What should I expect when starting metformin?
Written and medically reviewed by Zahraa Sater, M.D., M.P.H.
Reviewed August 12, 2026 · Next review due August 12, 2028
Short answer
Most people starting metformin get gastrointestinal side effects in the first weeks. In the FDA label, diarrhea occurred in 53.2 percent and nausea or vomiting in 25.5 percent of people taking immediate release metformin. Starting low, taking it with food and using the extended release form reduce this. Metformin alone does not cause hypoglycemia.
Get urgent care if: you are taking metformin and develop symptoms that can signal lactic acidosis.
- Unusual muscle pain, deep tiredness or weakness that is new
- Trouble breathing or unusually fast breathing
- Stomach pain with nausea or vomiting, especially with diarrhea and dehydration
- Feeling cold, dizzy or lightheaded, or a slow or irregular heartbeat
Stop metformin and seek emergency care if these occur, particularly during a dehydrating illness or after a scan with iodinated contrast.
Metformin lowers glucose mainly by reducing the amount produced by the liver and improving insulin sensitivity in muscle. It has been in use since the 1950s, it is inexpensive, and it does not cause low blood sugar when used on its own. The first two to four weeks are the hard part, and almost all of the difficulty is digestive.
The side effects that actually happen
In the controlled trials in the FDA label for immediate release metformin, diarrhea occurred in 53.2 percent of participants, nausea or vomiting in 25.5 percent, flatulence in 12.1 percent and indigestion in 7.1 percent. With the extended release form the reported figures were much lower, 9.6 percent for diarrhea and 6.5 percent for nausea or vomiting. Symptoms usually settle. If they do not settle within a few weeks, the dose or the formulation is wrong, not the patient.
How to start it so you stay on it
Take metformin with food, start at one low dose daily, and increase every one to two weeks rather than jumping to the target dose. The maximum recommended adult dose is 2,550 mg daily for immediate release and 2,000 mg daily for extended release. If immediate release causes persistent diarrhea, ask to switch to extended release taken with the evening meal. Alcohol amplifies the risk of lactic acidosis and should be limited.
| Issue | What the label says | Practical response |
|---|---|---|
| Diarrhea and nausea | Common, mostly early | Take with food, titrate slowly, consider extended release |
| Vitamin B12 | Fell to subnormal levels in about 7 percent in trials | Check B12 periodically, especially with anemia or neuropathy |
| Kidney function | Contraindicated below eGFR 30 mL/min/1.73 m2 | Check eGFR before starting and at least yearly |
| Lactic acidosis | Boxed warning, rare but can be fatal | Stop and seek care with the symptoms below |
Who should not take it
Metformin is contraindicated in severe renal impairment, defined in the label as an eGFR below 30 mL/min/1.73 m2, and starting it is not recommended when eGFR is between 30 and 45. It should be held before iodinated contrast imaging in people with reduced kidney function, and during acute illness with dehydration, vomiting or sepsis. Long term use lowers vitamin B12 in a minority, so B12 is worth checking periodically, particularly with anemia or numbness in the feet.
Before you start, make sure a recent eGFR and a baseline B12 are on file, agree a titration schedule in writing, and plan to recheck A1C in about three months. If the gastrointestinal effects are still limiting after four weeks at a steady dose, that is a reason to change the plan rather than to abandon metformin.
The clinical detail
The FDA label carries a boxed warning stating that postmarketing cases of metformin associated lactic acidosis have resulted in death, hypothermia, hypotension and resistant bradyarrhythmias. Risk factors include renal impairment, concomitant use of certain drugs such as carbonic anhydrase inhibitors, age 65 or older, radiological studies with contrast, surgery and other procedures, hypoxic states, excessive alcohol intake and hepatic impairment.
The label describes a decrease to subnormal levels of previously normal serum vitamin B12 in approximately 7 percent of patients in controlled trials. Maximum recommended daily dose is 2,550 mg for immediate release and 2,000 mg for extended release in adults. Metformin does not stimulate insulin secretion, so it does not cause hypoglycemia in monotherapy, though it can contribute when combined with insulin or a sulfonylurea.
Written and medically reviewed by Zahraa Sater, M.D., M.P.H.
Reviewed August 12, 2026 · Next review due August 12, 2028
Sources
- GLUCOPHAGE and GLUCOPHAGE XR (metformin hydrochloride) prescribing information. US Food and Drug Administration
- 3. Prevention or Delay of Diabetes and Associated Comorbidities: Standards of Care in Diabetes 2026. American Diabetes Association. PMID 41358891
- Reduction in the Incidence of Type 2 Diabetes with Lifestyle Intervention or Metformin. New England Journal of Medicine. PMID 11832527
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