Common name in Nepal: Glycomet, Glucophage, Obimet, Metride
What Is Metformin?
Metformin is a biguanide and is the first-choice oral medication for type 2 diabetes worldwide, recommended as the starting drug for almost all newly diagnosed patients unless there is a specific reason to avoid it. It has been in clinical use since the late 1950s and remains a cornerstone therapy because it is effective, inexpensive, does not cause weight gain, and carries essentially no risk of hypoglycemia on its own.
Mechanism of Action
Metformin's main effect is on the liver, where it suppresses excess glucose production (gluconeogenesis) — a major driver of high fasting blood sugar in type 2 diabetes. It does this largely by activating an intracellular energy-sensing enzyme called AMPK, which in turn switches off the liver's glucose-manufacturing machinery and reduces fat synthesis. Metformin also increases glucose uptake into muscle and modestly reduces glucose absorption in the intestine, partly by altering the gut microbiome. Because it works by reducing glucose output and improving the body's sensitivity to its own insulin — rather than by forcing the pancreas to release more insulin — metformin does not cause hypoglycemia when used alone.
Benefits
Metformin lowers HbA1c by roughly 1 to 1.5 percentage points, is weight-neutral or associated with mild weight loss, and has a long track record of cardiovascular safety, with some evidence suggesting cardiovascular benefit. It is inexpensive and available worldwide, including in Nepal.
Side Effects
Gastrointestinal effects are the most common issue — nausea, diarrhea, abdominal discomfort, bloating, and a metallic taste, especially when starting or increasing the dose. These usually improve over days to weeks and can be minimized by starting at a low dose, increasing slowly, and taking the tablet with food; extended-release formulations are often better tolerated.
Vitamin B12 deficiency can develop gradually over months to years of use, because metformin reduces B12 absorption in the gut. This is often overlooked because its symptoms (fatigue, numbness/tingling in the hands or feet, memory problems) can be mistaken for diabetic neuropathy or simply "getting older." Periodic B12 checking is recommended, particularly for long-term users.
Lactic acidosis is a rare but serious risk — a dangerous buildup of lactic acid in the blood. It is strongly linked to situations where metformin accumulates in the body, particularly significant kidney impairment, liver disease, heavy alcohol use, dehydration, serious infection, or shortly after receiving iodinated contrast dye for a CT scan. In people with normal kidney function, this risk is very low — comparable to the background rate seen in diabetes generally.
Weight change — unlike sulfonylureas or insulin, metformin does not promote weight gain and is often associated with modest weight loss, which is one of the reasons it is preferred as the first-line agent, especially in patients who are overweight.
Precautions
Metformin should be temporarily stopped before procedures using injected iodinated contrast dye (and restarted only after kidney function is confirmed stable), and generally paused during serious acute illness, major surgery, or significant dehydration. Dose reduction or avoidance is needed as kidney function declines: most guidance recommends avoiding metformin once eGFR falls below 30 mL/min, using caution and lower doses between 30–45 mL/min, and monitoring more closely below 60 mL/min. It is not recommended in significant liver disease or in people who drink alcohol heavily. People should be counseled to stay well hydrated and to seek urgent care for unusual muscle pain, difficulty breathing, severe abdominal pain, or extreme tiredness, which can be early warning signs of lactic acidosis.
Required Tests: Before and After Starting
Before starting, kidney function (creatinine/eGFR) should be checked, since this determines whether metformin is appropriate and at what dose. Liver function is also often checked at baseline. During treatment, kidney function should be rechecked every 6 to 12 months (more often if kidney function is borderline or declining), and vitamin B12 levels are generally recommended annually or every 2–3 years, especially for people on long-term therapy or those with symptoms of numbness, tingling, or unexplained fatigue. HbA1c is typically checked every 3 to 6 months to track glucose control.
Sources
Foretz M, Guigas B, Viollet B. "Metformin: update on mechanisms of action and repurposing potential." Nature Reviews Endocrinology, 2023.
Rena G, Hardie DG, Pearson ER. "The mechanisms of action of metformin." Diabetologia, 2017;60(9):1577-1585. DOI: 10.1007/s00125-017-4342-z
U.S. FDA prescribing information for metformin hydrochloride tablets, accessdata.fda.gov
Lazarus B, et al. "Association of Metformin Use With Risk of Lactic Acidosis Across the Range of Kidney Function." JAMA Internal Medicine, 2018.
Aroda VR, et al. "Long-term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study." Journal of Clinical Endocrinology & Metabolism, 2016.