Metformin
Weight ManagementWellness
In plain English
Metformin is a long-established, FDA-approved diabetes pill that lowers blood sugar mainly by reducing the amount of sugar the liver makes and helping the body respond to insulin. It is weight-neutral to modestly weight-lowering and is often used in metabolic and longevity-focused programs. It is taken by mouth, usually with food. The most common side effects are digestive (nausea, diarrhea); long-term use can lower vitamin B12 levels, which is why B12 is sometimes combined with it.
The science
Metformin is a biguanide that activates AMP-activated protein kinase (AMPK) and reduces hepatic gluconeogenesis, improving insulin sensitivity without stimulating insulin secretion (so it rarely causes hypoglycemia alone). In UKPDS 34, intensive glucose control with metformin in overweight patients with newly diagnosed type 2 diabetes reduced any diabetes-related endpoint by 32%, diabetes-related death by 42%, and all-cause mortality by 36% versus diet alone, with a durable long-term legacy effect. Common adverse effects are gastrointestinal; it can reduce B12 absorption over time; and the rare but serious risk is lactic acidosis, chiefly in renal impairment. Its use for weight and longevity beyond diabetes is an area of active study and is largely off-label.