Imeglimin

Structure: First drug in the glimin class, a small tetrahydrotriazine molecule that shares a chemical fragment with metformin but is not a biguanide. It partially inhibits mitochondrial Complex I much more weakly than metformin, and in rodent pancreatic islets raised NAD+ via the NAMPT salvage pathway, amplifying insulin release when glucose is high.

Regulatory status:

• Approved in Japan (Twymeeg, 2021) and India (generics such as Imeglyn, from late 2022)
• Not approved by the FDA, EMA or TGA. Outside Japan and India it is a personal import of an unregistered medicine

Dosage (diabetes label, not a lifter protocol):

• Japan label: 1000mg 2x/day
• Reduced kidney function (eGFR 15-45): 500mg 2x/day in Japanese studies

Key Notes:

• Every human trial is in people with type 2 diabetes. There is no data in healthy or trained people
• Head-to-head vs metformin: similar HbA1c drop to low-dose metformin, and 0.21% better than a metformin dose increase in the MEGMI trial, where 7 of 33 people stopped for GI side effects
• Stacking with metformin raised GI side effects to 38-41% in Japanese studies (vs 11% without metformin in one retrospective study)
• Lower lactic acidosis risk than metformin has only been shown in animals
• No human training study exists. Mouse data suggests it protects muscle in obesity, ageing and fatty liver disease, unlike metformin, which blunted hypertrophy in older adults
• HbA1c may read high for about two months after starting (longer red cell lifespan). Use fructosamine for early checks
• Cleared unchanged by the kidneys: get cystatin C before starting, since creatinine-based eGFR is unreliable in muscular people
• Monitor: fasting glucose, fasting insulin, HOMA-IR, fructosamine, HbA1c, cystatin C, creatinine, ALT/AST

The full evidence review against metformin: Is imeglimin better than metformin for lifters?