Short-Term Combined Treatment With Tirzepatide and Metformin for Overweight/Obese Chinese Women With Polycystic Ovary Syndrome: A Prospective, Open-Label, Randomised Controlled Trial.

AIMS: This study aimed to assess the effects of low-dose tirzepatide combined with metformin (COM) versus metformin (MET) monotherapy in overweight/obese women with polycystic ovary syndrome (PCOS). MATERIALS AND METHODS: Sixty overweight/obese women with PCOS were randomised to the MET group (1000 mg twice daily [BID]) or the COM group (MET: 1000 mg BID, tirzepatide: 5 mg once weekly [QW]) for 16 weeks. The primary outcome was the change in body weight. Secondary outcomes included changes in anthropometric measures other than body weight, body composition, reproductive hormone levels, metabolic and endocrine parameters, inflammatory markers and menstrual cycle regularity. All outcomes were assessed at baseline and week 16. After week 16, participants were switched to MET monotherapy. Barrier contraception was required for 8 weeks and pregnancy outcomes were subsequently evaluated between weeks 25 and 48. RESULTS: After 16 weeks of treatment, compared with the MET group, the COM group resulted in greater reductions in weight (-1.7 ± 2.5 kg vs. -10.4 ± 3.5 kg; p < 0.001), body mass index (BMI) (-0.68 ± 1.82 vs. -4.12 ± 1.37 kg/m; p < 0.001), visceral adipose tissue (VAT) (-4.67 ± 9.59 vs. -34.13 ± 15.33 cm; p < 0.001) and reproductive endocrine-metabolic parameters. Menstrual cycle recovery and total pregnancy rate were higher in the COM group than in the MET group (p = 0.013 and p = 0.014, respectively). CONCLUSIONS: In overweight/obese women with PCOS, low-dose tirzepatide combined with MET was associated with greater reductions in body weight and visceral fat, along with improvements in metabolic and reproductive outcomes compared with MET monotherapy. TRIAL REGISTRATION: ChiCTR2400090908; chictr.org.cn.