The results of the SURPASS-2 clinical trial evaluating the effects of tirzepatide in patients with type 2 diabetes showed that the trial treatment resulted in superior reductions in hemoglobin A1c (HbA1c) and body weight compared to injectable semaglutide.
The 40-week SURPASS-2 study (ClinicalTrials.gov: NCT03987919) is part of a global phase 3 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 effects of both incretins into a single molecule. The multicentre, randomized, parallel, open study compared the safety and efficacy of tirzepatide with semaglutide in adults with type 2 diabetes who were inadequately controlled with metformin alone at least 1500 mg / day (N = 1879; mean duration of diabetes 8.6 years ). .
The patients were randomly assigned 1: 1: 1: 1 to either tirzepatid 5 mg, 10 mg or 15 mg or semaglutide 1 mg. The primary endpoint of the study was HbA1c change from baseline at week 40. The study was supposed to show that the 2 higher doses of tirzepatide (10 mg and 15 mg) were not inferior to semaglutide.
The efficacy estimate and results (showing efficacy before study drug discontinuation or rescue therapy was initiated for persistent severe hyperglycemia) for tirzepatide 5 mg, 10 mg, and 15 mg versus semaglutide included the following:
- HbA1c reduction (baseline of 8.28%): -2.09%, -2.37%, -2.46% versus -1.86%
- Weight reduction (baseline of 93.7 kg): -7.8 kg, -10.3 kg, -12.4 kg versus -6.2 kg
- Percentage of patients who achieve HbA1c below 7%: 85.5%, 88.9%, 92.2% versus 81.1%
- Percentage of patients who achieved HbA1c below 5.7%: 29.3%, 44.7%, 50.9% versus 19.7%
In the treatment regimen estimate (which represents efficacy regardless of adherence to the investigational drug or the introduction of rescue therapy for persistent severe hyperglycemia), tirzepatide was associated with the following HbA1c and body weight reductions for the doses of 5 mg, 10 mg and 15 mg vs. semaglutide :
- HbA1c reduction: -2.01%, -2.24%, -2.30% versus -1.86%
- Weight reduction: -7.6 kg, -9.3 kg, -11.2 kg versus -5.7 kg
- Percentage of patients who achieved HbA1c below 7%: 82.0%, 85.6%, 86.2% versus 79.0%
- Percentage of patients who achieved HbA1c below 5.7%: 27.1%, 39.8%, 45.7% versus 18.9%
The most frequently reported adverse events in all treatment arms were gastrointestinal (ie, nausea, diarrhea, vomiting). Hypoglycemia of less than 54 mg / dL was observed in 0.6%, 0.2% and 1.7% of the patients treated with 5 mg, 10 mg and 15 mg of tirzepatide and 0.4% of the patients treated with semaglutide reported.
Commenting on the results, Juan Pablo Frías, MD, Medical Director of the National Research Institute and Principal Investigator of SURPASS-2, said: “Tirzepatid provided clinically meaningful efficacy beyond what is seen with an existing drug in the established GLP-1 receptor became an agonist class. ”
Additional data from SURPASS-2 will be presented at the 81st Scientific Sessions of the American Diabetes Association.
reference
Tirzepatid achieved superior reductions in A1C and body weight compared to injectable semaglutide in adults with type 2 diabetes at all three doses. [press release]. Indianapolis, IN: Lilly Eli; March 4, 2021.
