Lilly’s Tirzepatide Significantly Reduces A1C, Body Weight Versus Insulin Glargine

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Lilly’s Tirzepatide Significantly Reduces A1C, Body Weight Versus Insulin Glargine



Newly announced topline results from Eli Lilly’s SURPASS-4 trial program show the company’s investigational diabetes agent, tirzepatide, significantly reduced blood glucose levels and body weight better than insulin glargine in adult patients with type 2 diabetes. 

Tirzepatide is a once-weekly dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist. Given its design, tirzepatide is said to represent “a new class of medicines” for type 2 diabetes. 

Preclinical studies show GIP decreases food intake and increases energy expenditure, subsequently leading to weight loss. In combination with GLP-1 receptor agonist, GIP may also lead to even greater blood glucose and weight effects. 

Currently, Eli Lilly’s tirzepatide is in Phase III development for type 2 diabetes and weight management. Additional studies look into the agent’s effects on non-alcoholic steatohepatitis (NASH) and heart failure with preserved ejection fraction (HFpEF).

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In the open-label SURPASS-4 trial, investigators compared the safety and efficacy of tirzepatide at 5 mg, 10 mg, and 15 mg versus titrated insulin glargine in over 2,000 patients with type 2 diabetes. Participants in this trial were at an increased risk of cardiovascular adverse events and were being treated with one to three oral antihyperglycemic therapies, such as sulfonylurea, metformin, or an SGLT-2 inhibitor.

At baseline, participants in the trial had diabetes for an average of 11.8 years. The average baseline A1C, a marker for blood glucose, was 8.52%. Additionally, the average weight at baseline was 90.3 kilograms. Over 85% of patients in the study had a history of cardiovascular events. 

Compared with titrated insulin glargine, treatment with tirzepatide at all three doses resulted in significant declines in A1C and body weight from baseline to 52 weeks. The highest tirzepatide dose resulted in an A1C reduction of approximately 2.58% and a decrease in body weight of 11.7 kg (25.8 lb.; 13.0%) versus insulin glargine at the 52-week follow-up period.

The safety profile of tirzepatide was considered consistent with the GLP-1 receptor agonist class previously reported in patients with type 2 diabetes. The most commonly reported adverse events included gastrointestinal side effects that were mild to moderate in severity. These side effects typically occurred during the treatment escalation period but generally decreased over time. 

“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,” said John Doupis, M.D., Ph.D., senior SURPASS-4 Investigator and Director of the Diabetes Division and Clinical Research Center at the Iatriko Paleou Falirou Medical Center in Athens, Greece.

In March, findings from the Phase III, 40-week SURPASS-2 study showed tirzepatide at 15 mg led to a significantly greater A1C reduction and reduction in body weight compared with semaglutide in patients with type 2 diabetes. 

Despite the findings showing tirzepatide was superior to semaglutide, Novo Nordisk continues full-steam ahead on developing semaglutide as an anti-obesity therapy. 

Data published in the New England Journal of Medicine in March showed once-weekly semaglutide at 2.4 mg for 68 weeks led to clinically meaningful and sustained weight loss in adults with obesity compared with lifestyle alone. These findings prompted Novo Nordisk to recently apply for a priority review voucher for a New Drug Application the company submitted to the U.S. Food and Drug Administration in December.


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