Tirzepatide, a novel drug that acts via two related but separate pathways of glucose control, produced positive effects in top-line results from the phase 3, placebo-controlled study SURPASS-1 in 478 adults with type 2 diabetes, according to a December 9 press release from the manufacturer, Lilly.
The tirzepatide molecule exerts agonist effects at both the glucose-dependent insulinotropic polypeptide (GIP) receptor and the glucagon-like peptide-1 (GLP-1) receptor, and has been called a “twincretin” for its activity encompassing two different incretins. Phase 2 trial results caused excitement, with one physician calling the data “unbelievable” when reported in 2018.
Commenting on the new trial, Julio Rosenstock, MD, said in the Lilly statement: “The study took a bold approach in assessing A1c targets. Not only did nearly 90% of all participants taking tirzepatide meet the standard A1c goal of less than 7%, more than half taking the highest dose also achieved an A1c less than 5.7%, the level seen in people without diabetes — an unprecedented finding and unique endpoint in trials evaluating glucose-lowering agents.”
Rosenstock is principal investigator of SURPASS-1 and director of the Dallas Diabetes Research Center.
SURPASS-1 Results: Tirzepatide Patients Lost Up to 20 lb in Weight
In the study, patients had been recently diagnosed with type 2 diabetes (average duration, 4.8 years) and 54% were treatment-naive. Average baseline A1c was 7.9% and mean weight was 85.9 kg (189 lb).
Patients started on a subcutaneous injectable dose of tirzepatide of 2.5 mg per week, which was titrated up to the final dose — 5, 10, or 15 mg — in 2.5-mg increments given as monotherapy for 40 weeks and compared with placebo.
Treatment with tirzepatide resulted in average reductions in A1c from baseline that ranged from 1.87% to 2.07%, depending on the dose, and were all significant compared with an increase of 0.4% with placebo.
The percentage of patients whose A1c fell to normal levels (less than 5.7%) ranged from 30.5% to 51.7%, compared with 0.9% among controls, and again, was significant for all doses.
Patients treated with tirzepatide also lost weight. Average weight reductions after 40 weeks were significant and ranged from 7.0 to 9.5 kg (15 to 21 lb) compared with an average loss of 0.7 kg (1.5 lb) among patients who received placebo.
“Tirzepatide delivered impressive A1c and weight reductions for people with type 2 diabetes in this trial, confirming and building upon the phase 2 data,” added Rosenstock.
The most common adverse events were gastrointestinal-related and mild to moderate in severity, and usually occurred during dose escalation.
The full results of SURPASS-1 will be presented at the American Diabetes Association 81st Scientific Sessions and published in a peer-reviewed journal in 2021.
SURPASS-1 is one of eight phase 3 studies investigating the drug, including five registration studies. Reports on findings from the remaining seven studies should appear during the next year, says the company.