Tirzepatide superior to insulin glargine for reducing weight and blood sugar: SURPASS-4 trial

Delhi: The investigational diabetes drug tirzepatide led to superior blood sugar and body weight reductions than insulin glargine in patients with type 2 diabetes at increased cardiovascular risk, show results from SURPASS-4.

The 52-week SURPASS-4 trial is a randomized, parallel, open-label study that compared the safety and efficacy of tirzepatide to insulin glargine in adults with type 2 diabetes inadequately controlled with at least 1 and up to 3 oral antihyperglycemic medications (metformin, sulfonylureas or SGLT-2 inhibitors) and who have increased cardiovascular risk (N=2002; mean duration of diabetes, 11.8 years).

Patients were randomly assigned in the ratio of 1:1:1:3 to receive either tirzepatide 5mg, 10mg or 15mg or insulin glargine. The primary endpoint of the study was the change from baseline to week 52 in HbA1c. The study was meant to demonstrate that the 2 higher doses of tirzepatide (10mg and 15mg) were noninferior to insulin glargine.

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 units per day.

The trial is a part of phase 3 global clinical development program for tirzepatide, a novel, 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.

In the treatment-regimen estimand (representing efficacy irrespective of adherence to the investigational drug or introduction of rescue therapy for persistent severe hyperglycemia), tirzepatide was associated with the following HbA1c and body weight reductions for the 5mg, 10mg, and 15mg doses vs insulin glargine, respectively:

The most commonly reported adverse events across all treatment arms were gastrointestinal-related (ie, nausea, diarrhea, vomiting). Hypoglycemia less than 54mg/dL was reported in 6.7%, 5.5% and 6.5% of patients treated with tirzepatide 5mg, 10mg, and 15mg, respectively, and in 15% of those who received insulin glargine.

"These strong results reinforce our belief that tirzepatide has the potential to be an exciting treatment for people living with type 2 diabetes," said Mike Mason, president, Lilly Diabetes. "We look forward to meeting our goal of bringing an important new therapy to people living with this condition, including sharing more detailed results at scientific congresses and submitting to regulatory authorities later this year."

"Tirzepatide delivered impressive results in this study, providing superior A1C reductions compared to insulin glargine – as well as the addition of significant weight loss – in people with type 2 diabetes who have increased cardiovascular risk," said John Doupis, Director, Diabetes Division and Clinical Research Center, Iatriko Paleou Falirou Medical Center, Athens, Greece and Senior Investigator for SURPASS-4. "Type 2 diabetes is a complex condition that requires personalized approaches to treatment, and results from SURPASS-4 demonstrate the potential of tirzepatide to be an important option to help reduce A1C and weight for people with type 2 diabetes on one or up to three oral medicines."

The complete SURPASS-4 study data are being evaluated and additional results will be presented at the 57th Annual Meeting of the European Association for the Study of Diabetes and published in a peer-reviewed journal.

About tirzepatide

Tirzepatide is a 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 novel molecule. GIP is a hormone that may complement the effects of GLP-1 receptor agonists. 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.

Tirzepatide is in phase 3 development for blood glucose management in adults with type 2 diabetes and for chronic weight management. It is also being studied as potential treatments for non-alcoholic steatohepatitis (NASH) and heart failure with preserved ejection fraction (HFpEF).