Metformin
Metformin is a biguanide oral antidiabetic and first-line drug for type 2 diabetes. It lowers hepatic glucose output and improves insulin sensitivity without causing hypoglycaemia on its own. Bodybuilders use it as a glucose-disposal and nutrient-partitioning agent, and it is studied for longevity and body-composition effects.
01 Overview
Metformin reduces hepatic gluconeogenesis primarily through AMPK activation and inhibition of mitochondrial complex I, and modestly improves peripheral insulin sensitivity. It has an exceptional long-term safety record and decades of clinical trials.
In physique use it is taken to blunt fat gain on high-carbohydrate or high-calorie phases and to improve carbohydrate tolerance. It does not itself cause hypoglycaemia unless combined with insulin or secretagogues, but gastrointestinal side effects are common and rare lactic acidosis is the serious risk to watch.
02 Mechanism
Activates hepatic AMPK and inhibits mitochondrial complex I, suppressing gluconeogenesis; also improves insulin-stimulated glucose uptake and alters gut glucose handling and the microbiome.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Body-composition (off-label) | 500–1500 mg/day | Oral | Often split with carbohydrate meals |
| Diabetes | 500–2000 mg/day | Oral | Titrate up with meals to limit GI effects; max ~2550 mg/day |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Improved insulin sensitivityEnhances glucose disposal and reduces hepatic glucose output. | Lower fasting glucose and insulin | Clinical | |
| Modest fat-gain suppressionHelps limit fat accrual and appetite in some users. | Slight weight/fat reduction | Clinical |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Gastrointestinal intoleranceDiarrhoea, nausea, cramping and flatulence, especially on initiation. | Mild | Very common | Clinical | |
| Vitamin B12 depletionReduced B12 absorption with chronic use. | Mild | Common long-term | Clinical | |
| Lactic acidosisA rare but serious buildup of lactate, mostly in renal impairment, dehydration or alcohol excess. | Life-threatening | Rare | Clinical |