tirzepatide mastery course
Unit 6 of 12

Clinical Evidence: Diabetes

the SURPASS program -- five phase 3 trials that established tirzepatide as the most effective incretin therapy

The Trial Program That Changed the Standard

The SURPASS clinical program comprised five pivotal phase 3 trials enrolling over 6,000 adults with type 2 diabetes. Across every comparator -- placebo, semaglutide 1mg, insulin degludec, and insulin glargine -- tirzepatide demonstrated superior HbA1c reductions and weight loss. SURPASS-2, the head-to-head trial against semaglutide, was the landmark: tirzepatide at all three doses outperformed the leading GLP-1 agonist on both primary and key secondary endpoints. This unit walks through the evidence trial by trial.

SURPASS Trial Comparison

Compare outcomes across all five SURPASS trials and see how tirzepatide performed against each comparator.

interactive SURPASS trial comparison
5
major phase 3 trials in the surpass program, all showing superiority over comparators
-2.30%
hba1c reduction with tirzepatide 15 mg vs -1.86% with semaglutide 1 mg in surpass-2
87-97%
of participants achieved hba1c below 7% (ada target) across all surpass trials
-12.9 kg
best weight reduction across surpass trials (surpass-3 vs insulin degludec)
SURPASS-2 used semaglutide 1 mg, not 2.4 mg. The head-to-head comparison was against the T2D dose (Ozempic), not the higher obesity dose (Wegovy). An adjusted indirect treatment comparison suggested tirzepatide 10 mg and 15 mg would still be superior to semaglutide 2 mg, but this is not the same as a direct trial at matched maximum doses.

key terms for this unit

S surpass clinical program
The phase 3 clinical trial program comprising five major trials that evaluated tirzepatide across the full spectrum of type 2 diabetes treatment, from monotherapy to add-on to insulin.
H hba1c biomarker
Glycated hemoglobin, a measure of average blood glucose over the preceding 2-3 months. The ADA target is below 7%, and the non-diabetic threshold is below 5.7%.
N noninferiority trial design
A statistical test showing that a new treatment is not meaningfully worse than a comparator. In SURPASS-2, all three tirzepatide doses met noninferiority and then demonstrated superiority to semaglutide 1 mg.
O open-label trial design
A trial design where both patients and investigators know which treatment is being administered. SURPASS-2 was open-label, which can introduce potential bias in subjective endpoints.
I insulin degludec comparator drug
An ultra-long-acting basal insulin used as the comparator in SURPASS-3. Patients on degludec gained +2.3 kg while those on tirzepatide lost up to -12.9 kg.