The effect of DPP-4 inhibition with sitagliptin on incretin secretion and on fasting and postprandial glucose turnover in subjects with impaired fasting glucose

Research output: Contribution to journalJournal articleResearchpeer-review

Gerlies Bock, Chiara Dalla Man, Francesco Micheletto, Rita Basu, Paula D Giesler Rn, Jeanette Laugen, Carolyn F Deacon, Jens J Holst, Gianna Toffolo, Claudio Cobelli, Robert A Rizza, Adrian Vella

Abstract Objective: Low Glucagon-like Peptide-1 (GLP-1) concentrations have been observed in impaired fasting glucose (IFG). It is uncertain if these abnormalities contribute directly to the pathogenesis of IFG and impaired glucose tolerance. Dipeptidyl peptidase-4 (DPP-4) inhibitors raise incretin hormone concentrations enabling an examination of their effects on glucose turnover in IFG. Research Design and Methods: We studied 22 subjects with IFG using a double blind, placebo-controlled parallel group design. At the time of enrollment, subjects ate a standardized meal labeled with [1-(13)C]-glucose. Infused [6-(3)H] glucose enabled measurement of systemic meal appearance (MRa). Infused [6,6-(2)H(2)] glucose enabled measurement of endogenous glucose production (EGP) and glucose disappearance (Rd). Subsequently, subjects were randomized to100mg of sitagliptin daily or placebo. After an 8-week treatment period, the mixed meal was repeated. Results: As expected, subjects with IFG who received placebo did not experience any change in glucose concentrations. Despite raising intact GLP-1 concentrations, treatment with sitagliptin did not alter either fasting or postprandial glucose, insulin or C-peptide concentrations. Postprandial EGP (18.1+/-0.7 vs. 17.6+/-0.8 mumol/kg/min, p = 0.53), Rd (55.6+/-4.3 vs. 58.9+/-3.3 mumol/kg/min, p = 0.47) and MRa (6639+/-377 vs. 6581+/-316 mumol/kg per 6h, p = 0.85) were unchanged. Sitagliptin was associated with decreased total GLP-1 implying decreased incretin secretion. Conclusions: DPP-4 inhibition did not alter fasting or postprandial glucose turnover in people with IFG. Low incretin concentrations are unlikely to be involved in the pathogenesis of IFG.
Original languageEnglish
JournalClinical Endocrinology
Volume73
Pages (from-to)189-196
ISSN0300-0664
DOIs
Publication statusPublished - 2010

ID: 18699346