The latest results from SURPASS-4, the longest and largest completed SURPASS trial to date, showed consistent activity in maintaining A1C and weight control in the almost two years it ran. SURPASS-4 is part of the Phase III trial evaluating tirzepatide as a possible treatment for type 2 diabetes.
In the open-label, global study, Eli Lilly researchers compared the efficacy and safety of three tirzepatide doses — 5 mg, 10 mg, and 15 mg — against titrated insulin glargine in 2,002 adults diagnosed with type 2 diabetes with increased cardiovascular (CV) risk and receiving one to three oral drugs such as metformin, sulfonylurea, or an SGLT-2 inhibitor. Participants had a mean duration of 11.8 years with diabetes, recording a baseline weight of 90.3 kg and A1C of 8.52%. Over 85% had a history of CV events.
At the end of the two-year trial, SURPASS-4 hit all of its primary and secondary endpoints, and all three doses led to significant and superior A1C and body weight reductions, as opposed to insulin glargine, when evaluated at 52 weeks and then later at 104 weeks. Hypoglycemia of less than 54 mg/dL was observed in 8.8%, 6.1%, and 8% of participants (receiving 5 mg, 10 mg, and 15 mg of tirzepatide, respectively), compared to 19.1% in those who received insulin glargine.
Other aspects of the study, covering adverse events, safety, and the presence of high-density lipoprotein, also demonstrated the drug’s superiority over the current treatment being used.
Diabetes, a chronic disease that happens when the body fails to produce insulin, affects one in 10 Americans, or 34 million. The most common type, Type 2 diabetes, accounts for as much as 95% of all diabetes cases in the U.S. alone.
“Given the progressive nature of type 2 diabetes, evaluating the positive efficacy results we have seen with tirzepatide over longer periods of time is important. Throughout the length of SURPASS-4, tirzepatide delivered robust improvements in blood glucose levels, significant weight loss and consistent safety results in adults with type 2 diabetes and increased cardiovascular risk,” said Jeff Emmick, M.D., Ph.D., vice president for product development, at Eli Lilly and Company, in a statement.
Tirzepatide is a once-weekly, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist that works by integrating incretin actions into one molecule. GIP is a hormone that can complement the effects of GLP-1 and, in preclinical models, has shown to help reduce food intake and boost energy expenditure, thus, resulting in significant weight reductions.