Best Weight-Loss Medications for PCOS: 5 Options Ranked by Evidence

For women with PCOS, GLP-1 medications such as semaglutide and tirzepatide are the most effective weight-loss drugs, and they also lower insulin resistance, which drives many PCOS symptoms. A 2025 meta-analysis of randomized trials in women with PCOS found GLP-1 drugs cut weight, waist size and insulin resistance more than metformin or placebo (Lin 2025, Scientific Reports). Metformin is a cheaper, gentler add-on with smaller weight effects, and orlistat is an older option.

How we chose

We ranked each option on four things, checked on September 30, 2026:

• Weight loss in randomized trials of women with PCOS, not only general obesity trials.
• Effects on PCOS itself, such as insulin resistance, androgen levels (the hormones behind acne and unwanted hair) and cycle regularity.
• Guideline support from the 2023 International Evidence-based PCOS Guideline, the main global guideline.
• Fit with pregnancy plans, since many women with PCOS are trying to conceive.

The guideline team notes that most PCOS evidence is still low to moderate quality, and that weight-loss medicine in PCOS is an under-studied area (Teede 2023, PCOS Guideline). A systematic review done for that guideline found liraglutide, semaglutide and orlistat looked better than placebo for weight, but data were limited (Goldberg 2024, Obesity Reviews).

1. Tirzepatide (Zepbound)

Tirzepatide is a weekly shot that copies two gut hormones (GLP-1 and GIP) to cut appetite and improve how your body handles sugar. It produces the largest average weight loss in general obesity trials, about 21% at the top dose (SURMOUNT-1, NEJM 2022).

PCOS-specific data are early. In a 16-week randomized trial of 60 women with PCOS in China, adding low-dose tirzepatide to metformin cut about 10 kg versus 1.7 kg on metformin alone, shrank belly fat, and improved cycle regularity and pregnancy rates (Tirzepatide plus metformin PCOS trial, 2026). That trial was open-label, meaning everyone knew what they were taking.

Best for: women with PCOS who want the most weight loss and are not trying to get pregnant right now.

Trade-offs: nausea and other stomach effects, especially as the dose rises. The label says it may make birth control pills less reliable, so women on the pill should add a barrier method or switch to a non-pill option for four weeks after starting and after each dose increase (MotherToBaby tirzepatide fact sheet).

2. Semaglutide (Wegovy)

Semaglutide copies GLP-1 alone and comes as a weekly shot or a daily pill. In general obesity trials, the shot produced about 15% average weight loss (STEP 1, NEJM 2021).

In women with PCOS, the GLP-1 drug class lowered weight, waist size and insulin resistance in pooled trials (Lin 2025, Scientific Reports). Our tirzepatide vs semaglutide breakdown compares the two head to head.

Best for: women who want a well-studied GLP-1 with a pill option.

Trade-offs: nausea and vomiting were more common than with placebo in the PCOS trials (Lin 2025, Scientific Reports). The Wegovy label says to stop at least two months before a planned pregnancy (Wegovy label, DailyMed). See our guide to planning pregnancy around a GLP-1.

3. Liraglutide (Saxenda and generics)

Liraglutide is an older daily GLP-1 shot, now available as a generic, which can lower the price.

In a 32-week double-blind trial of 82 women with obesity and PCOS, liraglutide 3 mg cut 5.7% of body weight versus 1.4% on placebo, and lowered the free androgen index, a measure of the hormones behind acne and excess hair (Elkind-Hirsch 2022, Fertility and Sterility).

Best for: women who want a GLP-1 at lower cost and can manage a daily shot.

Trade-offs: much less weight loss than weekly semaglutide or tirzepatide, and 58% had stomach side effects in that trial.

4. Metformin

Metformin is a cheap, decades-old diabetes pill that improves insulin sensitivity. It is widely prescribed for PCOS.

A meta-analysis done for the 2023 guideline found metformin plus lifestyle changes lowered BMI, insulin resistance and fasting glucose more than placebo, with more mild stomach upset. The authors called it an effective add-on to lifestyle changes, especially at higher BMI (Melin 2023, European Journal of Endocrinology). The average weight effect is small, about half a BMI point.

Best for: women who want a low-cost first step, or to pair with a GLP-1.

Trade-offs: modest weight loss. Stomach upset is common at first.

5. Orlistat

Orlistat blocks some fat from being absorbed in your gut. It is available by prescription and, at a lower dose, over the counter.

In a meta-analysis of eight studies, adding orlistat to birth control pills in women with PCOS and overweight lowered BMI and waist size and improved hormone levels compared with the pill alone (Orlistat plus contraceptive meta-analysis, 2022).

Best for: women who cannot take a GLP-1 and want a non-injectable option.

Trade-offs: the guideline review found orlistat plus the pill did not improve metabolic measures over the pill alone (Goldberg 2024, Obesity Reviews), and the label lists oily spotting, gas with discharge and urgent bowel movements among the most common side effects (Xenical label, FDA).

Comparison at a glance

How to choose

If weight is your main goal and pregnancy is not on the near horizon, a weekly GLP-1 gives the biggest change and helps insulin resistance too. If you are trying to conceive soon, plan the timing with your prescriber, since GLP-1s are stopped before pregnancy. Metformin is a reasonable start or add-on at low cost. If you are in perimenopause as well, our guide to GLP-1 results in perimenopause covers what changes.

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