The efficacy and safety of dual GIP/GLP1 receptor agonists (tirzepatide) in diabetes and obesity: a systematic review and network meta-analysis.

BACKGROUND: Tirzepatide has shown benefits in weight reduction and glycemic control in type 2 diabetes and obesity, but its relative efficacy and safety across doses remain unclear. METHODS: We conducted a PROSPERO-registered systematic review and network meta-analysis of randomized controlled trials up to July 2024. Trials comparing tirzepatide (5, 10, or 15 mg weekly) with placebo, insulin, or GLP-1 receptor agonists in adults with type 2 diabetes and/or obesity were included. Random-effects models estimated mean differences (MDs) or relative risks (RRs), with treatment ranking assessed by SUCRA and evidence certainty rated with CINeMA. RESULTS: Thirteen RCTs (14,007 participants) were included. Tirzepatide produced dose-dependent weight reductions versus insulin (MD -14.5 kg for 15 mg; -12.5 kg for 10 mg; -10.2 kg for 5 mg; all < 0.0001). The likelihood of ≥15% weight loss (RR 4.83 for 15 mg), HbA1c reduction (MD -12.6 mmol/mol), and normoglycemia (RR 11.3) was significantly higher with tirzepatide. Safety analyses showed fewer serious adverse events (RR 0.71-0.77) and hypoglycemia (RR 0.44-0.50) than insulin, but more gastrointestinal events. CONCLUSIONS: Tirzepatide provides superior weight loss, glycemic improvements, and favorable safety versus insulin and other comparators, supporting its role as a leading therapy for type 2 diabetes and obesity.