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Observational Study
. 2024 Apr 11:15:1366940.
doi: 10.3389/fendo.2024.1366940. eCollection 2024.

The maintenance of long-term weight loss after semaglutide withdrawal in obese women with PCOS treated with metformin: a 2-year observational study

Mojca Jensterle  1   2 , Simona Ferjan  1   2 , Andrej Janez  1   2
Affiliations
Observational Study

The maintenance of long-term weight loss after semaglutide withdrawal in obese women with PCOS treated with metformin: a 2-year observational study

Mojca Jensterle et al. Front Endocrinol (Lausanne). .

Abstract

Background: Withdrawal of semaglutide is frequently followed by weight regain due to compensatory biological changes that prevent the maintenance of long-term weight loss. There are some studies implying that metformin might attenuate weight regain. The weight trajectory after discontinuation of short-term semaglutide treatment in obese women with PCOS who continued metformin treatment has not yet been evaluated.

Aims: We explored changes in body weight, cardiometabolic and endocrine parameters in obese women with PCOS who continued treatment with metformin 2 years after discontinuation of short-term intervention with semaglutide.

Methods: 25 women with PCOS and obesity, aged 33.7 ± 5.3 years (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 change, cardiometabolic, and endocrine parameters were assessed 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. Two 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 (p=0.003). At the end of the study, 21 out of 25 subjects had lower body weight compared to baseline. Improvements in cardiometabolic parameters including decrease in total and LDL cholesterol, fasting glucose, and glucose after OGTT that had been seen during semaglutide-treatment phase reverted towards baseline two years after semaglutide cessation. Free testosterone levels significantly decreased during semaglutide treatment from 6.16 (4.07-9.71) to 4.12 (2.98-6.93) nmol/l, (p= 0.012) and did not significantly deteriorate after semaglutide discontinuation.

Conclusion: Two years after semaglutide withdrawal, women with PCOS who continued with metformin regained about one-third of the semaglutide-induced weight loss. At the end of the follow up, 84% of women had a lower body weight than at baseline.

Keywords: PCOS; maintenance; metformin; obesity; semaglutid; weight regain.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The protocol of the study.
Figure 2
Figure 2
Comparison of weight at baseline (timepoint 1) with values at the end of semaglutide intervention (timepoint 2) and at the end of the study (timepoint 3): (A) median (25%-75%) and (B) individual weight trajectories.
Figure 3
Figure 3
Comparison of cardiometabolic parameters at baseline (timepoint 1) with values at the end of semaglutide intervention (timepoint 2) and at the end of the study (timepoint 3): (A) fasting plasma glucose, (B) glucose 0 min OGTT, (C) glucose 120 min OGTT, (D) cholesterol, (E) LDL cholesterol, and (F) HDL cholesterol. Data are presented as median (25%-75%).
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The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The study was supported by Slovenian Research Agency grants #P3-0298, #P3-0343.
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