What are the effects and safety of using Imiglimin for medical treatment?

Imeglimin: A Novel Oral Antidiabetic Agent for Type 2 Diabetes

Imeglimin is an effective and well-tolerated first-in-class oral antidiabetic medication that reduces HbA1c by approximately 1.1-1.2% with a favorable safety profile, including no severe hypoglycemia, making it a viable option for type 2 diabetes management either as monotherapy or in combination therapy. 1, 2, 3

Mechanism of Action

Imeglimin works through a unique dual mechanism that targets mitochondrial dysfunction, a fundamental defect in type 2 diabetes:

• Pancreatic effects: Amplifies glucose-stimulated insulin secretion (GSIS) and preserves β-cell mass through enhanced glucose-stimulated ATP generation and NAD+ synthesis via the salvage pathway 1
• Peripheral effects: Enhances insulin action by inhibiting hepatic glucose output and improving insulin signaling in both liver and skeletal muscle 1
• Mitochondrial correction: Rebalances respiratory chain activity by partially inhibiting Complex I while correcting deficient Complex III activity, reducing reactive oxygen species formation and preventing mitochondrial permeability transition pore opening 1, 4

This mechanism differs fundamentally from biguanides, sulfonylureas, and GLP-1 receptor agonists 1

Clinical Efficacy

Glycemic Control

The most robust real-world evidence comes from the 2025 INDI-TIMES study of 8,301 Indian patients, showing:

• Mean HbA1c reduction of 1.12% over 3 months 3
• Fasting plasma glucose decreased by 29.41 mg/dL 3
• Postprandial glucose decreased by 62.41 mg/dL 3
• 45.35% of patients achieved HbA1c <7% 3

Comparative Effectiveness

Phase IIa trials demonstrated that imeglimin 1000 mg twice daily was as effective as metformin 850 mg twice daily in reducing glucose AUC, fasting plasma glucose, and HbA1c 2

Dosing Recommendations

Standard dosing: Imeglimin 1000 mg twice daily (total daily dose 2000 mg) 5, 2, 3

• Can be used as monotherapy in treatment-naïve patients 3
• Effective as add-on therapy to DPP-4 inhibitors and low-dose metformin 5
• Used in dual therapy combinations in 60% of real-world patients 3

Safety Profile

Favorable Tolerability

Imeglimin exhibits superior tolerability compared to metformin, with key advantages:

• No severe hypoglycemia reported in phase III trials 1
• No adverse events reported in the large INDI-TIMES study of 8,301 patients 3
• More favorable gastrointestinal tolerability profile than metformin 2

Additional Benefits

• Weight reduction of approximately 2 kg over 3 months 3
• Improvements in lipid profile, hepatic function, and blood pressure observed in real-world use 3
• Reduces liver steatosis through increased fatty acid oxidation 4

Clinical Considerations

Patient Selection

Imeglimin is appropriate for:

• Treatment-naïve patients with type 2 diabetes (HbA1c 7-9.9%) 5, 3
• Patients inadequately controlled on DPP-4 inhibitors plus low-dose metformin (500-1000 mg/day) 5
• Patients requiring alternatives to metformin due to gastrointestinal intolerance 2

Monitoring

• Assess HbA1c at baseline and 3-month intervals to evaluate response 5, 3
• Monitor fasting and postprandial glucose levels 2, 3
• Track weight, blood pressure, and lipid parameters as secondary benefits 3

Combination Therapy Strategy

When adding imeglimin to existing therapy with DPP-4 inhibitor plus low-dose metformin, this approach is preferable to metformin dose escalation for patients who cannot tolerate higher metformin doses or prefer avoiding gastrointestinal side effects 5, 2