Dr. Balas and associates investigated the mechanisms by which vildagliptin reduces postmeal plasma glucose concentrations in type 2 diabetic patients by examining the response to a single dose of vildagliptin in patients not previously exposed to a DPP-4 inhibitor.

Vildagliptin completely suppressed plasma DPP-4 activity for more than 14 hours, during which meal-stimulated plasma insulin and C-peptide concentrations increased significantly and plasma glucagon decreased significantly, the authors report.
These changes produced significant reductions in postmeal plasma glucose concentration throughout the overnight period, the results indicate, and fasting plasma glucose was 14 mg/dL lower than baseline on the morning after evening administration of vildagliptin. Insulin secretion increased within 30 minutes after ingestion of vildagliptin and remained elevated after the meal and throughout the sleeping hours, the researchers note.

Within 60 minutes after vildagliptin administration and for all time periods in the ensuing 12 hours, suppression of endogenous glucose production was significantly greater than after placebo administration, the report indicates.

“Due to the fact they might preserve beta cell function (and number), one should think of starting DPP-4 inhibitor or an incretin-mimetic as soon as type 2 diabetes is diagnosed." "I think DPP-4 inhibitors will soon find their place as first and second-choice therapy," Dr. Balas said.

Dr. Balas explained that, because DPP-4 inhibitors "don't seem very effective when they are administered as single-therapy, it is likely that their first indication will be as add-on therapy to metformin or a thiazolidinedione." "If the safety profile proves excellent in long-term studies (as it did in short- and medium-term ones), most likely DPP-4 inhibitors will replace sulfonylureas in current practice."

J Clin Endocrinol Metab 2007;92:1249-1255.

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