Aims: This meta‐analysis evaluates the rates of pancreatitis/pancreatic cancer among glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) in randomised controlled trials (RCTs). Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA), a systematic search was performed in PubMed, Embase, and Cochrane Library for GLP‐1 RA RCTs that evaluated pancreatitis/pancreatic cancer. A meta‐analysis was conducted to evaluate this risk; subgroup analysis was performed with and without background medications. Results: 62 studies utilising dulaglutide, exenatide, liraglutide, semaglutide, beinaglutide, retatrutide, or tirzepatide, with 66,232 patients, mean age of 58.3 years (14.4 to 68), and mean follow‐up of 43.5 weeks (1 to 198) were included in this study. Meta‐analysis showed a significantly increased risk of pancreatitis (RR: 1.44, 95% CI 1.09–1.89, p = 0.009), but not when stratified by background medications (RR: 1.28, 95% CI 0.87–1.87) and without background medications (RR: 1.37, 95% CI 0.91–2.05). Pancreatic cancer and GLP‐1 RA use showed no significant association (RR: 1.30, 95% CI 0.86–1.97). However, a significant increase was found with background medications (RR: 1.85, 95% CI 1.05–3.26, p = 0.03), but not without (RR: 0.81, 95% CI 0.43–1.55). Conclusion: GLP‐1 RAs carry a slightly increased risk of pancreatitis, which is not significant when stratified by background medication use. Overall risk for pancreatic cancer was not observed, but a slight association was found when stratified with background medications. However, this difference is likely minimal, given the numerous studies excluded from the meta‐analysis where both treatment arms had zero events.

Introduction: Glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) have emerged as an efficacious treatment for type 2 diabetes mellitus (T2DM) and have demonstrated substantial weight loss effects. This systematic review compares two prevalent GLP‐1RAs, tirzepatide and semaglutide, with their weight loss effects and rates of adverse events (AEs).Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA), a systematic search was performed in PubMed, Embase and Cochrane Library for direct comparative studies between tirzepatide and semaglutide. A meta‐analysis was conducted via a random‐effects model to analyse the differences in weight loss outcomes between study cohorts.Results: Four studies, with 28,827 patients (14,870 tirzepatide/13,928 semaglutide), mean age of 55.7 years (52.0 to 63.7) and mean follow‐up of 35.9 weeks (23.6 to 44.6), were included in this study. Mean weight change across four studies for tirzepatide and semaglutide was −11.4% (−15.3% to −8.27%) and −7.3% (−8.3% to −6.08%), respectively. The meta‐analysis supports these findings with a mean difference of −4.84 kg (95% CI: −6.21 to −3.47), favouring tirzepatide. The most common AEs were minor and moderate‐severity gastrointestinal (GI) AEs.Conclusion: Current literature supports tirzepatide demonstrating a higher impact on weight loss than semaglutide, with both demonstrating high rates of minimal‐ to moderate‐severity AEs. Further research with comparative head‐to‐head trials will better elucidate these weight loss effects and safety profiles.

Glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) have demonstrated substantial weight loss effects among patients with diabetes and obesity. However, given the rapid weight loss induced, there is concern about the total change in body composition, including lean body mass (LBM). Current literature on these effects contains significant heterogeneity, with some studies reporting a loss of 40%–60% of LBM and others reporting 15% or less. To combat this, selective androgen receptor modulators (SARMs) have become a popular candidate. Given their androgen receptor selectivity, SARMs have notable anabolic properties and proposed improved safety profiles over traditional anabolic compounds. Several of these agents, such as enobosarm, have been investigated in clinical trials involving older patient populations or patients with cachexia or sarcopenia secondary to chronic diseases. Furthermore, other agents to maintain or enhance LBM, such as antimyostatin agents, are also under investigation. Exploring this potential synergy could lead to better weight loss and body composition management in patients using GLP‐1 RAs for diabetes or weight loss therapy. This review aims to evaluate the potential benefits and uses of SARMs in ameliorating the body composition changes induced by GLP‐1 RAs. Other investigational agents to retain or increase muscle mass and the future possibilities of these drugs will be discussed.