SUN-632 - Efficacy and Safety of the Dual GIP/GLP-1 Receptor Agonist Tirzepatide Versus Selective GLP-1 Receptor Agonists in Adults with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

Background:
Tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, has demonstrated superior metabolic effects in type 2 diabetes mellitus (T2DM). However, its comparative efficacy and safety versus selective GLP-1 receptor agonists (GLP-1RAs) across approved doses remain incompletely defined. We conducted a systematic review and meta-analysis of randomized controlled trials comparing tirzepatide with GLP-1RAs in adults with T2DM.

Methods:
PubMed/MEDLINE, Embase, and the Cochrane Library were systematically searched for randomized controlled trials comparing tirzepatide with GLP-1RAs. Random-effects meta-analyses using inverse-variance methods were performed. Primary outcomes were change in body weight and glycated hemoglobin (HbA1c). Secondary outcomes included attainment of HbA1c ≤6.5% and ≤7.0%, and gastrointestinal adverse events. Results are presented as mean differences (MD) or risk ratios (RR) with 95% confidence intervals (CI). Prespecified subgroup analyses were conducted for tirzepatide 5 mg, 10 mg, and 15 mg. Heterogeneity was assessed using the I² statistic.

Results:
Three randomized comparisons including 2,832 participants (tirzepatide n=2,053; GLP-1RAs n=733) were analyzed. Tirzepatide resulted in greater weight reduction than GLP-1RAs (MD −5.78 kg; 95% CI −7.67 to −3.89; P< 0.00001), with a significant dose–response relationship (P for subgroup differences=0.010). Weight loss increased progressively with dose: 5 mg (MD −3.04 kg), 10 mg (MD −6.02 kg), and 15 mg (MD −8.30 kg).
Tirzepatide achieved superior glycemic control (MD −0.83%; 95% CI −1.16 to −0.49; P< 0.00001). Greater HbA1c reductions were observed with 10 mg (−0.85%) and 15 mg (−1.06%), while the 5 mg dose showed a smaller, borderline effect; no significant differences between dose subgroups were detected (P=0.57). Tirzepatide increased attainment of HbA1c ≤6.5% (RR 1.70; 95% CI 1.34–2.15) and ≤7.0% (RR 1.25; 95% CI 1.13–1.38).
Across 2,727 participants, tirzepatide showed no significant difference in the incidence of vomiting (RR 1.21; P=0.38) or nausea (RR 1.15; P=0.17) compared with GLP-1RAs, while diarrhea occurred more frequently (RR 1.36; P=0.01).

Conclusion:
In adults with T2DM, tirzepatide provides clinically meaningful, dose-dependent weight loss and superior glycemic control compared with selective GLP-1 receptor agonists, with a generally comparable gastrointestinal safety profile.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*