Data from a phase 2 study of women with overweight or obesity and polycystic ovary syndrome suggests use of licogliflozin was associated with significant reductions in hyperinsulinemia and androgenemia in this patient population.
New data from a phase 2 trial suggests licogliflozin, a dual SGLT1/2 inhibitor, could offer potential as a treatment option for polycystic ovary syndrome (PCOS).
While much of the attention paid to dual SGLT1/2 inhibitor agents has been given to sotagliflozin and its cardioprotective effects, results from the phase 2 trial of licogliflozin suggest use of the agent could lead to improvements in hyperinsulinemia and androgenemia in women with PCOS.
“SGLT1/2 inhibition may represent a novel therapeutic option for patients with PCOS. Further studies with longer treatment duration considering milder PCOS phenotypes and clinical outcome parameters such as ovulation rate are warranted to elucidate the full potential of dual SGLT1/2 inhibition in PCOS,” wrote investigators.
With previous data indicating dual inhibition of SGLT1/2 could reduce hyperandrogenemia and hyperinsulinemia, but not trials examining SGLT1/2 inhibition in patients with PCOS, the Novartis Pharmaceuticals-led study was created with a randomized, placebo-controlled, double-blind, multicenter design to assess whether use of licogliflozin would impact androgens in women with PCOS. Conducted between October 4, 2017 and June 4, 2018 at sites in the US and Germany, enrolled 29 women and randomized them in a 1:1 ratio to licogliflozin 50 mg or placebo for 2 weeks.
All patients included in the trial fulfilled Rotterdam criteria for phenotype A or B, were overweight or obese, and were considered insulin resistant. The primary endpoint of the study was the effect on geometric mean of serial free testosterone (FT) samples and parameters of insulin resistance, including total testosterone, androstendione (A4), DHEA, dehydroepiandrosteronsulfate (DHEAS), and SHBG.
Per study protocol, patients received oral doses of 50 mg licogliflozin or matching placebo 3 times per day for 14 days before meals. Study evaluations for safety or efficacy were performed on days 8, 15, and 22 of the trial.
The study population had a mean age of 27.6±5.3 years, a mean bodyweight of 105.2±18.7 kg, and a mean BMI of 38.1±6.3 kg/m2. Overall, 15 were randomized to licogliflozin and 15 were randomized to placebo. Investigators pointed out 9 subjects were excluded from analysis due to evidence of ovulation or missing baseline values, but noted baseline values were similar between the study arms.
Upon analysis, investigates observed no change in concentration of free testosterone based on use of licogliflozin. Licogliflozin was associated with a 19% reduction in A4 (TRLIK066:TRPCB(A4): 0.81; 90% CI, 0.68-0.99; P=.089) and a 24% reduction in DHEAS (TRLIK066:TRPCB(DHEAS): 0.76; 90% CI, 0.65-0.89; P=.008).
Additionally, results suggested hyperinsulinemia was reduced by 70% with use of licogliflozin ([TRLIK066:TRPCB(MAXI): 0.26; 90% CI, 0.20-0.34; P <.001], [TRLIK066:TRPCB(AUCI): 0.32; 90% CI, 0.25-0.41; P < .001]). Safety analyses indicated diarrhea and nausea occurred as common adverse events with use of licogliflozin.
“We present the first placebo-controlled, randomized trial with a dual SGLT1/2i in patients with PCOS showing a licogliflozin-mediated reduction in glucose, insulin as well as A4 and DHEAS concentrations after 2 weeks of treatment,” wrote investigators.
This study, “Licogliflozin versus placebo in women with polycystic ovary syndrome (PCOS): a randomised, double-blind, phase 2 trial,” was published in Diabetes, Obesity, and Metabolism.