Imeglimin is an oral medication for managing type 2 diabetes. It is the first in a new class of drugs known as “glimins,” designed to address the underlying metabolic issues associated with this condition. This medication offers a distinct approach to improving blood sugar control in adults with type 2 diabetes.
How Imeglimin Works
Imeglimin exhibits a dual mechanism of action, targeting two main aspects of type 2 diabetes: improving insulin secretion and enhancing insulin sensitivity. It amplifies glucose-stimulated insulin secretion (GSIS) from pancreatic beta cells, helping the pancreas release more insulin when blood glucose levels are high. This action also contributes to the preservation of beta-cell mass, which can deteriorate in type 2 diabetes.
The medication also improves insulin action in peripheral tissues, such as muscle and liver. This includes a reduction in hepatic glucose output, meaning the liver produces less glucose, and an improvement in insulin signaling within liver and skeletal muscle cells. These combined effects help the body use insulin more effectively to lower blood sugar.
At a cellular level, imeglimin’s mechanism involves correcting mitochondrial dysfunction, a factor implicated in the development of type 2 diabetes. It rebalances respiratory chain activity, which leads to reduced reactive oxygen species formation, decreasing oxidative stress and preventing cell death. In pancreatic islet cells, imeglimin enhances glucose-stimulated ATP generation, which may contribute to increased insulin secretion.
Treating Type 2 Diabetes
Clinical trials have shown that imeglimin leads to significant reductions in glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG) levels. For instance, in some studies, imeglimin monotherapy reduced HbA1c by approximately 0.5-0.9%.
This medication can be used as a monotherapy, or as an adjunct to diet and exercise to improve glycemic control. It can also be combined with other anti-diabetic drugs, such as metformin or dipeptidyl peptidase-4 (DPP-4) inhibitors, to further enhance blood sugar control. When added to sitagliptin or metformin, imeglimin 1,500 mg twice daily resulted in HbA1c reductions of 0.6% and 0.65% respectively.
Imeglimin has shown a favorable safety profile with a low risk of hypoglycemia and no significant weight gain. This can be beneficial for elderly patients and those with kidney impairment.
Taking Imeglimin and Important Considerations
Imeglimin is typically administered as an oral tablet, usually taken twice daily. A common adult dosage is 500 mg of imeglimin hydrochloride, taken in the morning and evening, often with meals to minimize gastrointestinal effects. The specific dosage and duration of treatment will be determined by a healthcare provider based on individual patient factors.
Patients should be aware of potential side effects. Common side effects include nausea, vomiting, diarrhea, abdominal discomfort, headache, and rash. More serious, though rare, side effects can include decreased vitamin B12 levels, low blood sugar (especially when combined with other medications), and a very low risk of lactic acidosis.
It is contraindicated in patients with hypersensitivity to the drug or its components, severe ketosis, diabetic coma, or pre-coma. Caution is advised for patients with severe kidney or liver impairment, and regular monitoring of kidney function is recommended. Patients should inform their doctor if they experience nausea, vomiting, or fever, as these can lead to dehydration and may require temporary discontinuation of the medication.
Global Availability
Imeglimin, marketed under the brand name TWYMEEG, received its first regulatory approval in Japan in June 2021. Sumitomo Dainippon Pharma launched TWYMEEG in September 2021.
This approval was supported by extensive preclinical and clinical data, including positive results from the pivotal Phase 3 TIMES (Trials of IMeglimin for Efficacy and Safety) program. The TIMES program included three trials that evaluated the efficacy and safety of TWYMEEG in over 1,100 patients in Japan.
In all these trials, TWYMEEG met its primary endpoints and objectives, demonstrating a favorable safety and tolerability profile. Its first-in-class status positions it for potential global expansion. Regulatory discussions and trials are ongoing in other regions like China, Europe, and the U.S..