Exenatide, dapagliflozin or phentermine/topiramate different
Glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors reduce weight and improve insulin sensitivity via different mechanisms.

The efficacy of once-weekly exenatide (EQW) and dapagliflozin (DAPA) alone and co-administered (EQW/DAPA), DAPA/extended release 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.

Non-diabetic women (n=119; 18-45y) with BMI 30-45 and PCOS (NIH criteria) were randomized in a single-blind fashion to EQW (2 mg weekly); DAPA (10 mg daily), EQW/DAPA (2 mg weekly/10 mg daily), DAPA (10 mg)/MET (2000mg XR daily) or PHEN (7.5 mg)/TPM (46mg 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 (OGTT) were done to assess glycemia, 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.

EQW/DAPA and PHEN/TPM resulted in the most loss of weight, 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.

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.

Source: https://academic.oup.com/jcem/advance-article-abstract/doi/10.1210/clinem/dgab408/6294193?redirectedFrom=fulltext