Efficacy and Safety of Glucagon-Like Peptide-1 Receptor Agonists for Obesity Management in Adults With and Without Type 2 Diabetes: A Systematic Review.
Velji-Ibrahim. Jena J; Radadiya. Dhruvil D; Devani. Kalpit K; Patel. Harsh H; Nathani. Piyush P; Hassan. Cesare C; Pugliese. Nicola N; Thompson. Christopher C; Sharma. Prateek P
Key Findings
- Tirzepatide 15â¯mg caused about a 9.5â¯kg loss (â20% of body weight) in diabetics over 40â¯weeks and up to 20.9% loss over 72â¯weeks in nonâdiabetics
- Semaglutide 2.4â¯mg gave similar weight loss (â9.6% in diabetics, 14.9% in nonâdiabetics)
- All GLPâ1 receptor agonists, including tirzepatide, raised rates of nausea, vomiting and diarrhea but did not increase serious adverse events compared with placebo
Practical Outcomes
- If youâre looking for a powerful weightâloss peptide, tirzepatide at 15â¯mg is a top candidate, but start low and increase slowly to manage GI side effects. Pair the drug with a lowâcalorie diet and monitor weight and tolerance regularly. Consider cost and availability, as cheaper options like liraglutide are less effective but may be more accessible.
Summary
Big studies show that the drug tirzepatide, especially at the 15â¯mg dose, can cut body weight by around 10â¯kg in people with diabetes and up to 21% in those without diabetes, making it one of the strongest weightâloss tools we know of. It works about as well as the highâdose version of semaglutide, but both cause more stomach upset than a placebo, while serious risks like pancreatitis stay low.
Abstract
This systematic review aimed to assess the efficacy and safety of GLP-1 RAs in adults with obesity or overweight, by comparing different GLP-1 RAs, identifying the most effective agents, and evaluating adverse effects. We systematically searched Embase, MEDLINE, and Cochrane for phase 3 and 4 randomized controlled trials (RCTs) with a minimum duration of 40 weeks. Included studies compared GLP-1 RAs to placebo or to each other in adults with obesity (BMI ≥ 30 kg/m<sup>2</sup>) or overweight (BMI ≥ 27 kg/m<sup>2</sup>), with or without type 2 diabetes (T2DM). We excluded crossover trials, open-label studies, early-phase trials, and studies focusing on specific subpopulations. A total of 22 RCTs involving 41,757 participants were included. Among adults with T2DM, the greatest weight reductions were observed with tirzepatide 15 mg (-9.5 kg at 40 weeks; 72% lost ≥ 5% of baseline weight) and semaglutide 2.4 mg (-9.6% body weight at 68 weeks; 69% lost ≥ 5%). In participants without T2DM, semaglutide 2.4 mg (-14.9% body weight at 68 weeks) and tirzepatide 15 mg (-20.9% at 72 weeks) produced the most substantial effects, while semaglutide 50 mg was also effective in nondiabetic patients. Liraglutide 3 mg showed modest efficacy. Across trials, GLP-1 RAs were consistently associated with a higher frequency of gastrointestinal adverse events compared to placebo, including nausea (14%-28% vs. 5%-10%), vomiting (6%-12% vs. 2%-4%), and diarrhea (8%-20% vs. 4%-7%). The risk of pancreatitis and serious adverse events remained comparable to placebo. GLP-1 RAs, especially semaglutide and tirzepatide, are effective for weight management. Liraglutide may remain a viable, cost-effective alternative.
Study Information
pubmed
2025
2025-10-19T00:00:00.000Z
10.1155/jobe/3897161
52