Obesity is a complex chronic disease and a major public health challenge. The emergence of glucagon-like peptide-1 (GLP-1) receptor agonists has significantly changed its treatment landscape. Originally developed for type 2 diabetes, these medicines have demonstrated substantial weight-loss effects and additional health benefits in certain patient populations.
In December 2023, Science named GLP-1-based weight-loss medicines its 2023 Breakthrough of the Year. The recognition reflects their clinical potential, while also highlighting questions about long-term treatment, safety, affordability and access.
From diabetes treatment to obesity medicine
GLP-1 is a naturally occurring gut hormone involved in blood glucose regulation and appetite control. GLP-1 receptor agonists mimic some of its effects, helping regulate blood sugar and reduce appetite.
The first medicine in this class, exenatide (Byetta), was approved in the United States in 2005 for type 2 diabetes. Liraglutide followed, initially for diabetes and later in a higher-dose formulation (Saxenda) for weight management. Semaglutide subsequently became available as Ozempic for type 2 diabetes and Wegovy for chronic weight management. The FDA approved Wegovy in June 2021.
Clinical evidence and benefits beyond weight loss
The STEP 1 clinical trial, published in 2021, demonstrated the weight-loss potential of semaglutide. Adults with obesity or overweight receiving a 2.4 mg weekly dose alongside lifestyle interventions lost an average of 14.9% of their initial body weight after 68 weeks, compared with 2.4% in the placebo group.
Semaglutide reduces appetite and energy intake. Some patients also report fewer persistent thoughts about food, informally described as “food noise”. Individual treatment outcomes nevertheless vary.
Research published in 2023 also provided evidence of benefits beyond weight reduction:
The STEP-HFpEF trial found that semaglutide improved symptoms, physical limitations and exercise function in people with obesity and heart failure with preserved ejection fraction.
The SELECT trial found a 20% relative reduction in major adverse cardiovascular events — cardiovascular death, non-fatal heart attack or non-fatal stroke — among people with overweight or obesity and established cardiovascular disease but without diabetes.
These findings broadened the understanding of the potential health benefits of GLP-1 medicines. However, they relate to specific patient populations and should not be interpreted as evidence of universal cardiovascular protection.
Safety, affordability and long-term treatment
Despite their promising results, GLP-1 receptor agonists have limitations. Common side effects include nausea, vomiting, diarrhoea and constipation. Their frequency and severity vary, and some patients may need to adjust or discontinue treatment.
Long-term use is another important consideration. Weight may return after treatment is stopped, meaning that obesity management may require ongoing medical support rather than a short course of medication.
Affordability and availability also affect access. Treatment can be expensive, particularly where reimbursement is limited, and prices vary between countries and healthcare systems. These factors make cost-effectiveness and equitable access important issues for healthcare providers and policymakers.
Potential applications under investigation
Researchers are also exploring whether GLP-1 medicines could have applications beyond diabetes and obesity. Areas of interest include substance-use disorders and neurodegenerative conditions such as Alzheimer’s and Parkinson’s disease.
As of January 2024, however, these applications remained investigational. Early research does not establish that GLP-1 receptor agonists are effective treatments for these conditions, and further clinical studies are required.
A changing understanding of obesity
The development of GLP-1 medicines is contributing to a broader understanding of obesity as a chronic condition influenced by biological, genetic, environmental and social factors — rather than simply a matter of willpower. By targeting biological mechanisms involved in appetite and metabolism, these medicines offer an additional treatment option and may help reduce the stigma associated with obesity.
Conclusion
GLP-1 receptor agonists represent a significant advance in obesity treatment. Clinical studies have demonstrated substantial weight loss with semaglutide and identified additional cardiovascular benefits in specific patient populations.
Nevertheless, questions remain about long-term safety, treatment duration, affordability and access. Potential applications in other diseases also require further investigation. The long-term impact of these medicines will depend on continued research, responsible prescribing and their integration into comprehensive obesity care.
View source version on Science.
