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Short-term sitagliptin therapy preserves beta-cell function in women with PCOS, obesity
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Among women with polycystic ovary syndrome and obesity participating in a lifestyle intervention, those who were assigned the DPP-IV inhibitor sitagliptin were less likely to progress to impaired glucose tolerance and type 2 diabetes than those assigned placebo, study data show.
“Only a few studies have addressed preservation of beta-cell function as a potential target in PCOS,” Mojca Jensterle, MD, PhD, of the department of endocrinology, diabetes and metabolic disease at the University Medical Centre Ljubljana in Slovenia, told Endocrine Today. “It was demonstrated that DPP-IV inhibition can halt or reverse the loss of functional beta-cell mass in animal models and may delay transition to type 2 diabetes. DPP-IV inhibition as an alternative therapeutic option had been proposed yet untested in metformin-intolerant women with PCOS. The present study is the first investigation into the potential role of DPP-IV inhibitors in metformin-intolerant obese POCS.”
Jensterle and colleagues evaluated women (mean age, 35 years) with PCOS and obesity (mean BMI, 36.9 kg/m2) who were metformin-intolerant and randomly assigned to a lifestyle intervention plus 100 mg daily sitagliptin (Januvia, Merck; n = 15) or lifestyle intervention alone (n = 13) for 12 weeks. Researchers sought to determine whether sitagliptin plus lifestyle intervention preserves beta-cell function.
The lifestyle intervention included individual counseling and a reduced-calorie diet.
Fasting measures of beta-cell function, including homeostasis model assessment for beta-cell function index (HOMA-B; P = .001), modified beta-cell function index (P = .002) and quantitative insulin sensitivity check index (P = .002), were all improved with sitagliptin, whereas only HOMA-B significantly decreased with the lifestyle intervention alone.
Compared with baseline, after 12 weeks, fasting insulin and C-peptide significantly increased with sitagliptin, whereas the change was not significant with lifestyle alone.
Compared with baseline, after 12 weeks, sitagliptin decreased progression from normal glucose tolerance to IGT or type 2 diabetes and IGT was observed in two participants in the intervention only group and type 2 diabetes was observed in three compared with baseline.
No serious adverse events were reported.
“DPP-IV inhibitors seem to be a promising alternative in PCOS women with high metabolic risk that have failed with lifestyle intervention and are metformin intolerant,” Jensterle said. “Future larger designs of longer duration should be powered using our preliminary results.” – by Amber Cox
Disclosure
Mojca Jensterle, MD, PhD, can be reached at mojcajensterle@yahoo.com.
Disclosures: The authors report no relevant financial disclosures.
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