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Key facts
- GLP-1 drugs have revolutionised the weight loss treatment landscape
- By improving cardiometabolic health, they can also reduce risks associated with cardiovascular disease
- Many chronic diseases are worsened by being overweight or obese, so GLP-1s may have a therapeutic role in many chronic conditions.
Learning objectives
After reading this feature, you should:
- Understand why GLP-1s are used in weight loss and type 2 diabetes management
- Know which other disease areas they could potentially benefit
- Be familiar with the potential safety concerns associated with these drugs.
The introduction of glucagon-like peptide-1 receptor agonists (GLP-1s) has revolutionised weight management services globally. The weight loss they induce improves cardiometabolic health and reduces the risk of cardiovascular disease. However, it is increasingly clear that this relatively new class of drugs has even wider therapeutic potential.
Early work
As early as 1906, researchers found that an intestinal extract could lower blood glucose. This extract was later named ‘incretine’, but interest waned following the discovery of insulin in 1920. During the 1960s, however, there was renewed interest following the observation that when administered orally, glucose increased circulating insulin levels and lowered blood glucose to a greater extent than intravenously administered glucose. This led researchers to speculate that the intestine produced a hormone that regulated insulin levels. However, it was not until 1986 that scientists identified GLP-1 in the intestine, a cleavage product of glucagon, a hormone secreted by pancreatic α cells in response to low blood glucose levels.
Subsequent work confirmed that intestinal glucagon-like peptides were also released in response to glucose. This suggested a potential route for controlling glucose levels in patients with type 2 diabetes and, by the early 1990s, studies confirmed that the intravenous infusion of GLP-1 significantly increased insulin levels and lowered blood glucose. Another curious finding from 1999 rodent studies was that GLP-1 was a potent inhibitor of feeding and appeared to play a physiological role in regulating bodyweight.
The GLP-1 molecule itself was unstable, necessitating considerable effort to develop structurally similar molecules suitable for clinical use. In 2005, the first GLP-1 drug – exenatide – received FDA approval in the US for the treatment of patients with type 2 diabetes. Today, several GLP-1 drugs are available, which work by binding to GLP-1 receptors in the intestine. But the earlier observed potential for weight loss had not gone unnoticed.
In 2014, liraglutide became the first GLP-1 approved for weight loss. Later studies with another GLP-1 (semaglutide) showed that the drug induced average weight losses of around 15 per cent, significantly higher than placebo.
Another drug that has gained popularity is tirzepatide. The drug has a dual mode of action, targeting both the GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors.
GLP-1 impact on weight loss
A slew of large-scale studies has confirmed that GLP-1 drugs can induce significant weight loss. It has also been demonstrated that when used in non-diabetic patients with pre-existing cardiovascular disease and overweight or obesity, these drugs significantly reduce the incidence of death from cardiovascular causes, nonfatal myocardial infarction, and nonfatal stroke.
Despite this, a 2024 meta-analysis that included 13 randomised controlled trials with 30,512 patients living with overweight or obesity was more circumspect.
Whilst the role of GLP-1 agents and tirzepatide in weight management is now well established, researchers have turned their attention to whether these drugs might benefit other health conditions associated with systemic inflammation. Some areas of active research that have demonstrated promise for GLP-1 drugs are discussed below.
Is there a role for GLP-1s in treating neurological disorders?
As early as 1999, researchers linked type 2 diabetes with cognitive impairment. Indeed, there appears to be a relationship between type 2 diabetes and Alzheimer’s disease, with some scientists referring to Alzheimer’s as type 3 diabetes.
Although this is still an area of active debate, evidence suggests that brain insulin resistance (also present in type 2 diabetes) dysregulates signalling and is observed in patients with Alzheimer’s disease. Based on this association, a phase 2 trial in patients with mild-to-moderate Alzheimer’s given liraglutide demonstrated a beneficial effect by slowing cognitive deterioration.
Further work summarising data on the other GLP-1 drugs has revealed how these agents exhibit neuroprotective mechanisms via anti-inflammatory actions, thereby enhancing synaptic function and reducing amyloid plaque formation.
GLP-1s might also be of value to patients with Parkinson’s disease, based on observations from mouse models. In 2024, a trial explored the use of the GLP-1 lixisenatide to slow motor disability progression in Parkinson’s disease. The study found that lixisenatide resulted in less progression of motor disability than placebo at 12 months.
GLP-1 receptors are found in several regions of the brain, and some preclinical studies have described the role of GLP-1 in reward processing, stress regulation and cognitive function.
The fact that GLP-1s affect reward pathways in the brain, reducing the pleasure and motivation associated with high-calorie foods suggests a potential role in treating substance misuse disorder. What’s more, such drugs could be useful.
For example, in one phase II trial of patients with alcohol use disorder, low dose semaglutide (0.25 mg/week) for four weeks reduced the amount of alcohol consumed during a post-treatment laboratory self-administration task compared with placebo.
However, while there might be a role for GLP-1 drugs in the management of those with substance misuse disorders, the benefits are probably only relevant for those with metabolic dysfunctions such as type 2 diabetes and obesity.
Evidence points to a potential positive effect on knee osteoarthritis
Patients with osteoarthritis (OA) can experience pain in weight-bearing joints such as the knee. Since weight loss is associated with improvements in osteoarthritic pain, researchers explored whether semaglutide could help patients with osteoarthritis.
In the STEP9 trial, overweight and obese patients with OA given semaglutide observed a significant reduction in knee pain, together with less use of analgesics. Whether the reduction in pain was simply mediated by weight loss or by another mechanism remains unclear, though in vitro studies have shown that liraglutide, for instance, inhibits the secretion of pro-inflammatory mediators and induces cartilage protective effects.
Obesity is a recognised and modifiable risk factor for obstructive sleep apnoea (OSA), so GLP-1s could prove beneficial. The value of tirzepatide in moderate-to-severe OSA was examined in the SURMOUNT-OSA trial, which enrolled patients with a body mass index of 38 to 39. After 52 weeks of treatment, there was a significant reduction in the apnoea-hypopnea index (which quantifies the severity of OSA) and in body weight.
In fact, based on the trial's findings, the FDA approved tirzepatide in the US for moderate-to-severe OSA in adults with obesity when used in combination with a reduced-calorie diet and increased physical activity.
Reduced risk of asthma exacerbation
The identification of GLP-1 receptors in lung epithelial and endothelial cells suggests a possible role in pulmonary diseases. Animal studies have already shown that GLP-1 drugs significantly inhibit allergic and viral airway inflammation, reducing airway eosinophilia, mucus production and hyperresponsiveness.
Two retrospective studies suggest that the drugs have a role in asthma. In the first, patients with both type 2 diabetes and asthma who were prescribed a GLP-1 found their asthma exacerbation levels decreased. In the second, among adolescents with overweight and obesity prescribed GLP-1 drugs, a lower risk of acute asthma exacerbations was observed.
Although both studies were retrospective (an important limitation) they do serve as a basis for more robust studies to examine whether GLP-1 drugs reduce the risk of asthma exacerbations.
Positive findings for testicular dysfunction
Male infertility and hypogonadism are common among men with metabolic syndrome. In addition, animal and human studies have identified GLP-1 receptors on Leydig and Sertoli cells, which reside in the testes and are involved in sperm production, as well as on spermatozoa themselves.
In a recent analysis of seven studies involving 680 men with overweight and obesity, researchers found that treatment with GLP-1 drugs significantly increased total serum testosterone, serum gonadotropins and indices of erectile function.
Other work suggests that GLP-1s can improve libido and the severity of erectile dysfunction. Taken together, these preliminary findings would suggest that GLP-1s may influence male reproductive hormones through mechanisms involving weight loss and improved insulin sensitivity.
Polycystic ovary syndrome improvements
Women with polycystic ovary syndrome (PCOS) experience insulin resistance, hyperandrogenism, ovulatory dysfunction and obesity. In other words, PCOS is characterised to some extent by metabolic impairment.
The evidence to date indicates that in women with PCOS, the drugs improved natural pregnancy rates, induced a more regular menstrual frequency and led to improvements in obesity, insulin resistance and gonadal parameters.
Remaining questions
There is no doubt that GLP-1s have the potential to become an important therapeutic option for several diseases. However, several questions remain, including their long-term efficacy and safety. Additionally, given the current costs of these agents, there is a need to identify relevant genetic or biomarkers to determine which patients are most likely to respond.
Furthermore, research is needed to better understand the cost-benefit analysis of these drugs and the possible financial impact on healthcare systems until generic versions become more widely available.
The GLP-1 drugs may have revolutionised the weight-loss market, but it seems that these agents are set to play a much wider therapeutic role in the future.
Potential safety concerns
While there is a good deal of preliminary data suggesting that GLP-1s have therapeutic potential beyond weight loss, this must be balanced against the risk of adverse effects. Two of the most prominent safety concerns relate to cancer and optic neuropathy.
Cancer risk
The development of adverse gastrointestinal effects, such as nausea, is accepted, but emerging data from 2011 also highlight the risk of acute pancreatitis and even pancreatic cancer. Fortunately, one nine-year follow-up study, which included over 500,000 adults prescribed GLP-1 drugs, found no evidence of an increase in pancreatic cancer.
Moreover, a review of GLP-1 medicines and cancer in November 2025 found that GLP-1 agonists reduced cancer risk in many people with type 2 diabetes or obesity.
Currently, none of the GLP-1 drugs has pancreatic cancer listed as an adverse effect, although the MHRA has launched a study into whether an individual’s genes may increase their risk of developing acute pancreatitis when taking GLP-1s for weight loss and type 2 diabetes.
Since obesity is a recognised risk factor for many types of cancer, an important question is whether GLP-1 drugs might actually reduce the cancer risk in those with obesity. One recent retrospective analysis published in JAMA Oncology provided some much-needed reassurance.
The study looked at 86,632 adults (43,317 who were prescribed a GLP-1 drug) who were matched with GLP-1 users, and the researchers looked at 14 different types of cancer. Overall, there was a 17 per cent lower risk of developing cancer in those prescribed a GLP-1 drug, but a slightly and non-significantly higher risk of kidney cancer.
Non-arteritic anterior ischaemic optic neuropathy
Some data point to an increased risk of non-arteritic anterior ischaemic optic neuropathy (NAAION) in those using GLP-1s. NAAION is one of the most common causes of acute optic nerve–related vision loss in people over 50 years of age. It is characterised by sudden, painless unilateral vision loss due to optic nerve ischaemia. In fact, there have been several studies as well as case reports of an association between GLP-1 drug use and NAAION.
For example, a recent Danish cohort study with over 60,000 individuals with type 2 diabetes found an almost threefold higher risk of NAAION among those using semaglutide compared with SGLT-2 inhibitors.
In contrast, some observational studies have failed to detect such an association. While the risk of NAAION with GLP-1 agents is uncommon, greater exposure to these drugs may lead to a higher number of cases being reported.
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