Endocrine Abstracts

Introduction: High conversion rates to impaired glucose tolerance (IGT) and diabetes in PCOS indicate that current treatment strategy with lifestyle modification and metformin is insufficient. Preservation of β-cell function remains unaddressed although it is declined by 80% long before IGT is identified. Alogliptin is selective dipeptidyl peptidase-4 inhibitor improving insulin sensitivity (IS) and β-cell function. Pioglitazone predominantly improves insulin resistance (IR) and when given early also preserve β-cell function. The aim of the study was to evaluate whether the addition of alogliptin alone or in combination with pioglitazone improves β-cell function along with IR as measured by static and dynamic glucose homeostasis models in metformin treated PCOS with persistent high metabolic risk.

Design: In 12-week randomized study, alogliptin (ALO) 25 mg QD (n=15) or alogliptin 25 mg QD and pioglitazone (PIO) 30 mg QD (n=15) was added to metformin (MET) 1000 mg BID in 30 PCOS women (aged 34.4±6.5 years, BMI 39.0±4.9 kg/m², HOMA-IR 4.82±2.52, mean ± S.D.). Fasting and acute glucose and insulin response to 2-h meal tolerance test was determined at baseline and study end. The ability of β-cell function to adapt insulin secretion to ambient IS was assessed by adaptation index (AI).

Results: 14 patients on MET-ALO and 14 on MET-ALO-PIO completed the study. MET-ALO and MET-ALO-PIO resulted in significant decrease of HOMA-IR (for −1.56±2.29 (P=0.039) vs −2.86±3.34 (P=0.001) and increase in IS after meal ingestion (oral glucose IS) for 31.37±97.52 ml min⁻¹ m⁻² (P=0.007) vs 39.0±58.11 (P=0.039), respectively. AI across the entire group was significantly improved from 329.60±200.63 to 442.51±303.87 (P=0.048). Triple combination also led to significant improvement of androgen and lipid profiles.

Conclusion: Alogliptin alone and in particular in combination with pioglitazone improved meal related β-cell function along with IS and IR when added to metformin resistant PCOS.