Efficacy and Safety of Once-Weekly Semaglutide versus Tirzepatide in Type 2 Diabetes: A 24-Week Randomized Clinical Trial

Abstract

Background: Type 2 diabetes mellitus commonly coexists with obesity, and many patients require treatment that improves both glycaemic control and body weight. Objective: To compare the 24-week efficacy and tolerability of once-weekly semaglutide and tirzepatide in adults with type 2 diabetes mellitus and obesity receiving stable metformin and empagliflozin therapy. Methods: This single-centre, open-label, parallel-group randomized clinical trial included 79 participants at The Doctors Hospital, Lahore, Pakistan. Participants were allocated to semaglutide (n=38), administered at 0.25 mg weekly for four weeks and 0.5 mg weekly thereafter, or tirzepatide (n=41), administered at 2.5 mg weekly for four weeks and 5 mg weekly thereafter. Both groups continued metformin 2 g/day and empagliflozin 25 mg/day and followed a low-calorie diet. Primary outcomes were changes in body mass index and HbA1c at 24 weeks. Results: Baseline BMI was 33.8 kg/m² in the semaglutide group and 34.2 kg/m² in the tirzepatide group, while baseline HbA1c was 7.7% and 7.9%, respectively. Mean BMI reduction was greater with tirzepatide than semaglutide (5.9 versus 3.1 kg/m²; p<0.001). Mean HbA1c reduction was also greater with tirzepatide (1.4 versus 0.9 percentage points; p=0.0005). Treatment discontinuation attributed to intolerance occurred in three semaglutide-treated and two tirzepatide-treated participants. Mild hypoglycaemia occurred in one and two participants, respectively. Conclusion: Tirzepatide 5 mg produced greater reported reductions in BMI and HbA1c than semaglutide 0.5 mg over 24 weeks. Safety findings were limited by the small sample and low event frequency