Abstract | CONTEXT: OBJECTIVE: The aim of the study was to assess effects of the dipeptidyl peptidase-4 inhibitor vildagliptin on alpha-cell response to hyper- and hypoglycemia. DESIGN: We conducted a single-center, randomized, double-blind, placebo-controlled, two-period crossover study of 28-d treatment, with a 4-wk between-period washout. PATIENTS: INTERVENTION: Participants received vildagliptin (100 mg/d) or placebo as outpatients. PRIMARY OUTCOME MEASURE(S): We measured the following: 1) change in plasma glucagon levels during hypoglycemic (2.5 mm glucose) clamp; and 2) incremental (Delta) glucagon area under the concentration-time curve from time 0 to 60 min (AUC(0-60 min)) during standard meal test. Before the study, it was hypothesized that vildagliptin would suppress glucagon secretion during meal tests and enhance the glucagon response to hypoglycemia. RESULTS: The mean change in glucagon during hypoglycemic clamp was 46.7 +/- 6.9 ng/liter with vildagliptin treatment and 33.9 +/- 6.7 ng/liter with placebo; the between-treatment difference was 12.8 +/- 7.0 ng/liter (P = 0.039), representing a 38% increase with vildagliptin. In contrast, the mean glucagon DeltaAUC(0-60 min) during meal test with vildagliptin was 512 +/- 163 ng/liter x min vs. 861 +/- 130 ng/liter x min with placebo; the between-treatment difference was -349 +/- 158 ng/liter x min (P = 0.019), representing a 41% decrease with vildagliptin. CONCLUSIONS:
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Authors | Bo Ahrén, Anja Schweizer, Sylvie Dejager, Beth E Dunning, Peter M Nilsson, Margaretha Persson, James E Foley |
Journal | The Journal of clinical endocrinology and metabolism
(J Clin Endocrinol Metab)
Vol. 94
Issue 4
Pg. 1236-43
(Apr 2009)
ISSN: 1945-7197 [Electronic] United States |
PMID | 19174497
(Publication Type: Journal Article, Randomized Controlled Trial)
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Chemical References |
- Blood Glucose
- Glycated Hemoglobin A
- Hypoglycemic Agents
- Insulin
- Nitriles
- Pyrrolidines
- Glucagon-Like Peptide 1
- Glucagon
- Vildagliptin
- Adamantane
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Topics |
- Adamantane
(analogs & derivatives, therapeutic use)
- Aged
- Blood Glucose
(metabolism)
- Body Mass Index
- Cross-Over Studies
- Diabetes Mellitus, Type 2
(blood, drug therapy)
- Double-Blind Method
- Female
- Glucagon
(blood)
- Glucagon-Like Peptide 1
(blood)
- Glycated Hemoglobin
(metabolism)
- Humans
- Hyperglycemia
(drug therapy)
- Hypoglycemia
(drug therapy)
- Hypoglycemic Agents
(therapeutic use)
- Insulin
(blood, metabolism)
- Insulin Secretion
- Male
- Middle Aged
- Nitriles
(therapeutic use)
- Pyrrolidines
(therapeutic use)
- Vildagliptin
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