To observe the efficacy of semaglutide injection combined with letrozole tablet in the treatment of obese polycystic ovary syndrome with insulin resistance (PCOS-IR) patients.

Patients with PCOS-IR were divided into treatment group and control group according to the treatment regimen. The control group was administered oral dydrogesterone tablets (10 mg per dose, twice daily) for 14 days to induce withdrawal bleeding. Starting from the 5th day of withdrawal bleeding, letrozole tablets were given orally at a dose of 2.5 mg per day for 5 consecutive days. Two days after drug withdrawal, transvaginal ultrasound monitoring was performed. When the dominant follicle reached or exceeded 18 mm in diameter, human chorionic gonadotropin for injection (1.0×10⁴ U) was intramuscularly injected to induce ovulation. If ovulation did not occur, the dose of letrozole tablets was increased to 7.5 mg per day in the next menstrual cycle. The treatment group received subcutaneous injections of semaglutide (0.25 mg per dose, once weekly for 4 consecutive weeks; starting from the 5th week, the dose was adjusted to 0.5 mg per dose, once weekly for another 8 consecutive weeks). After a 1-week drug withdrawal period (washout period), the same ovulation induction protocol as that for the control group was adopted. Both groups received treatment for 3 to 6 menstrual cycles, and the medication was discontinued immediately once ovulation or pregnancy was achieved. Clinical efficacy, clinical manifestations, reproductive hormone levels, insulin resistance, inflammatory marker levels, follicular development, and the adverse drug reactions were compared between the two groups.

A total of 93 cases were included, with 48 cases in the control group and 45 cases in the treatment group. After treatment, the total effective rates of the control group and the treatment group were 70.83% (34 cases/48 cases) and 88.89% (40 cases/45 cases), respectively; the Rosenfield acne scores were (1.56±0.62) and (1.29±0.59) points, respectively; the Ferriman-Gallwey hair scores were (13.31±3.25) and (11.89±2.85) points, respectively; the follicle-stimulating hormone was (6.86±1.24) and (7.50±1.13) IU·L^-1, respectively; the levels of luteinizing hormone were (8.18±1.52) and (7.48±1.63) IU·L^-1, respectively; the levels of fasting blood glucose (FPG) levels were (4.86±0.97) and (4.36±0.69) mmol·L^-1, respectively; the fasting insulin (FINS) levels were (9.25±1.96) and (8.41±1.87) μIU·mL^-1, respectively; the insulin resistance indexes were 1.83±0.39 and 1.63±0.27, respectively; the vascular endothelial growth factors were (92.17±10.82) and (87.45±10.36) ng·L^-1, respectively; the levels of interleukin-6 were (6.74±0.93) and (6.32±0.99) pg·mL^-1, respectively; the number of follicles were (8.44±1.35) and (7.93±1.01), respectively; the maximum follicle diameters were (11.68±2.44) and (13.05±2.69) mm, respectively; the above indicators in the treatment group were compared with those in the control group and it showed statistically significant differences (all P< 0.05). The total incidences of adverse drug reactions in the experimental group and the control group were 8.89% (4 cases/45 cases) and 10.42% (5 cases/48 cases) (P>0.05).

Semaglutide injection combined with letrozole tablets has significant efficacy in the treatment of PCOS-IR patients, can effectively improve insulin resistance, and has relatively good safety in non-pregnant or non-lactating women.