Effects of sitagliptin on glycemia, incretin hormones, and antropyloroduodenal motility in response to intraduodenal glucose infusion in healthy lean and obese humans, and patients with type 2 diabetes treated with or without metformin

  1. Christopher K Rayner1,2
  1. 1Discipline of Medicine, University of Adelaide, Adelaide, South Australia, 5000
  2. 2Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide
  3. 3Department of Biomedical Science, University of Copenhagen, Copenhagen, Denmark.
  1. Corresponding author: Christopher K Rayner Email: chris.rayner{at}adelaide.edu.au

Abstract

The impact of variations in gastric emptying, which influence the magnitude of GIP and GLP-1 secretion, on glucose-lowering by DPP-4 inhibitors is unclear. We evaluated responses to intraduodenal glucose infusion (60g over 120min, ie. 2kcal/min – a rate that predominantly stimulates GIP, but not GLP-1) after sitagliptin vs. control in 12 healthy lean and 12 obese subjects, and in 12 type 2 patients taking metformin 850mg bd vs. placebo. As expected, sitagliptin augmented plasma intact GIP substantially, and intact GLP-1 modestly. Sitagliptin attenuated glycemic excursions in healthy lean and obese, but not type 2 subjects, without affecting glucagon or energy intake. In contrast, metformin reduced fasting and glucose-stimulated glycemia, suppressed energy intake, and augmented total and intact GLP-1, total GIP and glucagon in type 2 subjects, with no additional glucose-lowering when combined with sitagliptin. These observations indicate that in type 2 diabetes (i) the capacity of endogenous GIP to lower blood glucose is impaired, (ii) the effect of DPP-4 inhibition on glycemia is likely to be dependent on adequate endogenous GLP-1 release, requiring gastric emptying above 2kcal/min, and (iii) the action of metformin to lower blood glucose is not predominantly via the incretin-axis.

  • Received October 21, 2013.
  • Accepted March 11, 2014.

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  1. Diabetes
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