PCOS, weight and GLP-1 medicines: what we know and what we do not know yet

PCOS affects roughly one in ten women of reproductive age and is the commonest cause of irregular ovulation. Many of them have insulin resistance: the body produces more insulin for the same effect, and the high insulin level pushes the ovaries to make more androgens. This mechanism stops the dominant follicle maturing and releasing an egg. Insulin resistance also occurs in women of normal weight, so PCOS is never simply a matter of weight; but when extra weight is present, it reinforces the circle.

That also explains why a moderate change makes a measurable difference. Losing about 5–10 per cent of body weight, roughly 4–8 kilograms for most women, is associated with falling insulin and androgen levels and with the return of ovulatory cycles in a substantial proportion of patients. Reaching an “ideal” weight is not the requirement; a change you can sustain is. Balanced eating, regular movement, sleep and stress management remain the base that the international guideline puts in first place.

The international evidence-based guideline for PCOS, updated in 2023, recommends lifestyle as the first step for all women with PCOS and extra weight, supported properly rather than simply advised. When pregnancy does not follow, letrozole is the first-line treatment for ovulation induction; it outperforms clomifene both for ovulation rates and for live births. Clomifene, gonadotrophins, laparoscopic ovarian drilling and IVF follow according to the individual situation, age and the couple's other factors.

Metformin has a clear but limited place: it improves metabolic measures and may help cycle regularity, particularly where insulin resistance is marked. Its benefit for live birth in IVF cycles remains uncertain, and the guidelines do not recommend it as a standard fertility treatment. This is worth knowing, because metformin is often seen as “the PCOS drug” while its role is supportive.

GLP-1 receptor agonists such as semaglutide, liraglutide and tirzepatide were developed for type 2 diabetes and then for obesity. They slow stomach emptying and reduce appetite, and the weight loss they produce is greater than is usually achieved by diet alone. Reports of unexpected pregnancies in women taking them have two plausible explanations, which may act together: weight loss restores ovulation in women who had not ovulated for years, and slower stomach emptying can reduce the absorption of oral contraceptives, making them less reliable.

This is an observed side effect, not an indication. None of these medicines is approved for treating infertility and none has been studied as a fertility treatment in PCOS. If you are using a GLP-1 medicine and do not want to conceive now, speak to your doctor about contraception that does not depend on absorption from the stomach. If you do want to conceive, that conversation belongs before you start, not after.

The safety of GLP-1 agonists in pregnancy is unknown; human data are sparse and animal studies have raised questions. The semaglutide label therefore advises stopping at least 2 months before you begin trying to conceive, so that the medicine clears from the body; for other molecules the interval differs and is set by your doctor. If you become pregnant while on treatment, do not panic and do not continue the medicine: call the team following you within the first days.

There is a practical reason too. Weight returns in a large proportion of people after stopping, and a rapid regain exactly when you are planning a pregnancy helps neither ovulation nor the course of the pregnancy. These medicines therefore make sense only within a complete plan, with medical follow-up, dietary support and a clear calendar for when they stop and what follows. They are not a short cut to fertility, and they are not bought without a prescription.