3.2 The GLP-1s

Effectiveness in weight loss

In clinical trials, GLP-1 drugs showed up to 16-22% weight loss at the highest dose after 68-72 weeks.

The trial intervention was not a stand-alone GLP-1 but a combination of the drug with a reduced calorie diet, increased physical activity and counselling support  (which typically should take place weekly for the first 12 weeks). Rapid weight loss was followed by a rebound when people stopped taking the GLP-1 — the majority regained the weight they had lost.

Semaglutide, liraglutide, orforglipton and tirzepatide are licensed for weight loss in people who have obesity, or who are overweight and have at least one weight-related health condition.

It is important to distinguish between licensed indications and NICE guidance that governs the use of GLP-1s in the NHS. NICE recommends a maximum of two years’  use and within a specialist weight management service providing multidisciplinary support of overweight or obesity, and that the person:

Has at least one weight-related comorbidity (e.g. hypertension, dyslipidaemia, obstructive sleep apnoea, cardiovascular disease, prediabetes or type 2 diabetes mellitus) and:

• A body mass index (BMI) of at least 35.0, or
• A BMI of 30.0-34.9 and meets the criteria for referral to specialist weight management services in NICE’s Guideline on Obesity: Identification, Assessment and Management.

NICE also recommends that clinicians use lower BMI thresholds (reduced by 2.5) for people from South Asian, Chinese, other Asian, Middle Eastern, Black African or African-Caribbean family backgrounds to reflect their greater risk of obesity-related illness.

Details of the licensed indications for injections are listed in Table 1.

Licensed indications for oral formats are similar to the injections: 

Orforglipron (Foundayo) and semaglutide (Wegovy) are both licensed as an adjunct to a reduced-calorie diet and increased physical activity for weight management, including weight loss and weight maintenance, in adults with a BMI of:

• 30 or above, or
• Between 27 and 30, and at least one weight-related comorbidity.