At the 56th annual European Association for the Study of Diabetes (EASD) 2020 meeting, positive results have been discussed for the novel oral hypoglycemic drug imeglimin, which is currently under development for the treatment of type 2 diabetes (T2D). The drug is of a novel structure and mechanism, establishing imeglimin as a first-in-class for the ‘glimins.’ Imeglimin targets key defects in T2D by improving insulin secretion and insulin sensitivity by a unique mechanism of action targeting mitochondrial bioenergetics. TIMES 3 is a Phase III trial that aimed to confirm the efficacy and safety of imeglimin 1,000mg orally administered twice daily versus placebo, in combination with insulin in Japanese T2D patients who are inadequately controlled by insulin monotherapy. This novel therapy offers physicians a further therapeutic option for T2D patients who have been poorly responsive to other anti-diabetic therapies, particularly for Japan where oral therapies are highly anticipated, as there is a general avoidance of, and poor patient compliance with, subcutaneously administered drugs. GlobalData predicts that imeglimin will be able to obtain a significant share of the Japanese T2D market, particularly from the injectable T2D therapies, such as glucagon-like peptide-1 receptor agonists (GLP-1RAs), and become an established therapy for T2D in Japan.
This study was a Phase III multicenter, randomised, double-blind, placebo-controlled trial in Japanese patients with T2D inadequately controlled by insulin monotherapy. Patients were randomised 1:1 into the two arms of the trial, either imeglimin 1,000mg or placebo twice daily, in addition to their ongoing insulin therapy. The study design also included a 16-week double-blind treatment period followed by a 36-week open-label extension period on imeglimin for all patients, and the primary efficacy endpoint was the placebo-corrected reduction in HbA1c from baseline to Week 16. Trial results demonstrated that at Week 16, imeglimin significantly decreased HbA1c (difference vs placebo: -0.60%; p < 0.0001). In patients receiving imeglimin, reductions in HbA1c at Week 16 were maintained to Week 52 (difference vs baseline: -0.64%), and changing from placebo to imeglimin resulted in a similar reduction in HbA1c levels (difference vs baseline: 0.54%). During the double-blind treatment period, the incidence of treatment-emergent adverse events was similar between the two groups of the study, placebo and imeglimin, and the incidence of hypoglycemia was balanced between the two groups with no incidence of severe hypoglycemia across the 52-week study period.
The study demonstrates that imeglimin, in combination with insulin, produces clinically significant glycemic control without increasing the risk of hypoglycemia. The study proves that imeglimin is a consistent and efficacious novel T2D therapy, which could be utilised in order to achieve improved disease management in patients with T2D. Key opinion leaders (KOLs) interviewed by GlobalData have expressed the need for a therapy that offers a novel mechanism of action and can be used effectively in combination with existing therapies to achieve an optimised, or significantly improved, glycemic control. Imeglimin, in combination with insulin, has been demonstrated as likely to achieve this and will certainly gain a significant market share in the oral anti-diabetic market.