The dual GLP-1/GIP receptor agonist tirzepatide is currently being evaluated in Phase III clinical trials. In adult type 2 diabetics at increased cardiovascular risk, tirzepatide resulted in superior HbA1c and body weight reductions compared with titrated insulin glargine.
URPASS-4 is an open-label global study comparing the safety and efficacy of three doses of tirzepatide (5 mg, 10 mg and 15 mg) with titrated insulin glargine in more than 2000 people with type 2 diabetes who are at increased cardiovascular risk and are being treated with one to three oral antihyperglycemic agents (metformin, a sulfonylurea, or an SGLT-2 inhibitor).
Study participants had a mean diabetes duration of 11.8 years, baseline HbA1c at 8.52%, and body weight at baseline of 90.3 kg. Over 85% of participants had a history of cardiovascular events. At the highest tirzepatide dose, 90.7% of participants achieved an HbA1c of less than 7% – the American Diabetes Association’s recommended target for diabetics – after 52 weeks, and 43.1% achieved an HbA1c of less than 5.7%. This corresponds to an HbA1c reduction of 2.58%. During the same period, an average body weight reduction of 11.7 kg (13.0%) was achieved.
In the insulin glargine group, insulin dose was titrated according to a treat-to-target algorithm, with the goal of maintaining 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 after 52 weeks was 43 units per day. In those treated with insulin glargine, a 1.44% reduction in HbA1c and an average weight loss of 1.9 kg were achieved after 52 weeks.
The overall safety profile of tirzepatide in this patient population was comparable to the glucagon-like peptide-1 (GLP-1) receptor agonist class. Gastrointestinal adverse events were the most commonly reported adverse events, usually occurring during the escalation phase and then decreasing over time.
Source: “Lilly’s tirzepatide achieves all primary and key secondary study outcomes against insulin glargine in adults with type 2 diabetes and increased cardiovascular risk in SURPASS-4 trial,” 05/20/2021.
CARDIOVASC 2021; 20(2): 33
