FDA Approves Tirzepatide Injection for Adults With Type 2 Diabetes

The FDA has approved tirzepatide (Mounjaro; Eli Lilly and Company), a novel, dual-targeted treatment shown to improve glycemic control in adults with type 2 diabetes. The once-weekly glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist is indicated as an adjunct to diet and exercise in adults with type 2 diabetes.¹

The drug has not been studied in patients with a history of pancreatitis and is not indicated for use in patients with type 1 diabetes mellitus, according to Eli Lilly.

“Type 2 diabetes is a chronic and progressive condition that requires continued innovation to help people manage their blood glucose and weight," said Mike Mason, president, Lilly Diabetes, in a press release. "[The] FDA approval underscores our commitment to the discovery and development of new treatment pathways, and we are thrilled to bring this new and innovative treatment option to people living with type 2 diabetes.”

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.

Clinical trial data show tirzepatide is effective at improving blood sugar more effectively than other diabetes treatments. The SURPASS trials showed encouraging results with tirzepatide in various patient populations. The drugs were tested as either a stand-alone therapy or as an add-on to other medications.²

SURPASS-1 was a randomized, controlled, double-blind trial comparing the results of tirzepatide with placebo in adults with uncontrolled type 2 diabetes. 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.²

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 adverse effects (AEs) were balanced between the groups. 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.²

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.

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.

SURPASS-5 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, 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.

Treatment with tirzepatide also resulted in an average weight loss of 15 pounds more than placebo when both were used with insulin, with an average weight loss with the 15 mg dose of 12 pounds more than semaglutide, 29 pounds more than insulin degludec and 27 pounds more than insulin glargine.

"Mounjaro delivered superior and consistent A1C reductions against all of the comparators throughout the SURPASS program, which was designed to assess Mounjaro's efficacy and safety in a broad range of adults with type 2 diabetes who could be treated in clinical practice. The approval of Mounjaro is an exciting step forward for people living with type 2 diabetes given the results seen in these clinical trials," SURPASS program investigator Juan Pablo Frías, MD, medical director, National Research Institute, said in a press release.

References

1. FDA approves Lilly's Mounjaro™ (tirzepatide) injection, the first and only GIP and GLP-1 receptor agonist for the treatment of adults with type 2 diabetes. Eli Lilly. News release. May 13, 2022. https://investor.lilly.com/news-releases/news-release-details/fda-approves-lillys-mounjarotm-tirzepatide-injection-first-and

2. Antrim, A. Tirzepatide Shows Significant Improvements in Glycemic Control, Weight Loss Among Patients with Type 2 Diabetes. Pharmacy Times. June 29, 2021. https://www.pharmacytimes.com/view/tirzepatide-shows-significant-improvements-in-glycemic-control-weight-loss-among-patients-with-type-2-diabetes