From the Guidelines
Imeglimin is not recommended as the first-line treatment for type 2 diabetes mellitus, as the current evidence prioritizes metformin due to its efficacy, safety, and cost-effectiveness, as stated in the most recent guidelines 1. The provided evidence does not support the use of Imeglimin as a preferred treatment option for type 2 diabetes. Instead, metformin is consistently recommended as the initial pharmacological agent for type 2 diabetes due to its long-standing evidence base for efficacy and safety, low cost, and extensive clinical experience. Key points to consider when treating type 2 diabetes include:
- Metformin as the preferred initial glucose-lowering medication for most people with type 2 diabetes, unless contraindicated or not tolerated 1.
- The importance of individualizing glycemic targets and glucose-lowering therapies, taking into account patient preferences, needs, and values 1.
- The need for comprehensive cardiovascular risk reduction as a major focus of therapy 1.
- The potential for combination therapy with additional oral or injectable agents to minimize side effects and achieve glycemic control 1. In the context of type 2 diabetes management, metformin is the preferred initial treatment option, and other medications, including Imeglimin, should only be considered if metformin is contraindicated or not tolerated, or if additional therapy is needed to achieve glycemic control 1.
From the Research
Efficacy of Imeglimin in Treating Type 2 Diabetes Mellitus
- Imeglimin has been shown to improve hemoglobin A1c and fasting plasma glucose levels in patients with type 2 diabetes mellitus, with a similar efficacy to metformin and sitagliptin 2.
- The mechanism of action of Imeglimin involves dual effects: amplification of glucose-stimulated insulin secretion and preservation of β-cell mass, as well as enhanced insulin action, including the potential for inhibition of hepatic glucose output and improvement in insulin signalling in both liver and skeletal muscle 3.
- Imeglimin has been observed to rebalance respiratory chain activity, reduce reactive oxygen species formation, and prevent mitochondrial permeability transition pore opening, resulting in reduced oxidative stress and prevention of cell death 3, 4.
- Imeglimin has also been shown to preserve β-cell mass in rodents with type 2 diabetes, and to prevent human endothelial cell death by inhibiting mitochondrial permeability transition without inhibiting mitochondrial respiration 4, 5.
Safety and Tolerability of Imeglimin
- Imeglimin has been reported to have a low incidence of adverse effects, especially hypoglycemia, in early human studies 2.
- A systematic review and meta-analysis of randomized clinical trials found that Imeglimin was safe and tolerable, with no treatment-emergent or serious adverse events, and improved glycemic control by reducing HbA1c and FPG 6.
- However, long-term evidence on the cardiovascular safety of Imeglimin is still lacking, and data on morbidity and mortality are limited 2.
Clinical Trials and Studies
- Several pivotal phase III trials have been completed, with evidence of statistically significant glucose lowering and a generally favourable safety and tolerability profile 3.
- A study in Zucker diabetic fatty (ZDF) rats found that Imeglimin treatment significantly improved glucose-stimulated insulin secretion and preserved islet β-cell mass, with a significant increase in insulin-positive β-cells 5.
- A systematic review and meta-analysis of randomized clinical trials found that Imeglimin safely improved glycemic control, but had no beneficial effects on insulin resistance or lipid parameters 6.