Exenatide, dapagliflozin, or Phentermine/Topiramate differentially affect metabolic profiles in polycystic ovary syndrome
Open accessAbstract
Context: Glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors reduce weight and improve insulin sensitivity via different mechanisms. Objective: The efficacy of once-weekly exenatide (EQW) and dapagliflozin (DAPA) alone and coadministered (EQW/DAPA), DAPA/extended-release (ER) metformin (DAPA/MET), and phentermine topiramate extended release (PHEN/TPM) on metabolic parameters, body composition, and sex hormones were examined in obese women with PCOS. Methods: Nondiabetic women (n = 119; aged 18-45 years) with a body mass index (BMI) greater than 30 and less than 45 and polycystic ovary syndrome (National Institutes of Health criteria) were randomly assigned in a single-blinded fashion to EQW (2 mg weekly); DAPA (10 mg daily), EQW/DAPA (2 mg weekly/10 mg daily), DAPA (10 mg)/MET (2000 mg XR daily), or PHEN (7.5 mg)/TPM (46 mg ER daily) treatment for 24 weeks. Study visits at baseline and 24 weeks included weight, blood pressure (BP), waist (WC) measures, and body composition evaluated by dual-energy x-ray absorptiometry (DXA). Oral glucose tolerance tests were conducted to assess glycemia and mean blood glucose (MBG), and compute insulin sensitivity (SI) and secretion (IS) measures. Sex steroids, free androgen index (FAI), and lipid profiles were measured in the fasting sample. Results: EQW/DAPA and PHEN/TPM resulted in the most loss of weight and total body fat by DXA, and WC. Despite equivalent reductions in BMI and WC with PHEN/TPM, only EQW/DAPA and EQW resulted in significant improvements in MBG, SI, and IS. Reductions in fasting glucose, testosterone, FAI, and BP were seen with all drugs. Conclusion: Dual therapy with EQW/DAPA was superior to either alone, DAPA/MET and PHEN/TPM in terms of clinical and metabolic benefits in this patient population.
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Only one small trial has evaluated phentermine/topiramate ER in a PCOS population, comparing phentermine 7.5 mg plus topiramate 46 mg ER daily to exenatide 2 mg once weekly (n=36 for both arms).
“Only one small trial has evaluated this combination in a PCOS population, comparing phentermine 7.5 mg plus topiramate 46 mg ER daily to exenatide 2 mg OW (n = 36 for both arms) [171].”
From Precision obesity medicine: A phenotype-guided framework for pharmacologic therapy across the lifespan (2025) · cites this paper as [171]
The Trial Design section confirms that women with PCOS received phentermine 7.5 mg/topiramate 46 mg ER daily or exenatide 2 mg weekly, among five treatment arms. Table 1 lists 20 exenatide and 16 phentermine/topiramate participants who completed the trial—36 across the two arms, not 36 in each. The paper describes its trial as a first comparison but cannot establish the broader claim that it was the only trial. (LLM, conf=0.92)
Experimental — accuracy not yet measuredAfter 24 weeks, mean weight loss with phentermine/topiramate ER in PCOS obese women was 8%, higher than the 6.6% weight loss reported at 56 weeks in the general population.
“After 24 weeks, mean weight loss with phentermine/topiramate ER in PCOS obese women was 8%, even higher than the 6.6% Weight loss reported at 56 weeks in the general population [171]”
From Precision obesity medicine: A phenotype-guided framework for pharmacologic therapy across the lifespan (2025) · cites this paper as [171]
The Participants and Weight Trajectories sections describe a 24-week trial in obese women with PCOS and report weight loss with phentermine/topiramate ER. The table in Additional information reports a 9.0 kg mean weight reduction for that group, but the copy does not state an 8% mean loss or the claimed 6.6% loss at 56 weeks in the general population; searches for both percentages and 56 weeks did not establish that comparison. Page numbers were not available in the indexed passages. (LLM, conf=0.84)
Experimental — accuracy not yet measuredIn nondiabetic women with BMI ≥30 and ≤45 kg/m2 and polycystic ovary syndrome, once-weekly EX-LAR or dapagliflozin or co-administration for 24 weeks all led to weight loss, with most weight loss in double treatment.
“Hirsch et al. (117) found that after 24 weeks of drug treatment of once-weekly EX-LAR or dapagliflozin or co-administered, nondiabetic women with a BMI (≥30 kg/m2 and ≤ 45 kg/m2) and polycystic ovary syndrome all lost weight. Among them, weight loss was the most in the double treatment.”
From GLP−1 receptor agonists for the treatment of obesity: Role as a promising approach (2023) · cites this paper as [117]
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- Authors
- Elkind-Hirsch, K. E., Chappell, N., Seidemann, E., Storment, J., & Bellanger, D.
- Affiliations
- Woman's Hospital (US)
- Corresponding author
- Elkind-Hirsch, Karen E
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2021-06-07
- Volume
- 106
- Issue
- 10
- Pages
- 3019-3033
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W3168202556
- Cited by
- 96
- References
- 38
- Citations by year
- 2026: 16 · 2025: 21 · 2024: 24 · 2023: 19 · 2022: 15 · 2021: 1
- FWCI
- 12.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- AstraZeneca
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Keywords
- polycystic ovary syndrome, exenatide, dapagliflozin, phentermine/topiramate, metformin, obesity, weight loss, insulin sensitivity, insulin secretion, glycemic control, sex hormones, free androgen index, body composition, blood pressure, lipid profile, combination therapy
- MeSH terms
- Topiramate, Exenatide, Adolescent, Adult, Benzhydryl Compounds, Blood Glucose, Drug Therapy, Combination, Female, Glucose Tolerance Test, Glucosides, Humans, Hypoglycemic Agents, Metformin, Middle Aged, Obesity, Phentermine, Polycystic Ovary Syndrome, Prospective Studies, Weight Loss, Single-Blind Method, Treatment Outcome, Young Adult
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