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Vildagliptin improved islet function in patients with type 2 diabetes
There may be additional mechanisms of action for DPP-IV inhibitors beyond enhancing postprandial incretin effects.
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Vildagliptin improved islet function in patients with type 2 diabetes under fasting conditions, suggesting DPP may have metabolic benefits in addition to enhancing meal-induced glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide.
The researchers conducted a double blind trial to examine the effects of DPP-IV inhibition on fasting islet function in patients with type 2 diabetes. Patients were treated with diet or metformin for at least six months and had HbA1c levels of 6.5% to 7.5%.
For three months, the researchers randomly assigned 41 patients to receive 50 mg of vildagliptin (Galvus, Novartis) twice a day or placebo followed by a two-week washout period. Measurements of insulin secretion in response to intravenous glucose and arginine before and after treatment and after drug washout were taken.
Improvements observed
There were improvements in HbA1c levels for the vildagliptin group (6.7% to 6.3%; P<.001) and the placebo group (6.5% to 6.3%; P<.001).
“Vildagliptin increased fasting GLP-1 levels in patients taking metformin, but not those managed with diet, and raised active gastric inhibitor peptide levels slightly,” the researchers wrote.
Plasma DPP-IV activity was 8.7% mU/mL x min–1 at baseline and was reduced to 0.35% mU/mL x min–1 in the vildagliptin group (P<.01), according to the study.
Plasma levels of intact GLP-1 were 3.5 pM at baseline and 8.3 pM after12-week treatment with vildagliptin (P<.05). Patients assigned to vildagliptin with metformin had baseline levels of GLP-1 of 2.1 pM (P<.05) and elevated levels of GLP-1 calculated at 11.2 pM at 12 weeks (P<.05).
Treatment with DPP-IV inhibitor demonstrated improvement in acute insulin (50%) and C-peptide responses to glucose (100%; P<.05). The slope of the C-peptide response to glucose was increased by 33% (P=.023).
“Based on the findings, it appears that DPP-IV inhibitors can promote beta-cell function in the presence of low levels of plasma incretins, and this effect seems likely to contribute to the therapeutic response to vildagliptin,” the researchers wrote.
J Clin Endocrinol Metab. 2009;94:81-88.