Effects of the Dipeptidyl Peptidase-IV Inhibitor Vildagliptin on Incretin Hormones, Islet Function, and Postprandial Glycemia in Subjects With Impaired Glucose Tolerance  

Oleh:

Rosenstock, Julio ; Foley, James E. ; Rendell, Marc ; Landin-Olsson, Mona ; Holst, Jens J. ; Deacon, Carolyn F. ; Rochotte, Erika ; Baron, Michelle A.

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Diabetes Care vol. 31 no. 01 (Jan. 2008), page 30.
Topik: AUC; area under the curve ; DPP-4; dipeptidyl peptidase-IV ; GIP; gastric inhibitory polypeptide ; GLP-1; glucagon-like peptide 1 ; HOMA-IR; homeostasis model assessment of insulin resistance ; IFG; impaired fasting glucose ; IGT; impaired glucose tolerance ; ISI; insulin sensitivity index ; OGTT; oral glucose tolerance test ; PPG; prandial glucose level

Ketersediaan

Perpustakaan FK Nomor Panggil: D05.K.2008.01 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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OBJECTIVE—This study was conducted to determine the effects of vildagliptin on incretin hormone levels, islet function, and postprandial glucose control in subjects with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS—A 12-week, double-blind, randomized, parallel-group study comparing vildagliptin (50 mg q.d.) and placebo was conducted in 179 subjects with IGT (2-h glucose 9.1 mmol/l, A1C 5.9%). Plasma levels of intact glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP), glucose, insulin, C-peptide, and glucagon were measured during standard meal tests performed at baseline and at week 12. Insulin secretory rate (ISR) was estimated by C-peptide deconvolution. The between-group differences (vildagliptin – placebo) in the adjusted mean changes from baseline to end point in the total and incremental () area under the curve (AUC)0–2 h for these analytes were assessed by ANCOVA; glucose AUC0–2 h was the primary outcome variable. RESULTS—Relative to placebo, vildagliptin increased GLP-1 (AUC, +6.0 ± 1.2 pmol · l–1 · h–1, P < 0.001) and GIP (AUC, +46.8 ± 5.4 pmol · l–1 · h–1, P < 0.001) and decreased glucagon (AUC, –3.0 ± 1.0 pmol · l–1 · h–1, P = 0.003). Although postprandial insulin levels were unaffected (AUC, +20.8 ± 35.7 pmol · l–1 · h–1, P = 0.561), prandial glucose excursions were reduced (AUC, –1.0 ± 0.3 mmol · l–1 · h–1, P < 0.001), representing an 30% decrease relative to placebo. ß-Cell function as assessed by the ISR AUC0–2 h/glucose AUC0–2 h was significantly increased (+6.4 ± 2.0 pmol · min–1 · m–2 · mmol · l–1, P = 0.002). Adverse event profiles were similar in the two treatment groups, and no hypoglycemia was reported. CONCLUSIONS—The known effects of vildagliptin on incretin levels and islet function in type 2 diabetes were reproduced in subjects with IGT, with a 32% reduction in postprandial glucose excursions and no evidence of hypoglycemia or weight gain. OBJECTIVE—This study was conducted to determine the effects of vildagliptin on incretin hormone levels, islet function, and postprandial glucose control in subjects with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS—A 12-week, double-blind, randomized, parallel-group study comparing vildagliptin (50 mg q.d.) and placebo was conducted in 179 subjects with IGT (2-h glucose 9.1 mmol/l, A1C 5.9%). Plasma levels of intact glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP), glucose, insulin, C-peptide, and glucagon were measured during standard meal tests performed at baseline and at week 12. Insulin secretory rate (ISR) was estimated by C-peptide deconvolution. The between-group differences (vildagliptin – placebo) in the adjusted mean changes from baseline to end point in the total and incremental () area under the curve (AUC)0–2 h for these analytes were assessed by ANCOVA; glucose AUC0–2 h was the primary outcome variable. RESULTS—Relative to placebo, vildagliptin increased GLP-1 (AUC, +6.0 ± 1.2 pmol · l–1 · h–1, P < 0.001) and GIP (AUC, +46.8 ± 5.4 pmol · l–1 · h–1, P < 0.001) and decreased glucagon (AUC, –3.0 ± 1.0 pmol · l–1 · h–1, P = 0.003). Although postprandial insulin levels were unaffected (AUC, +20.8 ± 35.7 pmol · l–1 · h–1, P = 0.561), prandial glucose excursions were reduced (AUC, –1.0 ± 0.3 mmol · l–1 · h–1, P < 0.001), representing an 30% decrease relative to placebo. ß-Cell function as assessed by the ISR AUC0–2 h/glucose AUC0–2 h was significantly increased (+6.4 ± 2.0 pmol · min–1 · m–2 · mmol · l–1, P = 0.002). Adverse event profiles were similar in the two treatment groups, and no hypoglycemia was reported. CONCLUSIONS—The known effects of vildagliptin on incretin levels and islet function in type 2 diabetes were reproduced in subjects with IGT, with a 32% reduction in postprandial glucose excursions and no evidence of hypoglycemia or weight gain.

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