Effects of Empagliflozin on Metabolic Parameters in Polycystic Ovary Syndrome

A Randomized Controlled Study

Zeeshan Javed; Maria Papageorgiou; Harshal Deshmukh; Alan S. Rigby; Unaiza Qamar; Jehangir Abbas; Amer Y. Khan; Eric S. Kilpatrick; Stephen L. Atkin; Thozhukat Sathyapalan

Disclosures

Clin Endocrinol. 2019;90(6):805-813. 

In This Article

Abstract and Introduction

Abstract

Background: Empagliflozin is a sodium-glucose-cotransporter-2 inhibitor that improves cardiovascular risk and promotes weight loss in patients with type-2 diabetes. Polycystic ovary syndrome (PCOS) is associated with obesity and increased cardiovascular risk; therefore, empagliflozin may be of benefit for these women. The aim of this study was to compare the effects of empagliflozin vs metformin on anthropometric and body composition, hormonal and metabolic parameters in women with PCOS.

Materials and methods: A randomized open-label study was conducted in women with PCOS who were randomized to either empagliflozin 25 mg (n = 19) or metformin 1500 mg (n = 20) daily for 12 weeks. The main outcomes assessed were changes in anthropometric and body composition, hormonal and metabolic parameters.

Results: Univariate analysis showed significant differences in weight (empagliflozin: −1.4 ± 3.2% vs metformin: 1.2 ± 2.3%; P = 0.006), body mass index (empagliflozin: −1.4 ± 3.2% vs metformin: 1.1 ± 2.2%; P = 0.006), waist circumference (empagliflozin: −1.6 ± 2.8% vs metformin: 0.2 ± 2.1%; P = 0.029) and hip circumference (empagliflozin: −2.0 ± 3.0% vs metformin: 1.1 ± 1.9%; P = 0.001), basal metabolic rate (empagliflozin: −1.8 ± 2.9% vs metformin: 0.1 ± 1.9%, P = 0.024) and fat mass (empagliflozin: −0.7 ± 4.9% vs metformin, 3.2 ± 5.0%; P = 0.023) between the empagliflozin and the metformin groups. These differences were confirmed in linear regression analysis after adjustment for relevant covariates. There were no significant changes in hormonal or metabolic parameters between both groups.

Conclusion: There was a significant improvement in anthropometric parameters and body composition, in overweight and obese women with PCOS after 12 weeks of treatment with empagliflozin compared to metformin, although no changes were seen in hormonal or metabolic parameters.

Introduction

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder featured by hyperandrogenism, menstrual irregularities and polycystic ovaries that affects women of reproductive age.[1] PCOS is also associated with infertility, obesity, metabolic disturbances and increased cardiovascular risk.[1,2]

Accordingly, the treatment of PCOS is commonly symptom-based, while the ideal treatment would address both the reproductive and metabolic abnormalities related to PCOS.[1,3] Hormonal contraceptives alone or combined with anti-androgens have been the cornerstone for managing menstrual disturbances and clinical or biochemical hyperandrogenaemia;[4] however, some hormonal contraceptives may unfavourably affect the lipid profile in PCOS[5] and increase the risk of thrombosis and cardiovascular events in the general population.[6] Glucose lowering agents including metformin and thiazolidinedione have been shown to be effective in managing the metabolic abnormalities (ie, insulin resistance, hyperinsulinaemia, and diabetes mellitus) and chronic anovulation; however, their use has been inconsistently associated with improvements in weight loss and body composition, menstrual irregularity or clinical symptoms of excess androgens.[7,8]

Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, is a new treatment option for adults with type 2 diabetes;[9] however, its effects in PCOS have not been previously explored. 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 hypoglycaemia, making it attractive for use in normoglycaemic individuals.[10,11] Recent trials have demonstrated that treatment with empagliflozin promotes weight loss,[12] exerts positive effects on arterial stiffness, vascular resistance and blood pressure and decreases the relative risk for cardiovascular and all-cause mortality in patients with type 2 diabetes.[10,13] Evidence from preclinical studies suggests that these cardio-protective effects may be due to the reduction in oxidative stress and suppressed markers of inflammation and fibrosis.[14,15] In humans, the cardiovascular benefits may also be mediated by reductions in HbA1c, insulin resistance, plasma volume, weight/fat mass and inflammation.[16,17] Given that these pathological features are also common in PCOS;[1,2] empagliflozin may be of potential benefit for this population.

Therefore, the aim of this study was to explore and compare the effects of empagliflozin vs metformin on anthropometric, body composition, hormonal and metabolic parameters in women with PCOS.

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