Abstract:
Introduction: GLP-1 medications are taking the market by a storm. Despite their popularity, concerns remain about the short and long-term safety of GLP-1 medications in different patient populations. Here, we compare the safety and efficacy of GLP-1 medications to non-GLP-1 medications for obesity and to GLP-1 medications for Type II Diabetes.
Methods: We reviewed US FDA Medical and Statistical reports (https://www.accessdata.fda.gov/), focusing on approved GLP-1 weight loss (WM) drugs liraglutide, semaglutide, tirzepatide, and non-GLP- 1 agents orlistat, phentermine/topiramate. We also reviewed GLP-1 type 2 diabetes (T2D) drugs semaglutide, tirzepatide, exenatide, lixisenatide, albiglutide. We collected data on patient numbers, body weight, HbA1c, serious adverse events (SAEs), and mortality. Patient exposure years (PEY) were obtained or calculated from trial data.
Results: Across 29,245 patients in WM and T2D trials, the overall mortality rate was 0.3%. In GLP-1 WM trials, mortality was 0.2% in both the drug and placebo groups. Non-GLP-1 WM trials reported mortality rates of 0.2% with the drug and 0.3% with placebo. In T2D trials, mortality was 0.4% with GLP-1 drugs and 0.5% with placebo. Using the PEY method, mortality rate for GLP-1 WM trials per 100K PEY is 124.6 for the drug group and 286.8 for the placebo group. For non-GLP-1 WM trials the mortality rate per 100K PEY is 223.3 for the drug group and 355 for the placebo group. Similarly, for T2D trials the mortality rate per 100K PEY is 398.5 for the drug group and 583.8 for the placebo group. Body weight changes showed similar trends. In GLP-1 WM trials, patients lost an average of 11.1% of body weight with treatment, compared to 1.7% with placebo. Non-GLP-1 WM trials showed a 9.8% weight loss with the drug and 1.9% with placebo. In T2D GLP-1 trials, weight loss was 4.2% with treatment and 0.5% with placebo.
Conclusion: This review of FDA medical and statistical reports suggests that GLP-1 agents, when compared to non-GLP-1 medications for weight management and to placebo in both weight loss and Type 2 diabetes trials, are associated with comparable or lower mortality rates and greater weight reduction. Mortality per patient-exposure year was consistently lower in treatment groups receiving GLP-1 agents. Weight loss outcomes were also more pronounced with GLP-1 therapies across indications. While these findings highlight potential advantages, ongoing monitoring and further research are needed to assess long-term safety and efficacy.
