A network meta-analysis backed weight-loss benefits with several GLP-1 receptor agonists, with less certainty for newer-generation agents.Two GLP-1 drugs were also associated with reduced heart failure risk, while subcutaneous semaglutide stood alone in being tied to a reduced risk of all-cause mortality and myocardial infarction.The evidence was less certain for a reduction in kidney failure or an improvement in quality of life beyond a subjective threshold.
Variable weight-loss and cardiovascular benefits were seen with GLP-1 drugs in a systematic review and network meta-analysis, but effects on quality of life were less clear.
Across 262 randomized studies published through November 2025, moderate- to high-certainty evidence showed weight loss with the following GLP-1 drugs at 1 year versus lifestyle modification alone:Tirzepatide (Zepbound): mean difference -14.9% (95% CI -16.0 to -13.9)Cagrilintide-semaglutide (CagriSema): mean difference -14.8% (95% CI -16.9 to -12.7)Oral semaglutide (Rybelsus): mean difference -10.9% (95% CI -12.7 to -9.1)Orforglipron (Foundayo): mean difference -9.9% (95% CI -12.4 to -7.5)Subcutaneous semaglutide (Wegovy): mean difference -9.8% (95% CI -10.6 to -9.1)
