SURPASS Clinical Trial Program: Complete Overview of All Diabetes Studies
A comprehensive review of the SURPASS-1 through SURPASS-5 clinical trials that established tirzepatide as a leading treatment for type 2 diabetes.
The SURPASS clinical trial program was the pivotal series of Phase 3 studies that led to the FDA approval of Mounjaro (tirzepatide) for type 2 diabetes. Here's a comprehensive review of each study.
SURPASS-1: Tirzepatide as Monotherapy
Design: 478 patients with T2D inadequately controlled with diet and exercise alone; 40 weeks.
Results:
- HbA1c reductions: -1.87% (5 mg), -1.89% (10 mg), -2.07% (15 mg) vs. +0.04% (placebo)
- Weight loss: -7.0 kg (5 mg), -7.8 kg (10 mg), -9.5 kg (15 mg) vs. -0.7 kg (placebo)
- Up to 52% of patients achieved HbA1c <5.7% (normoglycemia)
SURPASS-2: Tirzepatide vs. Semaglutide
Design: 1,879 patients on metformin; tirzepatide vs. semaglutide 1 mg; 40 weeks.
Results:
- All tirzepatide doses were superior to semaglutide for HbA1c reduction
- Weight loss was significantly greater with tirzepatide 10 mg and 15 mg
- This was the first head-to-head trial showing superiority over semaglutide
SURPASS-3: Tirzepatide vs. Insulin Degludec
Design: 1,444 patients on metformin ± SGLT2 inhibitor; tirzepatide vs. insulin degludec; 52 weeks.
Results:
- HbA1c: -1.93% to -2.37% (tirzepatide) vs. -1.34% (insulin degludec)
- Weight: tirzepatide produced weight loss of 7.5-12.9 kg while insulin degludec caused weight gain of +2.3 kg
- Demonstrated tirzepatide could replace insulin with better outcomes
SURPASS-4: Tirzepatide vs. Insulin Glargine
Design: 2,002 patients with T2D and increased cardiovascular risk; up to 104 weeks.
Results:
- Superior HbA1c reduction with all tirzepatide doses vs. insulin glargine
- Significant weight loss vs. weight gain with insulin
- Favorable cardiovascular safety profile
- Demonstrated long-term safety and efficacy
SURPASS-5: Tirzepatide as Add-on to Insulin Glargine
Design: 475 patients already on insulin glargine ± metformin; 40 weeks.
Results:
- Additional HbA1c reductions of -2.11% to -2.59% when added to basal insulin
- Weight loss of -5.4 kg to -10.5 kg despite being on insulin
- Demonstrated compatibility with insulin therapy
Overall Conclusions from SURPASS
Across all five trials, tirzepatide consistently demonstrated:
- Superior glycemic control compared to placebo, semaglutide, and insulin
- Clinically meaningful weight loss across all populations
- Acceptable safety profile with primarily gastrointestinal side effects
- Potential to replace or augment insulin therapy
- Benefits in patients across the spectrum of T2D severity