Try our mobile app
INDIANAPOLIS, Oct. 19, 2021 /PRNewswire/ -- Adults with type 2 diabetes with increased cardiovascular (CV) risk experienced superior A1C and body weight reductions from baseline across all three doses of tirzepatide compared to titrated insulin glargine in detailed results from Eli Lilly and Company's (NYSE: LLY) SURPASS-4 clinical trial, which were published today in The Lancet. At 52 weeks, the highest dose of tirzepatide led to an A1C reduction of 2.58 percent and reduced body weight by 11.7 kg (-25.8 lb., -13.0 percent) compared to results for those treated with insulin glargine (A1C reduction of 1.44 percent and weight gain of 1.9 kg [+4.2 lb., +2.2 percent]) for the efficacy estimand.i,1
SURPASS-4 is the largest and longest clinical trial completed to date of the phase 3 program studying tirzepatide as a potential treatment for type 2 diabetes. The primary endpoint was measured at 52 weeks, with participants continuing treatment up to 104 weeks or until study completion. The completion of the study was triggered by the accrual of major adverse cardiovascular events (MACE) to assess CV risk. In newly published data from the treatment period after 52 weeks, participants taking tirzepatide maintained A1C and weight control for up to two years.
The overall safety profile of tirzepatide, assessed over the full study period, was consistent with the safety results measured at 52 weeks, with no new findings up to 104 weeks. Gastrointestinal side effects were the most commonly reported adverse events, usually occurring during the escalation period and then decreasing over time.
"We are encouraged by the continued A1C and weight control that participants experienced past the initial 52 week treatment period and up to two years as we continue to explore the potential impact of tirzepatide for the treatment of type 2 diabetes," said John Doupis, M.D., Ph.D., Director, Diabetes Division and Clinical Research Center, Iatriko Paleou Falirou Medical Center, Athens, Greece and Senior Investigator for SURPASS-4.
Tirzepatide is a novel investigational 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, representing a new class of medicines being studied for the treatment of type 2 diabetes.
SURPASS-4 was an open-label global trial comparing the safety and efficacy of three tirzepatide doses (5 mg, 10 mg and 15 mg) to titrated insulin glargine in 2,002 adults with type 2 diabetes with increased CV risk who were treated with between one and three oral antihyperglycemic medicines (metformin, a sulfonylurea or an SGLT-2 inhibitor). Of the total participants randomized, 1,819 (91%) completed the primary 52-week visit and 1,706 (85%) completed the study on treatment. The median study duration was 85 weeks and 202 participants (10%) completed two years.
Study participants had a mean duration of diabetes of 11.8 years, a baseline A1C of 8.52 percent and a baseline weight of 90.3 kg. More than 85 percent of participants had a history of cardiovascular events. In the insulin glargine arm, the insulin dose was titrated following a treat-to-target algorithm with the goal of fasting blood glucose below 100 mg/dL. The starting dose of insulin glargine was 10 units per day, and the mean dose of insulin glargine at 52 weeks was 43.5 units per day.
SURPASS-4 achieved each of its primary and key secondary endpoints. All three doses of tirzepatide (5 mg, 10 mg and 15 mg) led to statistically significant and superior A1C and body weight reductions compared to insulin glargine for both estimandsii at 52 weeks (the primary endpoint). Specifically, the efficacy estimand results showed:
