Studies of metformin outside type 2 diabetes measured different endpoints in different groups, and several randomized studies did not find a significant benefit. The prescribing information for metformin ER tablets states use as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus, and its patient information leaflet says medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Use for the conditions below is off-label.
Polycystic ovary syndrome
A Cochrane systematic review of randomised trials in women with polycystic ovary syndrome (PCOS) undergoing ovulation induction reported that metformin versus placebo or no treatment may improve live birth rates (OR 1.59, 95% CI 1.00 to 2.51, 4 studies, 435 women), with low-quality evidence. The abstract does not give a single metformin dose. The same review concluded that clomiphene citrate remains preferable to metformin for ovulation induction in obese women with PCOS.
A systematic review and meta-analysis of randomized trials in women with PCOS (metformin at any dose and any duration, per the abstract) found that metformin alone compared with lifestyle showed similar BMI at 6 months. A review in Australian Prescriber states that metformin is of benefit for reducing excess body weight and improving hormonal and metabolic outcomes in those with high metabolic risk (e.g. body mass index greater than 25 kg/m2) with PCOS. That is a review's statement, not a trial result, and the excerpt used here gives no size or dose.
Gestational diabetes and antipsychotic-related weight gain
A randomized trial in women with gestational diabetes mellitus compared metformin (with supplemental insulin if required) with insulin. It concluded that metformin is not associated with increased perinatal complications as compared with insulin. The excerpt used here does not state the number of women or the metformin dose, and the comparison was with insulin, not placebo.
A meta-analysis of randomized placebo-controlled trials in people taking antipsychotics (metformin dose varied; subgroup analyses found outcomes influenced by metformin dose) wrote that its results suggest adjunctive metformin is a reasonable choice for antipsychotic-induced weight gain and metabolic abnormalities.
Randomized studies that did not find a benefit
These randomized studies reported no significant benefit on their stated endpoints.
| Study | What the source says |
|---|---|
| MA.32, breast cancer | A randomized trial in breast cancer patients without diabetes assigned 850 mg of oral metformin twice a day (n = 1824) or oral placebo twice a day (n = 1825) for 5 years. Among patients with high-risk operable breast cancer without diabetes, adding metformin versus placebo to standard treatment did not significantly improve invasive disease-free survival. |
| CAMERA, coronary heart disease | A randomized, double-blind, placebo-controlled trial in non-diabetic patients with coronary heart disease gave metformin (850 mg twice daily) or matching placebo. The primary endpoint was progression of mean distal carotid intima-media thickness (cIMT) over 18 months in the modified intention-to-treat population. The authors concluded that metformin had no effect on cIMT and little or no effect on several surrogate markers of cardiovascular disease in non-diabetic patients with high cardiovascular risk, taking statins. |
| Diabetes Prevention Program cancer analysis | A randomized study within the Diabetes Prevention Program concluded that neither assignment to metformin nor intensive lifestyle (ILS) reduced cancer incidence among adults at high risk of diabetes. The program's original design used metformin 850 mg twice daily. After a median follow-up of 21 years, 546 participants (173 metformin, 182 ILS, and 191 placebo) were diagnosed with a first incident cancer. |
What this does not tell you
Each result belongs to its own group and endpoint. Women with PCOS, women with gestational diabetes, people taking antipsychotics, patients with breast cancer, patients with coronary heart disease and adults at high risk of diabetes are different populations, and a result in one does not carry over to another. The label's leaflet says medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet.
Several sources here are reviews or abstracts, and some give hedged results ("may improve," "low-quality evidence"). A study with no significant benefit reports on its stated endpoint only. The gestational diabetes conclusion is a comparison with insulin, not a statement that metformin is without risks. These sources do not cover side effects. A licensed provider decides whether any medicine fits a person's situation.