The much anticipated results from the SURPASS 2 clinical trial demonstrated reductions in A1c and body weight with tirzepatide that were significant and superior to those with semaglutide.
Tirzepatide, the novel injectable once-weekly dual glucose-dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 receptor agonist 1 (GLP-1 RA) led to superior reductions in baseline hemoglobin A1c (A1c) and body weight compared to GLP-1 RA semaglutide in patients with type 2 diabetes (T2D) on background treatment with metformin.
More than 90% (92%) of participants receiving tirzepatide reached an A1c <7% and up to 51% achieved an A1c <5.7%.
The findings, from the SURPASS 2 clinical trial sponsored by Eli Lilly, were simultaneously published on Friday, June 25, 2021, in The New England Journal of Medicine (NEJM)and presented in a late breaking poster presentation during the American Diabetes Association's® (ADA) 81st Scientific Sessions.
SURPASS 2, led by Juan Pablo Frias, MD, Medical Director of the National Research Institute, was a 40-week, multicenter, randomized, parallel, open-label trial designed to compare the efficacy and safety of 3 doses of tirzpeatide (5 mg, 10 mg, 15 mg) to semaglutide 1 mg adults with T2D inadequately controlled with ≥1500 mg/day metformin alone.
The primary objective, wrote Frias et al, was to demonstrate noninferiority in reduction of A1c with tirzepatide 10 and 15 mg compared to semaglutide 1 mg from baseline to week 40.
Key secondary endpoints included reductions noninferior to semaglutide in A1c from baseline for low-dose (5 mg) tirzepatide; superior reductions in body weight and A1c as well as a greater proportion of participants reaching A1c <7% for all 3 doses of terzepatide and greater percentages achieving A1c <5.7% for the 10 and 15 mg doses of tirzepatide.
SURPASS randomized 1 879 participants 1:1:1:1 to tirzepatide 5, 10, or 15 mg dose, or semaglutide 1 mg. Participants’ mean age was 56.6 years, mean A1c at baseline, 8.28%, mean baseline weight, 93.7 kg and BMI, 34.2 kg/m2. Average duration of T2D was 8.6 years.
Study authors report superior reductions from baseline in A1c and body weight for all 3 tirzepatide doses vs semaglutide. Specifically:
Estimated differences between tirzepatide groups and the semaglutide group were statistically significant for the 10 mg (−0.39 percentage points [95% CI, −0.51 to −0.26; P<.001]), and 15 mg (−0.45 percentage points [95% CI, −0.57 to −0.32; P<.001]) doses.
Frias et al also report that at all 3 doses, tirzepatide was noninferior and superior to semaglutide. Overall reductions in body weight from baseline were greater with tirzepatide vs semaglutide: (least-squares mean estimated treatment difference, −1.9 kg (5mg), −3.6 kg (10 mg), and −5.5 kg (15 mg); P<.001 for all comparisons).
Hypoglycemia (blood glucose <54 mg/dL) among all treated patients were reported to be low.
The most commonly reported side effects across treatment arms were gastrointestinal in nature and mostly mild-to-moderate.
Evaluation of an additional exploratory endpoint found that all 3 doses of tirzepatide led to reductions from baseline in fasting lipids including for the 15 mg dose a reduction in triglycerides of nearly 25%.
These results, which will also be featured during an ADA-sponsored symposium on Tuesday, June 29, showed that all three tirzepatide doses achieved greater A1C and weight reductions compared to semaglutide.
SURPASS-2 is the second of five global registration studies for tirzepatide in type 2 diabetes, all of which have been completed. Lilly intends to submit the full registration package to regulatory authorities by the end of 2021.
SURPASS 2 results also will be featured during an ADA-sponsored symposium, Next Chapter in Incretin-Based Therapies—Tirzepatide, a Novel Dual GIP/GLP-1 Receptor Agonist—Results from the First Phase 3 SURPASS Clinical Trials , on Tuesday, June 29, 2021, from 8-9:30 am, EST.