Characterization of the influence of vildagliptin on model-assessed -cell function in patients with type 2 diabetes and mild hyperglycemia.

Abstract

OBJECTIVE:

This study was conducted to characterize the effects of vildagliptin on beta-cell function in patients with type 2 diabetes and mild hyperglycemia.

DESIGN:

A 52-wk double-blind, randomized, parallel-group study comparing vildagliptin (50 mg every day) and placebo was conducted in 306 patients with mild hyperglycemia (glycosylated hemoglobin of 6.2-7.5%). Plasma glucose and C-peptide levels were measured during standard meal tests performed at baseline, wk 24 and 52, and after 4-wk washout. Insulin secretory rate (ISR) was calculated by C-peptide deconvolution, and beta-cell function was quantified with a mathematical model that describes ISR as a function of absolute glucose levels (insulin secretory tone and glucose sensitivity), the glucose rate of change (rate sensitivity), and a potentiation factor.

RESULTS:

Vildagliptin significantly increased fasting insulin secretory tone [between-group difference in adjusted mean change from baseline to wk 52 (AM Delta) = +34.1 +/- 9.5 pmol.min(-1).m(-2), P < 0.001] glucose sensitivity (AM Delta = +20.7 +/- 5.2 pmol.min(-1).m(-2).mm(-1), P < 0.001), and rate sensitivity (AM Delta = +163.6 +/- 67.0 pmol.m(-2).mm(-1), P = 0.015), but total insulin secretion (ISR area under the curve at 0-2 h) and the potentiation factor excursion during meals were unchanged. These improvements in beta-cell function were accompanied by a decrease in the glucose area under the curve at 0-2 h (AM Delta = -1.7 +/- 0.5 mm/h, P = 0.002) and in glycosylated hemoglobin (AM Delta = -0.3 +/- 0.1%, P < 0.001). None of the effects of vildagliptin remained after 4-wk washout from study medication.

CONCLUSIONS:

Consistent with previous findings from shorter-term studies in patients with more severe hyperglycemia, in patients with mild hyperglycemia, improved beta-cell function is maintained throughout 52-wk treatment with vildagliptin and underlies a sustained improvement in glycemic control. However, no effects remain after washout.

• Authors: Andrea Mari, Werner A Scherbaum, Peter M Nilsson, Gerard Lalanne, Anja Schweizer, Beth E Dunning, Sophie Jauffret, James E Foley
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 93 Issue 1 Pg. 103-9 (Jan 2008) ISSN: 0021-972X [Print] United States
• PMID: 17925336 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Glycated Hemoglobin A
• Hypoglycemic Agents
• Insulin
• Nitriles
• Pyrrolidines
• C-Reactive Protein
• Vildagliptin
• Adamantane

Topics

• Adamantane (analogs & derivatives, pharmacology, therapeutic use)
• Blood Glucose (metabolism)
• C-Reactive Protein (metabolism)
• Diabetes Mellitus, Type 2 (blood, drug therapy)
• Double-Blind Method
• Female
• Glycated Hemoglobin (metabolism)
• Humans
• Hyperglycemia (blood, drug therapy)
• Hypoglycemic Agents (pharmacology, therapeutic use)
• Insulin (blood)
• Insulin-Secreting Cells (drug effects)
• Male
• Middle Aged
• Models, Biological
• Nitriles (pharmacology, therapeutic use)
• Pyrrolidines (pharmacology, therapeutic use)
• Vildagliptin