Add on DPP-4 inhibitor alogliptin alone or in combination with pioglitazone improved β-cell function and insulin sensitivity in metformin treated PCOS.
OBJECTIVE
Impaired β-cell function remains unaddressed in PCOS. The aim of the study was to evaluate whether dipeptidyl peptidase-4 (DPP-4) inhibitor alogliptin (ALO) alone or in combination with pioglitazone (PIO) improves β-cell function along with insulin resistance (IR) in metformin (MET) treated obese women with PCOS with persistent IR.


METHODS
In 12-week randomized study, ALO 25 mg QD (n=15) or ALO 25 mg QD and PIO 30 mg QD (n=15) was added to MET 1000 mg BID in PCOS women (aged 34.4 ± 6.5 years, BMI 39.0 ± 4.9 kg/m2, HOMA-IR 4.82 ± 2.52, mean ± SD). Model derived parameters of glucose homeostasis from the meal tolerance test (MTT) were determined. The ability of the β-cell function was assessed by the adaptation index (AI).


RESULTS
MET-ALO and MET-ALO-PIO resulted in a significant decrease of HOMA-IR (by 1.6±2.3 (p=0.039) and 2.9±3.3 (p=0.001), respectively) and an increase in insulin sensitivity (IS) after meal ingestion (oral glucose IS) by 31.4±97.5 ml·min-1·m-2(p=0.007) vs 39.0±58.1 ml·min-1·m-2(p=0.039), respectively. AI across the entire group was significantly improved from 329.6±200.6 to 442.5±303.9 (p=0.048).


CONCLUSIONS
ALO alone and in combination with PIO improved IR along with dynamic IS and meal related β-cell function when added to MET treated PCOS.
a Department of Endocrinology, Diabetes and Metabolic Diseases , University Medical Centre Ljubljana , Ljubljana , Slovenia.
Mojca
M
Jensterle
b Pharmacogenetics Laboratory, Institute of Biochemistry, Faculty of Medicine , University of Ljubljana , Ljubljana , Slovenia.
Katja
K
Goricar
a Department of Endocrinology, Diabetes and Metabolic Diseases , University Medical Centre Ljubljana , Ljubljana , Slovenia.
Andrej
A
Janez
D000328:Adult; D015992:Body Mass Index; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D062407:Meals; D008687:Metformin / Q000627:therapeutic use; D009765:Obesity / Q000150:complications / Q000503:physiopathology; D000077205:Pioglitazone; D010880:Piperidines / Q000627:therapeutic use*; D011085:Polycystic Ovary Syndrome / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D011236:Prediabetic State / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control; D015995:Prevalence; D017524:Slovenia / Q000453:epidemiology; D045162:Thiazolidinediones / Q000627:therapeutic use*; D014498:Uracil / Q000031:analogs & derivatives* / Q000627:therapeutic use
D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D010880:Piperidines; D045162:Thiazolidinediones; D014498:Uracil; D008687:Metformin; C520853:alogliptin; D000077205:Pioglitazone
Alogliptin; PCOS; insulin resistance; pioglitazone; β-cell function