Mini Review - (2019) Volume 10, Issue 11
Imeglimin is a new class of drug which has introduced recently. The molecular mechanisms are unknown, although imeglimin improves insulin sensitivity in humans. Pre-clinical studies had confirmed that imeglimin favouring lipid oxidation in liver and preserving mitochondrial function from oxidative stress, therefore normalizes glucose tolerance and insulin sensitivity. The main objective of this review article is to highlight updates of new class of drug which is imeglimin and generated a huge interest after recently conducted EASD at Barcelona.
Imeglimin; T2DM; New class of drug
Diabetes together with cardiovascular disease ranking among 10th leading cause of mortality and consider as one of the largest global health emergencies of this country [1,2]. The current global statistics indicate that 8.8% of the adult population has diabetes with slightly higher rates in men (9.1%) compared to women (8.4%) [1]. Type 2 Diabetes Mellitus (T2DM) is a chronic condition that associated with significant comorbidities. Understanding the pathophysiological derangements involved in the occurrence of diabetes and related comorbidities inessential to plan out successful prevention and control strategies.
Although several class of antidiabetic drug were available which has proven clinical effectiveness to control glycemic parameters in T2DM subjects but there always a search new therapeutic drug which offer additional benefits or works with different pathway as compare to existing therapies. The main objective of this review article is to highlight updates of new class of drug which is imeglimin and generated a huge interest after recently conducted EASD at Barcelona.
Imeglimin: A new class in T2DM management
Imeglimin is a very recently introduced drug which indicated for achieving glycemic control in Type 2 Diabetes Mellitus patients (T2DM). A new class of drug imeglimin having dual MoA. There were several in vitro trial which confirmed that three main pathophysiologic components of type 2 diabetes which were excess hepatic gluconeogenesis, impaired glucose uptake by muscle tissue and increased beta-cell apoptosis, were addressed by this new class of drug called imeglimin [3].
This new class of drug called GLIMIN or tetrahydrotriazene compound, which has demonstrated very robust efficacy in its phase 2 and phase 3 trials including elderly and CKD patients [4]. Clinical studies with imeglimin
A clinical study done by Pacini et al. [5] had confirmed that 7 days of imeglimin treatment significantly raised the insulin secretory response (ISR) to glucose by 112% (p=0.035), first-phase ISR by+110% (p=0.034) and second-phase ISR by+29% (p=0.031). This was a randomised, double blind, placebo control trial done in 33 type 2 diabetes subjects and positively conclude that mechanism of action of imeglimin explore its beneficial effect on beta-cell function.
Two dose ranging study was conducted with imeglimin to determine its effective dose [6,7]. Imeglimin 1500 mg twice daily was shown to be more effective and having more tolerability than compare to other possible doses.
In another 12 week randomised placebo control multicenter 12 week trial confirms the potential efficacy of the drug when added to maximum tolerable dose of metformin [8]. There were statistically significant reduction in HbA1c by 0.65% as compared to placebo which offers only 0.21% reduction in HbA1c. 60% patients had experienced with more that 0.5% decrease in HbA1c as compared to placebo where it was only 30%.
A large randomized, double-blind, placebo-controlled,12-week, multicenter parallel group study conducted in three different country and done among 170 patients had confirmed that imeglimin 1500 mg BD treatment in addition with sitagliptin 100 mg offers 0.6% reduction in HbA1c from baseline of 8.5% as compare to imeglimin+placebo treatment which offer only 0.12% reduction in HbA1c [9]. There was no significant difference between the groups with regard to C-reactive protein, triglycerides, systolic blood pressure and beta-cell function parameters such as pro-insulin/insulin ratio, c-peptide (ng/ml), insulin (uIU/ml) or homeostatic model assessment of insulin resistance.
Updates at EASD 2019
Ralph A. DeFranzo introduced the molecule and Dr Julie Dubourg MD, Paxel's medical director presented the TIMES clinical development study of imeglimin. It was by improving mitochondrial function in T2DM patients which improves insulin sensitivity as well as secretion. It also decreases hepatic glucose output. It corrects the mitochondrial dysfunction by restoring complex 2 activity and inhibiting complex 1 activity, leading to increased mitochondrial oxidation of complex 2 substrates (lipids).
There is decrease ROS overproduction and protecting mitochondria from excess oxidative stress especially beta cells are more sensitive to oxidative stress. Increase PGC1a, a master regulator of mitochondria biogenesis. It increases glucosedependent insulin secretion and beta-cell glucose sensitivity in drug-naive/withdrawn T2DM Pts. In conclusion slide Defranzo stated that imeglimin improves mitochondrial function and augments ATP production by enhancing flux through complex 2 of the mitochondrial respiratory chain. Dr. Dubourg reported that in TIMES 1 study in 213 T2DM over age 20 yrs at 24 weeks had 35.8% of achieved <7% HbA1c against 7.5% in placebo gp. An FBS drop of 19 mg/dl (p<0.0001) at 24 weeks. The results were consistent across the age group and across the CKD stage 1 and 2. There was no hypoglycemia in both arms. GI intolerance was 11.3% in drug arm versus 8.4% with placebo. Thus a great drug under trial at US, Europe and Japan with a very new site of action.
Further evidence is needed to support the long-term safety of imeglimin. In current T2DM treatment algorithm the place that imeglimin yet not firmly confirmed. More data regarding long term cardiovascular safety and tolerability data required to established imeglimin as potential and effective drug choice for T2DM patients.
Citation: Kumar S (2019) Imeglimin: Therapeutic Option for Achieving Glycemic Control. J Diabetes Metab 10:838. doi: 10.35248/2155-6156.19.10.838.
Received: 11-Oct-2019 Published: 04-Dec-2019, DOI: 10.35248/2155-6156.19.10.838
Copyright: © 2019 Kumar S . This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
