Across randomized trials in adults with obesity, all studied medications reduced body weight more than placebo, with semaglutide and tirzepatide showing the largest losses.
Evidence
This systematic review and network meta-analysis synthesized 56 randomized clinical trials involving 60,307 adults and found significant weight-loss benefits for all included obesity medications, with more than 10% for semaglutide and tirzepatide.
Caveat
Because this was a network meta-analysis pooling trials with different drugs, comparators, outcomes, and follow-up lengths, it supports comparative trends more than definitive head-to-head conclusions for every endpoint.
Simplified
This systematic review and network meta-analysis evaluated the efficacy and safety of (OMMs) in terms of reducing body weight and impact on obesity-related complications. Here a Medline and Embase search was performed up to 31 January 2025 for randomized controlled trials comparing OMMs versus placebo/active comparators in adults. Primary endpoint was percentage of (TBWL%) at the end of the study. Secondary endpoints were TBWL% at 1, 2 and ≥3 years, lipid profile, blood pressure, hemoglobin A1c, fasting plasma glucose, mental health, serious adverse events, quality of life, cardiovascular morbidity and mortality, remission of obesity-related complications and all-cause mortality. Fifty-six clinical trials were identified-orlistat (22), semaglutide (14), liraglutide (11), tirzepatide (6), naltrexone/bupropion (5) and phentermine/topiramate (2)-enrolling 60,307 patients (32,598 OMM and 27,709 placebo). All OMMs showed a significantly greater TBWL% versus placebo (P < 0.0001), more than 10% for semaglutide and tirzepatide. Both tirzepatide and semaglutide showed normoglycemia restoration, remission of type 2 diabetes and reduction in hospitalization due to heart failure. Semaglutide was effective in reducing major adverse cardiovascular events and reducing pain in knee osteoarthritis. Tirzepatide was effective in remission of obstructive sleep apnea syndrome and metabolic dysfunction-associated steatohepatitis. These results support the need to individualize the selection of OMMs.
Key numbers
10.6%
Weight Loss Improvement
Percentage of (TBWL%) for semaglutide and tirzepatide.
60,307 patients
Patient Enrollment
Total number of patients enrolled across all included trials.
67%
Weight Regain After Discontinuation
Average percentage of weight regained after discontinuation of semaglutide treatment.
Full Text
We can’t show the full text here under this license.
Competing interests: B.M. has received speaker and/or advisory fees from Novo Nordisk, Eli Lilly, AstraZeneca, Janssen, Pfizer and Merck Sharp & Dohme and a research grant from Novo Nordisk. B.M. is a shareholder of Reset Health. A.C. has received speaking fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Sanofi and Menarini and research grants from Eli Lilly, Novo Nordisk and Menarini. A.C. is also a member of the Data Monitoring Committee of Boehringer Ingelheim. J.L.B. has received a consulting fee and is an advisory board member for Novo Nordisk, with fees paid to her institution. L.B. has received payment of honoraria from Eli Lilly, Novo Nordisk, Boehringer Ingelheim, Pfizer, Bruno Farmaceutici, Regeneron, Rythm Pharmaceuticals and Pronokal as speaker and/or member of advisory boards. D.D. has received speaker and advisory board fees from Boehringer Ingelheim, Eli Lilly, Novo Nordisk and AstraZeneca and research grants from Eli Lilly, Novo Nordisk and Boehringer Ingelheim. G.F. has received payment of honoraria from Eli Lilly, Novo Nordisk, Regeneron and AstraZeneca as speaker and/or member of advisory boards and payment of honoraria as member of the OPEN Spain Initiative. G.H.G. has no relevant conflicts of interest to declare related to this article. M.M. has received speaking fees from AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novo Nordisk, Sanofi and Novartis and research grants from Bristol Myers Squibb. P.S. received payment of honoraria and consulting fees from Boehringer Ingelheim, Chiesi, Novo Nordisk, Eli Lilly, Pfizer and Roche as a member of advisory boards. B.M.-T. has received grants from the EASO New Clinical Investigator Award 2024 and the EFSD Rising Star 2024, both supported by the Novo Nordisk Foundation. E.W. has no conflicts of interest to declare. V.Y. was engaged in advisory boards and lectures with Novo Nordisk, Eli Lilly, Rhythm and Regeneron.
GLP-1 Therapies