GLP-1 Receptor Agonists Show Promise for Weight Loss in Overweight and Obese Individuals Without Diabetes

A recent study has shed light on the effectiveness and safety of Glucagon-like Peptide-1 (GLP-1) receptor agonists (RAs) for weight reduction in individuals living with overweight and obesity but without diabetes. The research aimed to evaluate the benefit-harm balance of initiating GLP-1 RAs compared to placebo for weight loss.

Methods: The study utilized benefit-harm balance modelling, synthesizing data from 8 randomized controlled trials (RCTs) involving 8847 participants. The analysis focused on the effects of GLP-1 RAs over 1 and 2 years, applying preference weights to outcomes to assess the balance between benefits and harms.

Findings: The study found that of 1000 persons treated with GLP-1 RAs for 2 years, 375 achieved a 10% weight loss, and 318 achieved a 5% weight loss compared to those treated with placebo. However, the GLP-1 RA group experienced more frequent harm outcomes, including abdominal pain, cholelithiasis, constipation, diarrhoea, alopecia, hypoglycaemia, injection site reactions, and vomiting. Achieving a 10% weight loss with GLP-1 RA therapy outweighed the cumulative harms, with a net benefit probability of 0.97 at year 1 and 0.91 at year 2. In contrast, a 5% weight loss did not show a net benefit, with probabilities of 0.13 and 0.01 at year 1 and year 2, respectively.

Interpretation: The study concludes that while GLP-1 RAs can offer significant weight loss benefits, especially for those aiming for a 10% reduction in body weight, the net benefit is highly dependent on individual treatment goals and tolerance for potential harms. This highlights the importance of personalized treatment decisions to optimize benefits and reduce harms. The study also emphasizes the need for continuous monitoring and updating of the benefit-harm balance of GLP-1 RAs due to varying evidence across studies.