Imeglimin Hydrochloride
Indications
Imeglimin Hydrochloride is used for:
Type 2 diabetes
Adult Dose
Oral
Tablet
Type 2 diabetes as an adjunct to diet and exercise to improve glycemic control. It should also be approved as an add-on therapy in patients who are taking metformin or a dipeptidyl peptide 4 (DPP-4) inhibitor.
The usual adult dosage is 1000 mg administered orally twice daily in the morning and evening.
No hepatic function-related adverse events were reported in the imeglimin monotherapy group of the longterm monotherapy and combination therapy study.
Child Dose
Renal Dose
Patients with CKD 2 or 3a receiving oral imeglimin 1000 mg twice daily were found to have exposure comparable to that in the reference group, indicating no necessity of dose adjustment for these patients.
The dosage of imeglimin should be reduced to 500 mg twice daily in patients with CKD 3b or 4.
No clinical studies of imeglimin in patients with CKD 5 (eGFR <15 mL/min/1.73 m2) have been conducted
Administration
Contra Indications
Hypersensitivity
Precautions
pregnant or breastfeeding women
children
patients with pituitary dysfunction or adrenal dysfunction
patients with malnutrition, starvation, irregular dietary intake, lack of dietary intake or weakness
patients regularly taking intense muscle exercise
patients prone to excessive alcohol intake
patients with renal or liver dysfunction (especially patients with eGFR less than 45 mL/min/1.73 m2 and patients on dialysis).
lactic acidosis in combination of Metformin.
Pregnancy-Lactation
Interactions
Adverse Effects
Side effects of Imeglimin Hydrochloride :
Gastrointestinal disorders, Constipation, Hypoglycemia.
Mechanism of Action
Possible benefits of these mechanisms to improve glucose homeostasis include increasing insulin sensitivity, decreasing gluconeogenesis, increasing β-cell function, increasing mitochondrial function, and decreasing oxidative stress. Imeglimin has several documented effects on mitochondrial function. It has been found to enhance generation of adenosine triphosphate (ATP) and increase the ATP/adenosine diphosphate ratio, resulting in improvement of mitochondrial function.
In addition, imeglimin amplifies glucose-stimulated insulin secretion. It improves β-cell function by increasing nicotinamide phosphoribosyltransferase, which leads to increased nictotinamide adenine dinucleotide and ultimately contributes to calcium mobilization in the insulin secretion amplification pathway.
Enhanced insulin effects can be seen in both the liver and skeletal muscle. Recently, imeglimin was found to prevent endothelial cell death in human cells by inhibiting the opening of the mitochondrial permeability transition pore without inhibiting mitochondrial respiration.