Clinical comparison · PCOS & fertility · Updated 2026-07-02
Metformin is an insulin sensitizer; clomiphene is a SERM used to induce ovulation. This table reproduces labeled and trial-reported facts verbatim, per cell. The two address different mechanisms, so their outcomes are not directly comparable. The page reports facts only and does not recommend a choice.
Every value below is reproduced verbatim from an FDA prescribing-information document or a published clinical trial, and each cell links to its source. This page does not rank the two options, does not declare one safer or more effective, and is not medical advice.
| Dimension | Metformin | Clomiphene |
|---|---|---|
| Drug class | Biguanide (insulin sensitizer)[1] | Selective estrogen receptor modulator (SERM)[2] |
| Primary PCOS role | Insulin resistance and metabolic support[3] | Ovulation induction[2] |
| Reported outcome | Improves ovulation and pregnancy rates vs placebo (Cochrane)[3] | 19.1% live-birth rate in PPCOS II[4] |
| Most common side effect | Diarrhea 53.2% (monotherapy)[1] | Vasomotor flushes 10.4%[2] |
| Distinct labeled caution | Lactic acidosis (rare); hold around iodinated contrast[1] | Visual disturbances (~1.5%) warrant discontinuation[2] |
| Pregnancy handling | Sometimes continued under specialist care (historical category B)[1] | Contraindicated once pregnant; confirm before each cycle[2] |
Different targets, not comparable
The Cochrane metformin review measured ovulation and pregnancy rates for a metabolic drug; the PPCOS II clomiphene live-birth figure is for an ovulation-induction drug. Because they act by different mechanisms, the numbers are not a head-to-head. PPCOS II (NEJM 2014)
Clomiphene is used to induce ovulation; metformin primarily targets insulin resistance and metabolic factors (FDA Clomid label; Cochrane).
The FDA Clomid label notes visual disturbances (about 1.5%) that warrant discontinuation, and it is contraindicated once pregnancy occurs.
Editorial reviews from ClearHormones of telehealth providers in this category. These are not treatment recommendations, and prescribing decisions rest with a licensed clinician.