Tirzepatide Shows Significant Improvements in Glycemic Control, Weight Loss Among Patients with Type 2 Diabetes

The results from the first phase 3 SURPASS trials showed promising results with tirzepatide in patients with type 2 diabetes.

A review of data from the SURPASS trials found that tirzepatide resulted in significant improvements in hemoglobin A1c (HbA1c) as well as weight management, according to a presentation at the American Diabetes Association’s 81st Scientific Sessions.

Tirzepatide belongs to the gastric inhibitory polypeptide (GIP) glucagon-like peptide-1 (GLP-1) co-agonist class of medications, according to presenter Danial Drucker, MD. GLP-1 treatments have a number of approvals for diabetes and obesity, and Drucker said between 50% and 60% of patients achieve weight loss goals with these treatments.

Tirzepatide is a multi-functional peptide based on the native GIP peptide sequence, although it has been modified to bind to both GIP and GLP-1 receptors. It has a mean half-life of approximately 5 days, making once-weekly dosing possible. Drucker said clinical trials in patients with type 2 diabetes have shown “very impressive data,” and the adverse effect (AE) profile is not markedly different from other types of reports with other molecules in this drug class.

Other presenters outlined the results from the SURPASS trials, all of which showed encouraging results with tirzepatide in various patient populations. The SURPASS-1 trial was a randomized, controlled, double-blind trial comparing the results of tirzepatide with placebo in adults with uncontrolled type 2 diabetes, according to presenter Carol Wysham, MD, a clinical professor of medicine at the University of Washington School of Medicine.

In the trial, 705 patients were screened and 478 were randomized between groups to receive either tirzepatide or a placebo. Within the tirzepatide group, patients received either 5 mg, 10 mg, or 15 mg, and all 3 doses were associated with a superior reduction in A1c compared to placebo.

Participants receiving the highest dose achieved a reduction of 2.7%, and between 87% and 92% of tirzepatide-treated patients achieved an A1c target of less than 7%. Furthermore, between 13% and 27% of patients receiving tirzepatide achieved weight loss of at least 15% of body weight, and overall AEs were balanced between the groups. A single death occurred in the placebo group because of myocardial infarction, according to the researchers.

Based on these findings, Wysham said once-weekly tirzepatide helped manage type 2 diabetes that was inadequately controlled with diet and exercise alone. Investigators found robust reductions in glycemic control as well as body weight, and normoglycemia (defined as <5.7%) was achieved in at least one-third of participants.

The SURPASS-2 trial found similarly encouraging results comparing tirzepatide with once-weekly semaglutide as an add-on therapy to metformin in patients with type 2 diabetes. Approximately 470 patients were included in each of the 4 treatment groups and between 94% and 96% completed the study.

Discontinuations were slightly higher in the tirzepatide arms compared to the semaglutide arm, said presenter Juan Frias, MD, medical director and principal investigator of the National Research Institute in Los Angeles. Frias said the majority of discontinuations were attributed to AEs and the majority of deaths were related to COVID-19.

Reductions in A1c were observed as early as week 4 in the tirzepatide group and ranged from -0.2% to -0.6% with the 15 mg dose compared to semaglutide. A greater proportion of tirzepatide patients achieved HbA1c goals at 40 weeks compared to semaglutide and a significantly greater proportion of patients in the tirzepatide arm achieved their weight loss goals.

Based on these findings, Frias said once weekly tirzepatide demonstrated superior and clinically meaningful improvements in glycemic control as well as a significant reduction in body weight. Normoglycemia was achieved in up to 51% of participants.

Finally, Michelle Welch, MD, FACE, president of Diabetes and Metabolism Specialists in San Antonio, discussed SURPASS-5, which compared the efficacy and safety of 3 tirzepatide doses versus placebo as an add-on to insulin glargine with or without metformin. Participants had an average age of 60 years, and 44% were female, 80% were Caucasian, and 18% were Asian. The average length of diabetes was 13.3 years with a baseline A1c of 8.3%.

Over the 40-week study period, investigators observed between a 2.2% and 2.9% decrease in A1c in the tirzepatide arm. In the arm receiving placebo and titrated insulin glargine, Welch said there was an expected increase in body weight with a corresponding decrease in the tirzepatide arm. Between 8% and 32% of patients achieved 15% or more body weight loss.

All doses of tirzepatide were superior to placebo at 40 weeks for change from baseline in HbA1c as well as change from baseline in body weight. The most common AEs with tirzepatide were gastrointestinal in nature, were mostly mild to moderate in severity, and decreased over time. Welch concluded that in patients with type 2 diabetes treated with basal insulin glargine and with or without metformin, tirzepatide was an effective treatment to improve glycemic control and lower body weight.

Drucker agreed, adding that tirzepatide is a promising treatment.

“A substantial number of people are having their glucose control normalized on this therapy,” Drucker concluded.

REFERENCE

Drucker D, Wysham C, Frias J, Giorgino F, Welch M. Next Chapter in Incretin-Based Therapies–Tirzepatide, a Novel Dual GIP/GLP-1 Receptor Agonist–Results from the First Phase 3 SURPASS Clinical Trials. Presented at American Diabetes Association 81st Scientific Sessions. June 29, 2021. Accessed June 29, 2021. https://ada2021.org/live-stream/19772900/Next-Chapter-in-Incretin-Based-TherapiesTirzepatide-a-Novel-Dual-GIPGLP-1-Receptor-AgonistResults-from-the--First-Phase-3-SURPASS-Clinical-Trials-Includes-Live-Video-Question-and-Answer-Period