Results from the SURPASS-2 clinical trial evaluating the effects of tirzepatide in patients with type 2 diabetes showed that the investigational treatment led to superior hemoglobin A1c (HbA1c) and body weight reductions when compared with injectable semaglutide. 

The 40-week SURPASS-2 trial ( NCT03987919) is part of a phase 3 global clinical development program for tirzepatide, a novel, once-weekly, dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist that integrates the actions of both incretins into a single molecule. The multicenter, randomized, parallel, open-label study compared the safety and efficacy of tirzepatide to semaglutide in adults with type 2 diabetes inadequately controlled with at least 1500mg/day of metformin alone (N=1879; mean duration of diabetes, 8.6 years).

Patients were randomly assigned 1:1:1:1 to either tirzepatide 5mg, 10mg or 15mg or semaglutide 1mg. The primary end point of the study was the change from baseline to week 40 in HbA1c. The study was meant to demonstrate that the 2 higher doses of tirzepatide (10mg and 15mg) were noninferior to semaglutide.

Efficacy estimand results (which represents efficacy prior to discontinuation of study drug or initiating rescue therapy for persistent severe hyperglycemia), for tirzepatide 5mg, 10mg, and 15mg vs semaglutide, respectively, included the following:

  • HbA1c reduction (baseline of 8.28%): -2.09%, -2.37%, -2.46% vs -1.86%
  • Weight reduction (baseline of 93.7kg): -7.8kg, -10.3kg, -12.4kg vs -6.2kg
  • Percentage of patients achieving HbA1c less than 7%: 85.5%, 88.9%, 92.2% vs 81.1%
  • Percentage of patients achieving HbA1c less than 5.7%: 29.3%, 44.7%, 50.9%, vs 19.7%

In the treatment-regimen estimand (which represents the efficacy irrespective of adherence to the investigational drug or introduction of rescue therapy for persistent severe hyperglycemia), tirzepatide was associated with the following HbA1c and body weight reductions for the 5mg, 10mg, and 15mg doses vs semaglutide, respectively:

  • HbA1c reduction: -2.01%, -2.24%, -2.30% vs -1.86%
  • Weight reduction: -7.6kg, -9.3kg, -11.2kg vs -5.7kg
  • Percentage of patients achieving HbA1c less than 7%: 82.0%, 85.6%, 86.2% vs 79.0%
  • Percentage of patients achieving HbA1c less than 5.7%: 27.1%, 39.8%, 45.7% vs 18.9%

The most commonly reported adverse events across all treatment arms were gastrointestinal-related (ie, nausea, diarrhea, vomiting). Hypoglycemia less than 54mg/dL was reported in 0.6%, 0.2% and 1.7% of patients treated with tirzepatide 5mg, 10mg, and 15mg, respectively, and in 0.4% of those who received semaglutide.

Commenting on the results, Juan Pablo Frías, MD, Medical Director, National Research Institute and principal investigator of SURPASS-2, said: “Tirzepatide delivered clinically meaningful efficacy, beyond what has been seen with an existing medicine in the established GLP-1 receptor agonist class.”

Additional data from SURPASS-2 will be presented at the American Diabetes Association’s 81st Scientific Sessions.


Tirzepatide achieved superior A1C and body weight reductions across all three doses compared to injectable semaglutide in adults with type 2 diabetes. [press release]. Indianapolis, IN: Lilly Eli; March 4, 2021.