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The effect of DPP‐4 inhibition with sitagliptin on incretin secretion and on fasting and postprandial glucose turnover in subjects with impaired fasting glucose
Author(s) -
Bock Gerlies,
Man Chiara Dalla,
Micheletto Francesco,
Basu Rita,
Giesler Paula D.,
Laugen Jeanette,
Deacon Carolyn F.,
Holst Jens J.,
Toffolo Gianna,
Cobelli Claudio,
Rizza Robert A.,
Vella Adrian
Publication year - 2010
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.2009.03764.x
Subject(s) - sitagliptin , postprandial , medicine , endocrinology , incretin , glucagon like peptide 1 , dipeptidyl peptidase 4 , impaired fasting glucose , sitagliptin phosphate , placebo , insulin , impaired glucose tolerance , gastric inhibitory polypeptide , type 2 diabetes , glucagon , blood sugar regulation , diabetes mellitus , alternative medicine , pathology
Summary Objective Low glucagon‐like peptide‐1 (GLP‐1) concentrations have been observed in impaired fasting glucose (IFG). It is uncertain whether 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‐blinded, placebo‐controlled, parallel‐group design. At the time of enrolment, subjects ate a standardized meal labelled 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 to 100 mg 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 μmol/kg per min, P = 0·53), Rd (55·6 ± 4·3 vs 58·9 ± 3·3 μmol/kg per min, P = 0·47) and MRa (6639 ± 377 vs 6581 ± 316 μmol/kg per 6 h, 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.