Promising Results In A Phase 3 First-in-Class Oral Diabetic Drug

How does Imeglimin perform in combination with metformin in patients with type 2 diabetes?

Imeglimin is the first in a new tetrahydrotriazine-containing class of oral antidiabetic agents, the glimins. Imeglimin decreases hepatic glucose production, increases muscle glucose uptake, and improves pancreatic glucose-dependent insulin secretion.

Previous studies have demonstrated imeglimin to be as effective as metformin in improving glycemia. Since metformin is the preferred first-line therapy for type 2 diabetes, the current study examined the efficacy, safety, and tolerability of Imeglimin in combination with metformin in patients with type 2 diabetes inadequately controlled with metformin alone.

In an ever-expansive drug field, it is important that providers are the first to know about promising drugs making their way through the pipeline. According to a recent press briefing, held by Poxel and Sumitomo Dainippon Pharma Co., it was signaled that their newest drug, Imeglimin, has shown positive results in the 3rd phase of the clinical trials. The 3rd phase of clinical trials of a drug is to establish safety and efficacy of the medication in a population of around 3,000. If Imeglimin becomes a certified and marketable medication, it will be the first of its class. Imeglimin is an oxidative phosphorylation blocker that has 3 mechanisms of action. Imeglimin targets the liver and blocks hepatoneogenesis, increases glucose reuptake in the muscles, and finally, restores normal insulin secretion.

The TIMES 3 study is a double blinded, randomized control study that took place for 16 weeks. During this time, 215 Japanese participants, whose diabetes was not fully controlled with insulin alone, were split into two cohorts. The first cohort were given 1,000 mg of Imeglimin twice daily in combination with insulin, while the second cohort were given insulin and a placebo control. According to the chief medical officer Christophe Arbet-Engels, MD, PhD., who gave a press briefing on the medication, Imeglimin has shown to be a viable option for significantly reducing A1C in patients with diabetes, and has shown to have a great tolerability profile.

According to the test trial results, the trials achieved statistical significance in both the primary and secondary endpoints (P<.0001). The primary endpoint was defined as a change in A1C from baseline vs. placebo after 16 weeks. The mean placebo-corrected A1C change measured to be -0.6% according to the press release. In a 2017 press release at the European Association for the Study of Diabetes, Endocrine Today reported on the Phase 2b data demonstrating the efficacy and safety of Imeglimin. A significant dose-dependent reduction in the A1C measure was reported among the participants in this phase.

As stated above, the A1C reduction was dose dependent. The dosage strengths 500 mg and 1000 mg showed a reduction of 0.52% and 0.94%, respectively. A1C reduction analysis of the strengths 1,000 mg and 1,500 mg showed a reduction of 0.94% and 1.0%, respectively. According to researchers, additional benefits exhibited in patients on 1,000 mg and 1,500 mg of Imeglimin included a significant reduction in both glycated albumin and percentage of patients reaching an A1C below 7%. Poxel and Sumitomo Dainippon Pharma Co. anticipate a full release of the trial data in an upcoming scientific press release. Secondary endpoints of the 16-week trial are under further analysis with modifications to the clinical trial. The modifications of the trial include an extension of 20 weeks to 16 weeks of the original trial, and it will become an open-label trial, rather than the double-blinded randomized control trial.

The significance of the recent data cannot be overstated. Diabetes is an increasingly prevalent disease that is in need of cutting-edge discoveries with equally safe medications. With the new development of Imeglimin, there is renewed hope in the maintenance of diabetes mellitus with resistance to insulin therapy.  

Practice Pearls

• Imeglimin is a new drug that has shown promise in the reduction of the overall A1C in patients whose insulin therapy is inadequate
• Although further testing is currently underway, the safety profile of Imeglimin has shown promise with minimal side effects
• A1C reduction has been shown to be dose dependent, with doses of 1,000 mg and 1,500 mg showing great promise in multiple diabetic aspects

Reference:

“The Efficacy and Safety of Imeglimin as Add-on Therapy in Patients With Type 2 Diabetes Inadequately Controlled With Metformin Monotherapy,” Pascale Fouqueray, MD1⇓, Valdis Pirags, MD2, Silvio E. Inzucchi, MD3, Clifford J. Bailey, PHD4, Guntram Schernthaner, MD5, Michaela Diamant, MD6 and Harold E. Lebovitz, MD Diabetes Care 2013 Mar; 36(3): 565-568.

https://doi.org/10.2337/dc12-0453

Usif Darwish, PharmD Candidate, Florida A&M University, College of Pharmacy & Pharmaceutical Sciences