Licogliflozin versus placebo in women with polycystic ovary syndrome: A randomized, double‐blind, phase 2 trial
Susanne Tan, Stanislav Ignatenko, Frank Wagner, Anuja Dokras, Jochen Seufert, Denise Zwanziger, Karin Dunschen, Marjorie Zakaria, Neda Huseinovic, Craig T. Basson, Ping Mahling, Dagmar Führer, Markus Hinder
Abstract
Abstract Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism and insulin resistance. The dual sodium‐glucose co‐transporter 1/2 inhibitor (SGLT1/2i) licogliflozin (LIK066) ameliorates hyperinsulinism in patients with diabetes and obesity. This study examines the effect of licogliflozin on androgens in women with PCOS. In a multicentre, randomized, placebo‐controlled, double‐blind, 2‐week trial, patients with PCOS received licogliflozin 50 mg or placebo three times a day (TID). Changes in free testosterone (FT), other androgens and variables of insulin resistance were analysed. Concentration of FT did not change (TR LIK066 :TR PCB [FT]: 0.88; 90% CI: 0.70‐1.11; P = .353). Licogliflozin reduced androstendione (A4) by 19% (TR LIK066 :TR PCB [A4]: 0.81; 90% CI: 0.68‐0.99; P = .089) and dehydroepiandrosteron sulphate (DHEAS) by 24% (TR LIK066 :TR PCB [DHEAS]: 0.76; 90% CI: 0.65‐0.89; P = .008). Hyperinsulinaemia was reduced by 70% by licogliflozin (highest insulin concentration [MAXI]; TR LIK066 :TR PCB [MAXI]: 0·26; 90% CI:0.20‐0.34; P < .001 and area under the curve insulin [AUCI]; TR LIK066 :TR PCB [AUCI]: 0.32; 90% CI: 0.25‐0.41; P < .001). Diarrhoea and nausea occurred as common adverse events. Dual inhibition of SGLT1/2 ameliorates hyperinsulinaemia and hyperandrogenaemia in women with PCOS. Licogliflozin may represent a promising novel treatment option for PCOS.