recommended doses are:

• Canagliflozin
  • Recommended starting dose is 100 mg once daily, increased to 300 mg once daily if needed, dose to be taken preferably before breakfast.
• Dapagliflozin
  • Recommended dose is 10 mg once daily.
• Empagliflozin
  • Recommended starting dose is 10 mg once daily, increased to 25 mg once daily if needed and tolerated.
• Ertuglifozin
  • Recommended starting dose is 5 mg once daily, increased to 15 mg once daily if needed and tolerated, dose to be taken in the morning.

 [BNF, 2025]

Contraindications and cautions

•  Do not prescribe an SGLT-2 inhibitor to people with:
  • Diabetic ketoacidosis (DKA) — serious and potentially life-threatening cases of DKA have been reported in people taking SGLT-2 inhibitors. Advise to stop treatment immediately and seek medical advice if any clinical features of DKA develop.
  • Moderate-to-severe renal impairment — in general, avoid initiation if estimated glomerular filtration rate (eGFR) is less than 60 mL/min/1.73 m²; avoid continuation if eGFR is less than 45 mL/min/1.73 m^2.
    • Note: dapagliflozin and empagliflozin are licensed for use in chronic kidney disease, but should not be initiated unless the person has an estimated glomerular filtration rate of:
      • 20 ml/min/1.73 m2 to less than 45 ml/min/1.73 m² or
      • 45 ml/min/1.73 m2 to 90 ml/min/1.73 m² and either a urine albumin-to-creatinine ratio of 22.6 mg/mmol or more, or type 2 diabetes.
    •  The glucose-lowering efficacy of both dapagliflozin and empagliflozin is reduced when eGFR is less than 45 mL/min/1.73m². For more information, see the section on Diabetic kidney disease.  
  • Specifically relating to canagliflozin  
    • In people with an eGFR 60 mL/min/1.73 m² or higher canagliflozin should be initiated at 100 mg. In patients tolerating 100 mg and requiring additional glycaemic control, the dose can be increased to 300 mg.
    • In people with an eGFR between 30–60 mL/min/1.73 m² canagliflozin should be initiated at 100 mg and maintained at this dose. 
    • In people with an eGFR less than 30 mL/min/1.73 m² canagliflozin should not be initiated. However, for those people already taking canagliflozin they can be maintained on 100mg.          
    • Monitor renal function at least twice yearly in the presence of moderate renal impairment. More regular monitoring or modification of therapy may be required if there is a trend in reduction of eGFR, the addition of other medication which may reduce renal function, or evidence of volume depletion (for example, postural dizziness or hypotension).
  • Specifically relating to empagliflozin:
    • In people who have an eGFR below 60 ml/min/1.73 m² the daily dose of empagliflozin is limited to 10 mg.
    • Empagliflozin is not recommended fort people with type 2 diabetes when eGFR is below 20 ml/min/1.73 m².
    • Empagliflozin should not be used in patients with end-stage renal disease or in patients on haemodialysis. 
    • Renal function should be monitored prior to empagliflozin initiation and periodically during treatment, this is, at least yearly and prior to initiation of any concomitant medicinal product that may have a negative impact on renal function.
  • Severe hepatic impairment — manufacturer advises to avoid canagliflozin, empagliflozin, and ertugliflozin.
  • Increasing age — avoid empagliflozin if aged over 85 years, as risk of volume depletion.
  • Active foot disease (such as skin ulceration, osteomyelitis, or gangrene) — possible increased risk of lower limb amputation (mainly toes) with canagliflozin. Advise to stop treatment if signs of a foot complication develop, such as skin ulceration, discolouration, infection, or new pain/tenderness, and seek urgent medical assessment.
• Prescribe an SGLT-2 inhibitor with caution in people with:
  • Factors that may predispose to ketoacidosis.
  • Severe hepatic impairment — manufacturer advises caution with dapagliflozin and to start at lower 5 mg once daily dose; increase to 10 mg once daily if tolerated.
  • History of foot ulcer, peripheral arterial disease, or lower limb amputation — increased risk of lower limb amputation (mainly toes) with canagliflozin. Advise to stop treatment if signs of a foot complication such as skin ulceration, discolouration, infection, or new pain/tenderness, and seek urgent medical assessment.
  • Increasing age, hypotension — risk of volume depletion.
  • Complicated urinary tract infection — consider temporarily stopping empagliflozin and canagliflozin treatment.
  • Lithium — renal excretion of lithium may be increased by empagliflozin, reducing serum lithium levels. Monitor levels frequently after starting empagliflozin and after dose changes.

[MHRA, 2016; MHRA, 2017; NICE, 2023g; EMC, 2024a; BNF, 2025; EMC, 2025b; EMC, 2025c; NICE, 2025]

Adverse effects

Possible adverse effects of SGLT-2 inhibitors include:

• Vulvovaginitis, balanoposthitis, urinary tract infection (UTI) or urosepsis — cases of phimosis/acquired phimosis have been reported concurrent with genital infections and in some cases, circumcision was required.
• Fournier’s gangrene — this is a rare but potentially life-threatening necrotizing fasciitis of the genitalia and perineum (predominantly in men). May present as severe pain or tenderness, erythema, and swelling in the genital or perineal area, with fever or malaise. Advise to stop the SGLT-2 inhibitor immediately and seek immediate medical assessment if suspected.
• Complicated UTIs including pyelonephritis and urosepsis have been reported in patients treated with canagliflozin — consider temporarily stopping treatment if this occurs. Tubulointerstitial nephritis has been reported in people taking empagliflozin/metformin and dapagliflozin. 
• Constipation, nausea, thirst, dyslipidaemia, hypotension, syncope.
• Lower limb amputation (canagliflozin).
• Renal impairment.

[MHRA, 2019; EMC, 2024b; BNF, 2025; EMC, 2025d]

Drug interactions

• Possible drug interactions with SGLT-2 inhibitors include:
  • Thiazide and loop diuretics — additive effect of thiazide and loop diuretics and may increase the risk of dehydration and hypotension.
  • Insulin and insulin secretagogues (such as sulphonylureas) — cause hypoglycaemia. Therefore, a lower dose of insulin or an insulin secretagogue (such as a sulfonylurea) may be required to reduce the risk of hypoglycaemia.
  • Enzyme-inducers (such as St John's wort, rifampicin, barbiturates, phenytoin, carbamazepine, ritonavir, efavirenz) — may decrease the efficacy of canagliflozin.
  • Digoxin — risk of digoxin toxicity, monitored appropriately.
  • Dabigatran — dabigatran concentrations may be increased with canagliflozin. Monitor for signs of bleeding or anaemia when dabigatran is combined with canagliflozin.
  • Cholestyramine — may potentially reduce canagliflozin exposure. Dosing of canagliflozin should occur at least 1 hour before or 4–6 hours after administration of a bile acid sequestrant, to minimize possible interference with absorption.
  • Lithium —  dapagliflozin may increase renal lithium excretion and decrease blood lithium levels.

[EMC, 2024a; BNF, 2025; EMC, 2025b; EMC, 2025c]

Recommended doses

There are currently five GLP-1 receptor agonists available in the UK, which are self-administered by subcutaneous injection in the thigh, abdomen, or upper arm, rotating the injection sites from one injection to the next.

• The recommended doses are:
  • For exenatide:
    • Standard-release formulation: 5 micrograms twice daily, increased if necessary, after at least 1 month to a maximum dose of 10 micrograms twice daily. It should be administered within 1 hour before two main meals (at least 6 hours apart). It should not be administered after a meal.
    • Modified-release formulation: 2 mg once weekly on the same day each week (at any time, with or without meals). The day of weekly administration can be changed if necessary, as long as the next dose is administered at least 24 hours later. 
  • For liraglutide:
    • 0.6 mg once daily, increased after at least 1 week to 1.2 mg once daily. This can be further increased if necessary, after an interval of at least 1 week to a maximum dose of 1.8 mg once daily.
  • For dulaglutide:
    • 0.75 mg once weekly as monotherapy; 1.5 mg once weekly as add-on therapy.
  • For semaglutide:
    • 0.25 mg once weekly for 4 weeks, then 0.5 mg once weekly for at least 4 weeks, then increased to 1 mg once weekly if needed.
  • For tirzepatide:
    • 2.5 mg once weekly for 4 weeks, then 5 mg once weekly for at least 4 weeks, then increased if necessary up to 15 mg once weekly, with doses increased in steps of 2.5 mg at intervals of at least 4 weeks.

 [BNF, 2025]

Contraindications and cautions

• Do not offer both a GLP-1 receptor agonist or tirzepatide and a DPP-4 inhibitor together to treat type 2 diabetes.
• Do not prescribe a GLP-1 receptor agonist to people with:
  • Ketoacidosis.
  • Pancreatitis.
  • Renal impairment:
    • Avoid exenatide standard-release and liraglutide injection if estimated glomerular filtration rate (eGFR) is less than 30 mL/min/1.73 m².
    • Avoid exenatide modified-release injection if eGFR is less than 50 mL/min/1.73 m².
    • Avoid liraglutide and semaglutide in end-stage renal disease.
  • Severe hepatic impairment — avoid liraglutide.
  • Severe gastrointestinal disease — avoid exenatide, liraglutide (for example if diabetic gastroparesis or inflammatory bowel disease), lixisenatide, and dulaglutide.
• Prescribe a GLP-1 receptor agonist with caution in:
  • People with a history of pancreatitis — discontinue if symptoms of acute pancreatitis occur.
  • People with renal impairment — if eGFR is 30–50 mL/min/1.73 m² use standard-release exenatide and lixisenatide with caution.
  • People with hepatic impairment — caution with semaglutide.
  • Elderly people — may cause weight loss (exenatide).
  • Women of childbearing potential as there is a lack of safety data available for these medications. For more information see the CKS topic on Pre-conception -advice and management. 
  • Women who are breastfeeding. 
  • People with severe heart failure — use liraglutide and semaglutide with caution.
  • People with thyroid disease — history of medullary thyroid cancer or multiple endocrine neoplasia (MEN) type 2 disease (for liraglutide).
  • People with retinopathy — use semaglutide and tirzepatide with caution.

[EMC, 2024c; EMC, 2024d; BNF, 2025; EMC, 2025e; EMC, 2025f; EMC, 2025g; CoSRH, 2025]

Adverse effects

Possible adverse effects of GLP-1 receptor agonists include:

• Acute pancreatitis (rare) — advise the person to seek urgent medical advice if symptoms such as severe upper abdominal pain, nausea, and/or vomiting develop. Advise to discontinue treatment if pancreatitis is suspected.
• Gastrointestinal — decreased appetite, altered taste, nausea, vomiting, dyspepsia, burping, gastro-oesophageal reflux, constipation, diarrhoea, gallbladder disorders (liraglutide), delayed gastric emptying (lixisenatide, semaglutide). Exenatide and tirzepatide have been noted to cause cholecystitis and cholelithiasis as rare adverse effects. Semagutide has been noted to include intestinal obstruction as an adverse reaction of unknown frequency.
• Headache, dizziness, fatigue, drowsiness, alopecia, hyperhidrosis.
• Renal impairment (exenatide and liraglutide).
• Atrioventricular block, sinus tachycardia, delayed gastric emptying (dulaglutide).
• Skin reactions including rash, angioedema, cutaneous amyloidosis (liraglutide), urticaria, and pruritus.
• Increased risk of non-arteritic anterior ischaemic optic neuropathy during treatment with semaglutide — patients reporting a sudden loss of vision should be urgently referred for ophthalmological examination.

[EMC, 2024c; EMC, 2024d; BNF, 2025; EMC, 2025e; EMC, 2025f; EMC, 2025g]

Drug interactions

• For tirzepatide and oral contraceptives.
  • Delayed gastric emptying for tirzepatide may have a greater impact on the absorption of oral contraceptives compared to other GLP-1RA medicines. However, due to limited information available about the effect of tirzepatide on the pharmacokinetics and efficacy of oral contraceptives in individuals with obesity or who are overweight, reduced efficacy cannot be excluded.
  • Since this reduced efficacy of oral contraceptives cannot be excluded, it is advised that people taking tirzepatide should switch to a non-oral contraceptive method or add a barrier method of contraception when the drug is started (for 4 weeks) and after each dose escalation (for 4 weeks).
  • No dose adjustment of oral contraceptives is required in women with a normal BMI.
• Possible drug interactions associated with GLP-1 receptor agonists include:
• • Beta-blockers — the warning signs of hypoglycaemia (such as tremor) may be masked during concurrent treatment with a beta-blocker.
  • Paracetamol — lixisenatide possibly reduces the absorption of paracetamol when given 1–4 hours before paracetamol.
  • Warfarin — exenatide and liraglutide possibly enhance the anticoagulant effect of warfarin. Monitor the international normalized ratio (INR) during concurrent treatment with warfarin. Also consider monitoring INR at the time of initiation or stopping of lixisenatide treatment.
  • Other orally administered drugs — may need to be taken at least 1 hour before or 4 hours after lixisenatide or exenatide injection or taken with a meal when lixisenatide is not administered, to minimize possible interference with absorption.
  • Other antidiabetic drugs — due to the increased risk of hypoglycaemia, the dose of concomitant sulfonylurea may need to be reduced.
• In addition:
  • The blood glucose-lowering effects of GLP-1 receptor agonists may be enhanced by:
    • Alcohol.
    • Anabolic steroids.
    • Disopyramide.
    • Monoamine oxidase inhibitors (MAOIs).
    • Testosterone.
  • The blood glucose-lowering effects of GLP-1 receptor agonists may be antagonized by:
    • Corticosteroids.
    • Diuretics (thiazide and related, and loop).
    • Oestrogens and progestogens.

[EMC, 2024c; EMC, 2024d; BNF, 2025; EMC, 2025e; EMC, 2025f; EMC, 2025g]

Recommended doses

Finerenone is recommended as an option for treating stage 3 and 4 chronic kidney disease (with albuminuria) associated with type 2 diabetes in adults. 

• Serum potassium and estimated glomerular filtration rate (eGFR) have to be measured to determine if finerenone treatment can be initiated and to determine the starting dose.
  • If serum potassium ≤ 4.8 mmol/L, finerenone treatment can be initiated.
  • If serum potassium > 4.8 to 5.0 mmol/L, initiation of finerenone treatment may be considered with additional serum potassium monitoring within the first 4 weeks, based on the person’s comorbidities and subsequent serum potassium levels.
  • If serum potassium > 5.0 mmol/L, finerenone treatment should not be initiated.
• Additionally, finerenone can only be initiated if the person has an estimated glomerular filtration rate (eGFR) of 25 ml/min/1.73 m² or more.
  • If the person's eGFR is between 25 and 60 ml/min/1.73 m² the starting dose should be 10 mg finerenone. 
  • In people who have an eGFR > 60 ml/min/1.73 m² the starting dose should be 20 mg finerenone. 

[EMC, 2023; BNF, 2025]

Contraindications and cautions

• Do not prescribe finerenone to people with:
  • An eGFR of less than 25 mL/min/1.73m².
  • Serum potassium level greater than 5.0 mmol/L.
  • Severe hepatic impairment.

[EMC, 2023; BNF, 2025]

Adverse effects

• Adverse effects of finerenone include:
  • Electrolyte imbalance - eGFR and serum potassium should be measured 4 weeks after initiation to determine whether the starting dose can be increased to the recommended daily dose of 20 mg. Serum potassium should be assessed periodically, dependent on clinical judgement and the trends in serum potassium for the individual. 
  • Hypotension.
  • Pruritus. 

[EMC, 2023; BNF, 2025]

Drug interactions

• Finerenone should not be given concomitantly with:
  • Potassium-sparing diuretics (such as amiloride and triamterene).
  • Mineralocorticoid receptor antagonists (such as eplerenone and sprinolactone).
  • Rifampicin.
  • Itraconazole.
  • Clarithromycin.
  • Other strong CYP3A4 inducers (such as ketoconazole, carbamazepine, phenytoin, phenobarbital, and St John's wort). 
• Finerenone should be used with caution and potassium monitored when taken concomitantly with:
  • Potassium supplements.
  • Trimethoprim or trimethoprim with sulfamethoxazole. Temporary discontinuation of finerenone may be necessary.
  • Erythromycin.
  • Antihypertensive medications, as the risk of hypotension is possible. Blood pressure monitoring is recommended in these people. 

[EMC, 2023; BNF, 2025]