Comparative efficacy and safety of semaglutide 2.4 mg and tirzepatide 5–15 mg in obesity with or without type 2 diabetes: A systematic review of Phase 3 clinical trials
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Abstract
Background and aims
Both semaglutide 2.4 mg and tirzepatide have been recently approved for chronic use in obesity. There is a lack of literature comparing the efficacy and safety of both these agents in people with obesity/overweight with or without type 2 diabetes (T2D). We systematically reviewed Phase 3 randomized controlled trials (RCTs) conducted with two agents to synthesize the comparative efficacy and safety outcomes.
Methods
We systematically searched PubMed electronic databases until December 15, 2024, using selected keywords and Boolean “AND.” Subsequently, we compared the most closely matched trials conducted with semaglutide 2.4 mg and tirzepatide through an adjusted (if baseline imbalance in treatment outcome modifiers present) or unadjusted (in the absence of baseline imbalance) indirect treatment comparison method.
Results
We identified one trial each of semaglutide 2.4 mg (STEP-1) and tirzepatide 5, 10, and 15 mg (SURMOUNT-1) in obese or overweight people without T2D and one trial each of semaglutide 2.4 mg (STEP-2) and tirzepatide 10 and 15 mg (SURMOUNT-2) in overweight people with T2D that were almost entirely comparable concerning baseline outcome modifier characteristics. Our unadjusted analysis without individual patients' data found relatively higher (4 and 5.4 % additional) weight loss, HbA1c (−0.4 % additional) reduction, and fewer gastrointestinal side effects (GI S/E) with tirzepatide 10 and 15 mg, respectively, than with semaglutide 2.4 mg, in the intention-to-treat analysis.
Conclusion
Tirzepatide 10 and 15 mg are more effective and have fewer GI S/E than semaglutide 2.4 mg. A well-powered head-to-head RCT is currently needed to confirm these findings.
期刊介绍:
Diabetes and Metabolic Syndrome: Clinical Research and Reviews is the official journal of DiabetesIndia. It aims to provide a global platform for healthcare professionals, diabetes educators, and other stakeholders to submit their research on diabetes care.
Types of Publications:
Diabetes and Metabolic Syndrome: Clinical Research and Reviews publishes peer-reviewed original articles, reviews, short communications, case reports, letters to the Editor, and expert comments. Reviews and mini-reviews are particularly welcomed for areas within endocrinology undergoing rapid changes.