Among women with polycystic ovary syndrome and obesity, those assigned empagliflozin therapy for 12 weeks lost more weight and lowered their metabolic rate compared to those assigned metformin, according to findings from an open-label comparator study.
In an analysis of 39 women with PCOS with a BMI of at least 25 kg/m², researchers also found that empagliflozin therapy was not associated with changes in hormonal or metabolic parameters when compared with metformin, and that women assigned to metformin experienced modest weight gain.
“Empagliflozin, an SGLT2 inhibitor, is a new treatment option for adults with type 2 diabetes; however, its effects in PCOS have not been previously explored,” Zeeshan Javed, MBBS, MD, a clinical research fellow in the department of academic diabetes, endocrinology and metabolism at Hull York Medical School at the University of Hull, United Kingdom, and colleagues wrote in the study background. “Its principal action involves inhibition of glucose reabsorption by the kidney and, therefore, glucose excretion via urine. Notably, this action mechanism is insulin independent; as such it does not increase the risk of hypoglycemia, making it attractive for use in normoglycemic individuals.”
In a randomized, open-label study, researchers analyzed data from women with PCOS assigned to 25 mg empagliflozin (Jardiance, Boehringer Ingelheim; n = 19; mean age, 26 years; mean BMI, 37.1 kg/m²) or 1,500 mg metformin daily (n = 20; mean age, 32 years; mean BMI, 38.7 kg/m²) for 12 weeks. All participants were advised to maintain their normal dietary and lifestyle habits during the study. Across three visits, researchers measured weight, BMI, waist circumference, hip circumference, body composition and endothelial function, as well as reproductive hormones and cardiometabolic parameters, including fasting glucose and lipid profile. Main outcomes were changes in anthropometric and body composition, as well as hormonal and metabolic parameters.
Compared with participants in the metformin group, researchers observed greater percentage changes from baseline for participants in the empagliflozin group for body weight (mean, 1.2% vs. –1.4%; P = .006); BMI (mean, 1.1% vs. –1.4%; P = .006), waist circumference (mean, 0.2% vs. –1.6%; P = .029) and hip circumference (mean, 1.1% vs. –2%; P = .001). Researchers observed similar between-group differences between the metformin and empagliflozin groups for basal metabolic rate (mean, 0.1% vs. –1.8%; P = .024) and fat mass (mean, 3.2% vs. –0.7%; P = .023).
Women in the empagliflozin group also experienced increases in levels of sex hormone-binding globulin (P = .049) and estradiol (P = .032) at 12 weeks; however, researchers observed no other hormonal changes for either group. Similarly, there were no changes observed for either treatment arm at 12 weeks for blood pressure, endothelial function, insulin sensitivity or lipid profile, according to researchers.
In the empagliflozin group, two participants reported adverse events, including headache and dizziness and mild rash, both unrelated to the study drug. There were no serious adverse events in either group.
“Placebo-controlled and comparative treatment [randomized controlled trials] of longer-term duration are needed to confirm these findings and provide further insights into the effects of empagliflozin on PCOS-related outcomes in women with PCOS with different PCOS phenotypes and PCOS-related complications before empagliflozin gains a therapeutic place in PCOS,” the researchers wrote. “Lifestyle interventions should still be considered first line of treatment for overweight/obese women with PCOS for reductions in body weight, central obesity and insulin resistance.” – by Regina Schaffer
Disclosures: The authors report no relevant financial disclosures.