Review finds thin evidence on semaglutide and other weight drugs in PCOS

A systematic review published February 14, 2024 in the journal Obesity Reviews found that published evidence on anti-obesity medications in women with polycystic ovary syndrome (PCOS) is "very limited." The review was commissioned to inform the anti-obesity medication section of the 2023 International Evidence-based Guideline for the Assessment and Management of PCOS ^[1][2].

The authors searched Medline, EMBASE, PsycInfo and CINAHL for studies from the previous 10 years, with the search closing in July 2022. They included 11 trials, with 545 participants in intervention arms and 451 in control arms, covering 12 comparisons ^[1].

In descriptive analyses, most agents improved anthropometric outcomes, which include measures such as body weight and waist circumference. Liraglutide, semaglutide and orlistat appeared superior to placebo for those outcomes ^[1].

Pooling results in a meta-analysis was possible for only two comparisons. The first was exenatide versus metformin. Among anthropometric, biochemical hyperandrogenism and metabolic outcomes, the only difference identified was lower fasting blood glucose with metformin than with exenatide (mean difference 0.10 mmol/L, confidence interval 0.02–0.17, I² = 18%, 2 trials) ^[1].

The second pooled comparison was orlistat plus a combined oral contraceptive pill versus the pill alone, which did not improve metabolic outcomes (fasting insulin mean difference −8.65 pmol/L, confidence interval −33.55 to 16.26, I² = 67%, 2 trials) ^[1]. The review states that orlistat plus the pill did not improve metabolic outcomes compared with the pill alone, and that no differences were identified between exenatide and metformin for biochemical hyperandrogenism or metabolic outcomes other than fasting glucose ^[1]. Neither pooled comparison showed a benefit on androgen outcomes ^[1].

Tirzepatide does not appear among the agents in the included trials, and a search that closed in July 2022 would not have captured data on it ^[1].

"Published data examining the effects of anti-obesity agents in women with PCOS are very limited," the authors wrote. "The role of these agents in PCOS should be a high priority for future research." ^[1]

Why it matters for patients

PCOS is a common metabolic and reproductive condition affecting women of reproductive age, and the 2023 guideline is endorsed by 40 societies internationally ^[1]. The section of that guideline covering anti-obesity drugs, however, rests on a small PCOS-specific evidence base ^[1].

The review set out to evaluate hormonal, reproductive, metabolic and psychological outcomes, but could pool results for only two drug comparisons ^[1]. That means questions about how these medications affect androgens, metabolic markers, fertility-related outcomes or psychological symptoms in women with PCOS are not answered by pooled data in this review ^[1].

For semaglutide, the review's descriptive finding was about anthropometric outcomes, such as weight, rather than about PCOS-specific hormonal or metabolic results ^[1]. Much of what clinicians draw on when discussing these drugs with patients who have PCOS comes from studies in other populations, because the PCOS trials are few and small ^[1]. The review does not say whether the drugs change long-term outcomes such as diabetes risk or pregnancy complications in this group; that has not been established by this analysis ^[1].

What happens next

The authors list research into anti-obesity agents in PCOS as a high priority ^[1]. No date for an updated evidence search, or for PCOS-specific guidance covering newer agents such as tirzepatide, has been disclosed ^[1]. The 2023 guideline recommendations were published in Human Reproduction ^[2].