What is the efficacy of Semaglutide (Glucagon-like peptide-1 receptor agonist) for weight loss?

From the Guidelines

Semaglutide is a highly effective medication for weight loss in adults with obesity or overweight with weight-related health conditions, with a recommended dose of 2.4 mg injected subcutaneously once weekly. The medication works by mimicking GLP-1, a hormone that regulates appetite and food intake by acting on brain centers that control hunger and satiety, while also slowing stomach emptying 1. According to the most recent and highest quality study, the STEP trials, semaglutide has been shown to result in a mean weight loss of 14.9% and 16.0% at 68 weeks, compared to 2.4% and 5.7% with placebo, respectively 1.

Key Points to Consider

• The medication should be used alongside lifestyle modifications, including diet and exercise, for optimal results 1.
• Common side effects include nausea, vomiting, diarrhea, and constipation, which often improve over time 1.
• Semaglutide is not recommended during pregnancy, for people with certain endocrine tumors, or those with a personal or family history of medullary thyroid cancer 1.
• Insurance coverage varies significantly, and without coverage, the medication can be expensive at approximately $1,300-$1,500 per month 1.
• The AGA suggests using semaglutide 2.4 mg with lifestyle interventions, compared with lifestyle interventions alone, for adults with obesity or overweight with weight-related complications 1.

Benefits and Risks

• Semaglutide has been shown to decrease the risk of CVD events in adults with overweight or obesity without diabetes 1.
• The medication has been associated with lower rates of gastrointestinal adverse events compared to other GLP-1 receptor agonists 1.
• However, there is uncertainty and substantial variability in individuals’ values and preferences between desirable and undesirable effects, and some patients may prefer other available nonpharmacologic therapies for the treatment of obesity 1.

From the FDA Drug Label

Semaglutide lowers fasting and postprandial blood glucose and reduces body weight. All pharmacodynamic evaluations were performed after 12 weeks of treatment (including dose escalation) at steady state with semaglutide 1 mg.

Semaglutide is used for weight loss as it reduces body weight.

• The exact mechanism of weight loss is not explicitly stated, but it is related to its effects on glucose-dependent insulin secretion and glucagon secretion.
• The drug label does mention that semaglutide lowers body weight, but it does not provide specific details on the amount of weight loss or the conditions under which it is most effective for weight loss 2.

From the Research

Efficacy of Semaglutide for Weight Loss

• Semaglutide has been shown to be effective in achieving significant and sustained weight loss in adults with overweight or obesity, with mean weight losses of 14.9%-17.4% from baseline to week 68 3, 4.
• In the STEP 1-5 trials, 69%-79% of participants achieved ≥10% weight loss with semaglutide 2.4 mg, and 51%-64% achieved ≥15% weight loss, compared to 12%-27% and 5%-13% with placebo, respectively 4.
• Semaglutide 2.4 mg once weekly plus lifestyle intervention was associated with a sustained, clinically relevant reduction in body weight, with a mean change in body weight from baseline to week 68 of -14.9% compared to -2.4% with placebo 5.

Safety Profile of Semaglutide

• The safety profile of semaglutide 2.4 mg was consistent across trials, with the most common adverse events being gastrointestinal events, such as nausea and diarrhea, which were typically transient and mild-to-moderate in severity 3, 4, 5.
• More participants in the semaglutide group than in the placebo group discontinued treatment due to gastrointestinal events, but the overall discontinuation rate was low 5.

Cardiometabolic Benefits of Semaglutide

• Semaglutide has been shown to improve cardiometabolic risk factors, including high blood pressure, atherogenic lipids, and physical function, in addition to its weight-loss effects 3, 4, 5.
• The improvements in cardiometabolic risk factors and physical function were seen in both participants with and without type 2 diabetes 4, 5.

Approval and Availability of Semaglutide

• Semaglutide 2.4 mg was approved by the US Food and Drug Administration for chronic weight management in adults with overweight or obesity in April 2021 3, 6.
• Semaglutide is available under the brand name Wegovy for weight loss, and has been shown to be effective in reducing body weight and improving cardiometabolic risk factors 6.