Short-term therapy with combination dipeptidyl peptidase-4 inhibitor saxagliptin/metformin extended release (XR) is superior to saxagliptin or metformin XR monotherapy in prediabetic women with polycystic ovary syndrome: a single-blind, randomized, pilot study

Abstract

Objective: To evaluate efficacy with the dipeptidyl peptidase-4 inhibitor saxagliptin (SAXA), metformin extended release (MET), and combination (SAXA-MET) in patients with polycystic ovary syndrome (PCOS) and impaired glucose regulation.

Design: Prospective, randomized, single-blind drug study.

Setting: Outpatient clinic.

Patient(s): Patients (n = 38) with PCOS (aged 18-42 years) and prediabetic hyperglycemia determined by a 75-gram oral glucose tolerance test.

Intervention(s): Patients were randomized to SAXA-MET (5 mg/2,000 mg), SAXA (5 mg), or MET (2,000 mg) for 16 weeks.

Main outcome measure(s): Fasting and mean blood glucose, insulin sensitivity, insulin secretion, and insulin secretion-sensitivity index (IS-SI) by oral glucose tolerance tests. Free androgen index and lipid levels, average menstrual interval, and anthropometric measurements (body mass index, waist circumference, and waist/height ratio).

Result(s): The study was completed by 34 patients. Nineteen patients had normal glucose tolerance: 3 of 12 (25%) on MET; 6 of 11 (55%) on SAXA; and 10 of 11 (91%) on SAXA-MET (SAXA-MET statistically superior to MET) at study completion. Body mass index, waist circumference, waist/height ratio, free androgen index, insulin sensitivity, IS-SI, and menses improved in all groups; however, IS-SI and menstrual regularity were significantly better with SAXA-MET vs. MET treatment. Triglyceride, triglyceride/high-density lipoprotein cholesterol ratio and mean blood glucose significantly declined in the SAXA-MET and SAXA groups only.

Conclusion(s): This pilot work provides the first evidence regarding the effects of a dipeptidyl peptidase-4 inhibitor alone and in combination with MET in this patient population. Treatment with SAXA-MET was superior to either drug alone in terms of clinical and metabolic benefits in prediabetic patients with PCOS.

Clinical trial registration number: NCT02022007.

Keywords: Dipeptidyl peptidase-4 inhibitor; polycystic ovary syndrome; prediabetic hyperglycemia; saxagliptin.