The SURPASS program, which consists in part of SURPASS-3 and SURPASS-5, is testing the efficacy and safety of tirzepatide, a novel investigational once-weekly dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist.
Results of 2 phase 3 trials showed Eli Lilly’s tirzepatide significantly reduced glycated hemoglobin (A1C) and body weight among adults with type 2 diabetes (T2D). The SURPASS program, which consists in part of SURPASS-3 and SURPASS-5, is testing the efficacy and safety of tirzepatide, a novel investigational once-weekly dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist.
“In preclinical models, GIP has been shown to decrease food intake and increase energy expenditure therefore resulting in weight reductions, and when combined with a GLP-1 receptor agonist, may result in greater effects on glucose and body weight,” according to a company statement.
Tirzepatide functions by integrating the actions of both incretins into a single molecule and represents a new class of medicines studied for T2D treatment.
SURPASS-3, which lasted 52 weeks and compared the treatment with titrated insulin degludec, found the highest dose of tirzepatide (15 mg) reduced A1C by 2.37% and body weight by 12.9 kg or 13.9%. The 40-week SURPASS-5 trial compared tirzepatide with placebo while both were add-ons to titrated insulin glargine. In the latter trial, 15 mg of tirzepatide reduced A1C by 2.59% and body weight by 10.9 kg (11.6%) from baseline.
Furthermore, when receiving the highest dose, 62.4% of SURPASS-5 trial participants achieved an A1C of less than 5.7%. These participants had a mean duration of diabetes of 13.3 years. Both studies found the treatment’s safety profile was similar to the GLP-1 receptor agonist class, as gastrointestinal adverse events (nausea, diarrhea, vomiting) were most commonly reported and decreased as dosing continued.
The findings come just after newly reported data show that once-weekly treatment with 2.4 mg of Novo Nordisk’s semaglutide plus lifestyle intervention among individuals with overweight or obesity was associated with sustained, clinically relevant reductions in body weight. However, all patients who received the GLP-1 analogue in the global phase 3 Semaglutide Treatment Effect in People with Obesity (STEP) 1 program did not have T2D.
“Significantly lowering A1C levels and weight are high priorities throughout the T2D treatment journey, and the results we have seen from three SURPASS studies to date fuel our belief in tirzepatide's ability to meet those needs,” said Mike Mason, president of Lilly Diabetes.
Overall, the SURPASS program has enrolled more than 13,000 individuals with T2D across 10 clinical trials, 5 of which are global registration studies. Full results are expected to be announced later this year.
SURPASS-3 assessed 3 doses of tirzepatide (5 mg, 10 mg, and 15 mg) among patients with inadequate glycemic control on stable doses of metformin with or without a sodium-glucose cotransporter-2 (SGLT-2) inhibitor. All 1444 participants were insulin-naïve and had a mean duration of diabetes of 8.4 years, a baseline A1C of 8.17%, and a baseline weight of 94.3 kg. After 52 weeks, researchers found:
A total of 475 participants were randomized 1:1:1:1 in SURPASS-5 with a baseline mean A1C of 8.31%, weight of 95.2 kg, and insulin glargine dose of 37.6 units per day. Analyses revealed that after 40 weeks:
Complete data from both studies have yet to be evaluated. They will be presented at the ADA’s 81st Scientific Sessions and published in a peer-reviewed publication in 2021. Tirzepatide is also being studied as a potential treatment for nonalcoholic steatohepatitis.