Endocrine Abstracts

Background: Withdrawal of anti-obesity medication is frequently followed by weight regain due to compensatory biological changes that prevent the maintenance of long-term weight loss. In STEP 1 trial extension participants regained two-thirds of their prior weight loss during the 1-year off-treatment follow-up period after withdrawal of semaglutide 2.4 mg and discontinuation of active lifestyle intervention support. There are some studies implying that metformin might attenuate weight regain after weight loss in women with polycystic ovary syndrome (PCOS). To date, the amount of weight regain after semaglutide withdrawal in obese women with PCOS who continue treatment with metformin has not yet been evaluated.

Aims: We explored changes in body weight, cardiometabolic and endocrine parameters in obese women with PCOS 2 years after semaglutide cessation.

Methods: 25 obese women with PCOS (33.7±5.3 years, body mass index (BMI) 36.1±3.9 kg/m², mean±SD) were treated with once-weekly subcutaneous semaglutide 1.0 mg as an adjunct to metformin 2000 mg/day and lifestyle intervention for 16 weeks. At week 16, semaglutide was discontinued. Treatment with metformin 2000 mg/day and promotion of lifestyle intervention were continued during the 2- year follow up period. weight, cardiometabolic and endocrine parameters were assessed to 2 years after semaglutide discontinuation.

Results: During semaglutide treatment phase, weight decreased from 101 (90-106.8) kg to 92 (83.3-100.8) kg. 2 years after semaglutide withdrawal, weight was 95 (77-104) kg. The net weight loss 2 years after discontinuation of semaglutide remained significant when compared to baseline (-7 (-14.3 to -1.5) kg, P=0.001). Improvements in cardiometabolic parameters including decrease in total and LDL cholesterol, triglycerides and fasting glucose and glucose after OGTT that had seen during semaglutide-treatment phase, reverted towards baseline two years after semaglutide cessation. The reduction in free testosterone from 6.16 (4.07-9.71) to 4.12 (2.98-6.93) pmol/l (P=0.004) and in androstenedione from 6.62 (4.36-8.77) to 5.49 (3.78-6.84) nmol/l, (P=0.002), observed during semaglutide treatment phase remained significant for 2 years (P=0.045 and P=0.023, respectively).

Conclusion: Two years after semaglutide withdrawal, women with PCOS regained one-third of their prior weight loss. Improvements of cardiometabolic variables reverted to baseline, whereas improvement of endocrine parameters achieved during semaglutide treatment phase persisted 2 years after semaglutide cessation. The role of metformin in attenuation of weight regain after semaglutide discontinuation needs to be explored in randomized controlled studies in different insulin resistant populations.