Effect of chenodeoxycholic acid sequestrant colesevelam on glucagon-like peptide-1 secretion

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The nasogastric tube was used to avoid the foul taste of chenodeoxycholic acid affecting the study outcome. All dispersions were mixed for 30min at room temperature to allow equal distribution, and for CDCA to bind to colesevelamon day 3. Eachdispersionwas instilled in the stomach for about 1min and the feeding tube was then removed. All participants were studied on four separate experimental days separated by at least 48h. On all 4days, the participants were studied in a recumbent position after a 10h overnight fast including liquids, medication and tobacco use. Participants with type 2 diabeteswere instructed not to take theirmetformin one week before each experimental day in order to exclude confounding effects of metformin treatment.
In randomized order, the participants received: (1)chenodeoxycholic acid 1.25 g, (2) colesevelam 3.75 g (six tablets Cholestagel®), (3) chenodeoxycholic acid 1.25 g+colesevelam 3.75 g, or (4) placebo. All treatments were dispersed in 100 ml water admixed with 1.5 g paracetamol (for evaluation of gastric emptying). The CDCA dose of 1.25 g was chosen because this is the approved dose for dissolving gallstones, and the colesevelamdose of 3.75 g was chosen because this is the approved dose for treatment of hypercholesterolaemia.
Glucose ratio was increased in both groups after chenodeoxycholic acid versus after CDCA+colesevelam (p<0.05), and after chenodeoxycholic acid versus after placebo in the healthy control group (p<0.01). Basal concentrations of insulin and C-peptide were higher in the type 2 diabetes group compared with the healthy control group (107±24 vs. 68±13 pmol/l and 850±114 vs. 552±79 pmol/l). In both groups, there were no significant differences in insulin and C-peptide concentrations, respectively, between the days. After CDCA, glucagon concentrations increasedinboththe type 2 diabetes and the control group, resulting in higher AUCs compared with colesevelam, CDCA+colesevelam and placebo, respectively. Compared with placebo, colesevelam and CDCA+colesevelam did not affect plasma glucagon concentrations. With the most pronounced increments after CDCA, colesevelam and CDCA+colesevelam.