Endocrine Abstracts

Objective: Metformin is the first-line therapy for PCOS with high metabolic risk, yet a large proportion of patients cannot tolerate it due to associated gastrointestinal adverse events. The alternative pharmacological strategy when metformin cannot be tolerated is not well established in this population. Our aim was to evaluate whether sitagliptin (SITA) preserves metabolic profile in metformin (MET) intolerant PCOS with high metabolic risk.

Design and methods: A 12-week prospective randomized open-label study was conducted with 30 obese MET intolerant women with PCOS (aged 35.0±7,2 years, BMI 36,9±5.5 kg/m²). They were randomized to lifestyle intervention and SITA 100mg QD or lifestyle intervention alone as controls (CON). All participants underwent standard anthropometric, endocrine measurements and OGTT. Model derived indexes of insulin resistance (IR) and β-cell function were calculated.

Results: SITA improved beta cell function as assessed by HOMA beta for 45,9±35,8 (P=0,001), modified beta cell function index (MBCI=I0XG0/(G120+G60-7)) for 7,9±7 (P=0,002) and QUICKI for −0,03±0,03 (P=0,002) and increased IR as assessed by HOMA-IR and insulin action index (IAI=1/G0XI0) for 1,8±1,7 (P=0,002) and −0,01±0,01(P=0,003). By contrast, beta cell function decreased in CON arm. The between group differences were significant for HOMA-beta (P=0,000), MBCI (P=0,010) and QUICKI (P=0,025). The conversion rate from normal glucose tolerance to impaired glucose tolerance (IGT) or T2DM was prevented in SITA (3/15 of subjects with MTG before and after the study). In CON 4 women had IGT at the beginning. After 12 weeks IGT was observed in 2 and T2DM in 3 subjects.

Conclusion: SITA improved beta cell function and prevented a conversion rate to IGT and T2DM in metformin intolerant PCOS with high metabolic risk when compared to lifestyle alone.