Effects of anagliptin on plasma glucagon levels and gastric emptying in patients with type 2 diabetes: An exploratory randomized controlled trial versus metformin

Abstract

Glucagon has an important role in glucose homeostasis. Recently, a new plasma glucagon assay based on liquid chromatography-high resolution mass spectrometry was developed. We evaluated the influence of a dipeptidyl peptidase-4 inhibitor (anagliptin) on plasma glucagon levels in Japanese patients with type 2 diabetes by using this new assay. Methods: Twenty-four patients with type 2 diabetes were enrolled in a prospective, singlecenter, randomized, open-label study and were randomly allocated to 4 weeks of treatment with metformin (1000 mg/day) or anagliptin (200 mg/day). A liquid test meal labeled with sodium [ 13 C] acetate was ingested before and after the treatment period. Samples of blood and expired air were collected over 3 h. Plasma levels of glucose, glucagon, C-peptide, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) were measured, and gastric emptying was also evaluated. Results: Twenty-two patients completed the study (metformin group: n = 10; anagliptin group: n = 12). Glycemic control showed similar improvement in both groups. In the anagliptin group, there was a slight decrease of the incremental area under the plasma concentration versus time curve for glucagon after the test meal (P = 0.048). In addition, the plasma level of active GLP-1 and GIP was increased, and plasma C-peptide was also increased versus baseline. Neither anagliptin nor metformin delayed gastric emptying. Conclusions: In patients with type 2 diabetes maintained endogenous insulin secretion, anagliptin increased the plasma level of active GLP-1 and GIP in association with a slight stimulation of insulin secretion and slight inhibition of glucagon secretion, but did not delay gastric emptying.

Role of anagliptin, a dipeptidyl peptidase-4 inhibitor, in managing type 2 diabetes: A systematic review and meta-analysis

“…[10][11][12][13][14][15][16][17][18][19] Six studies were excluded because they either had no control group, [20][21][22][23] were retrospective cohort studies, [24] or were short-duration (duration 4 weeks) studies. [25]…”

Effect of dipeptidyl peptidase-4 inhibitors on postprandial glucagon level in patients with type 2 diabetes mellitus: A systemic review and meta-analysis

“…The follow-up durations varied from 5–657 days. Circulating glucagon levels were measured by radioimmunoassay ( 23 , 24 , 28 , 29 , 43 , 48 – 51 , 53 , 54 ), enzyme-linked immunosorbent assay (ELISA) ( 55 ), or liquid chromatography-high resolution mass spectrometry ( 52 ) in a MTT/OGTT setting. A detailed risk of bias assessment of the included RCTs can also be found in Table 2 .…”

Glucose‐lowering action through targeting islet dysfunction in type 2 diabetes: Focus on dipeptidyl peptidase‐4 inhibition

“…This was first shown in humans for vildagliptin after a mixed meal in individuals with type 2 diabetes 40 , and was later confirmed for other DPP-4 inhibitors in white patients 3,41 . In Japanese patients, glucagon levels were slightly suppressed by DPP-4 inhibition after meal ingestion in two studies 42,43 , but not significantly changed in another study 44 , whereas in Chinese patients, a clear reduction in glucagon levels after meal ingestion was observed for DPP-4 inhibition 45 . These results might suggest that the increase in insulin secretion is more important than the reduction in glucagon in some populations, although this needs to be tested in further comparative studies.…”