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Vildagliptin Reduces Glucagon during Hyperglycemia and Sustains Glucagon Counterregulation during Hypoglycemia in Type 1 Diabetes.

Author:
  • Johan Farngren
  • Margaretha Persson
  • Anja Schweizer
  • James E Foley
  • Bo Ahrén
Publishing year: 2012
Language: English
Pages: 3799-3806
Publication/Series: The Journal of clinical endocrinology and metabolism
Volume: 97
Issue: 10
Document type: Journal article
Publisher: The Endocrine Society

Abstract english

Context:

The dipeptidyl peptidase-4 inhibitor, vildagliptin, inhibits glucagon secretion at hyperglycemia but appears to enhance glucagon counterregulation during hypoglycemia in type 2 diabetes.Objective:The objective of the investigation was to study whether vildagliptin also improves α-cell function in type 1 diabetes (T1D).



Patients and Methods:

The study was a single-center, double-blind, randomized, placebo-controlled crossover study involving 28 patients with C-peptide negative and antibody positive T1D [21 males, seven females, glycosylated hemoglobin 57.9 mmol/mol (7.5%)]. Patients received vildagliptin (50 mg twice a day) or placebo as an add-on to their insulin therapy for 4 wk each. On d 28 of the respective treatment period, patients were served a standard meal (500 kcal) to raise the circulating incretin hormone levels followed by a hyperinsulinemic hypoglycemic clamp at 2.5 mmol/liter.



Main Outcome Measure:

The increase in plasma glucagon levels during the 30-min hypoglycemic clamp (min 165-195 of the test) was measured.Results:During the meal, glucagon levels were lower with vildagliptin than with placebo (120 min area under the curve(glucagon) 2.4 ± 0.2 vs. 2.6 ± 0.2 nmol/liter × minutes, P = 0.022 for between group difference). In contrast, during hypoglycemia, the glucagon counterregulation was not reduced by vildagliptin (increase in glucagon 1.5 ± 1.0 pmol/liter with vildagliptin vs. 1.7 ± 0.8 pmol/liter with placebo, P = NS). In addition, the counterregulatory responses in epinephrine, norepinephrine, cortisol, and pancreatic polypeptide were not different between the treatments. During the 4-wk treatment period, vildagliptin reduced the mean glycosylated hemoglobin, whereas there was no change with placebo [between group difference was -3.4 ± 1.0 mmol/mol (-0.32 ± 0.09%; P = 0.002)] from baseline of 57.9 mmol/mol (7.5%).



Conclusions:

Vildagliptin, although inhibiting glucagon secretion during hyperglycemia, does not compromise the glucagon counterregulatory response during hypoglycemia in T1D.

Keywords

  • Endocrinology and Diabetes

Other

Published
  • Internal Medicine - Epidemiology
  • ISSN: 1945-7197
E-mail: johan [dot] farngren [at] med [dot] lu [dot] se

Research project participant

Diabetes

32

Research student

Medicine, Lund

32

Lund University Diabetes Centre, CRC, SUS Malmö, Jan Waldenströms gata 35, House 91:12. SE-214 28 Malmö. Telephone: +46 40 39 10 00