Vildagliptin (Galvus) Suppresses Postprandial Blood Glucose

A single dose augmented insulin secretion and inhibited glucagon release. This single dose of vildagliptin had carryover throughout the evening and sleeping hours until the following morning. A recent study has found that a single dose of the DPP-IV inhibitor vildagliptin caused a significant suppression of endogenous glucose production in patients with type 2 diabetes.

Previous research has indicated that the therapeutic effects of DPP-IV inhibitors are related mostly to their effect on glucagon-like peptide 1 and glucose-dependent insulinotropic peptide, and how this in turn effects insulin secretion. “However, there are a number of observations that suggest that factors other than change in insulin levels may be important,” said Ralph A. DeFronzo, MD, chief of the diabetes division at the University of Texas Health Science Center at San Antonio. “We also know that the effects of these drugs can be seen in the absence of a meal. Clearly there is a lot more that we need to learn about how these drugs work.”

DeFronzo and colleagues conducted a study testing the effects of an acute single dose of vildagliptin (Novartis) given before an evening meal in patients with type 2 diabetes. Research on chronic administration of the drug has shown that glucose levels drop over time, but the present study looked for acute effects independent of these chronic metabolic changes.

The study included 16 patients (mean age 48; 10 men) with type 2 diabetes, an average BMI of 34.4 and an average HbA1c of 9%. On two days separated by about two weeks, each patient received either 100 mg vildagliptin or placebo, followed 30 minutes later by a six-hour meal tolerance test.

“When the patients ingested vildagliptin, you could see within 15 minutes a marked inhibition of DPP-IV activity,” DeFronzo said. “This was at a maximum within 30 minutes and the inhibition persisted until 8 a.m. the following morning.”

Following vildagliptin, patients’ GLP-1 levels nearly doubled, an effect that also persisted until 8 a.m. the following morning. A similar effect was seen with GIP levels.

Also seen throughout the night was a glucose difference of about 15 mg/dL between vildagliptin and placebo patients. “Clearly this single dose of vildagliptin had carryover throughout the evening and sleeping hours until the following morning,” DeFronzo said.

Researchers also saw a significantly greater suppression of endogenous glucose production during the meal tolerance test with vildagliptin compared with placebo (1.02 mg/kg·min vs. 0.74 mg/kg·min; P=.004); this difference was also evident from 6 p.m. through 8 a.m. the following morning (0.8 mg/kg·min vs. 0.5 mg/kg·min; P<.03).

Insulin secretory rates also increased by 21% during the meal tolerance test with vildagliptin (P=.003 vs. placebo). This occurred despite a reduction in mean plasma glucose with vildagliptin compared with placebo (213 mg/dL vs. 230 mg/dL; P=.006).
Finally, suppression of mean plasma glucagon during the meal tolerance test was five times greater with vildagliptin than with placebo (P<.02).

By including 3-3H-glucose and 1-14C-glucose intravenously along with the meal, the researchers were able to examine glucose appearance rates. “We failed to see any effect of vildagliptin on the rate of oral glucose appearance from the gastrointestinal tract,” DeFronzo said. “This means that there is not a delay in gastric emptying and there is no enhancement of glucose uptake by the gastrointestinal tract or the liver.”

DeFronzo said that this study shows that a single dose of vildagliptin results in a “nice improvement in beta-cell function tested in the insulin secretory rate, and nice reduction in endogenous glucose production.”

Dr. DeFronzo is on the advisory board for and has received a research grant from Novartis. Baig M, Balas B, Watson C, et al. Vildagliptin suppresses endogenous glucose production and increases beta cell function after single dose administration in type 2 diabetic patients. Presented at: 42nd European Association for the Study of Diabetes Annual Meeting 2006; Sept. 14-17; Copenhagen.

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DID YOU KNOW:
Diet or Exercise: Which One Works Better to Reduce Your Risk of Diabetes? According to a new study by researchers examining whether a calorie-restrictive diet can extend the human lifespan, both diet and exercise provide profound benefits to reduce the risk of diabetes. The researchers, who initially thought that exercise would produce greater benefits, examined 50 to 60 year olds whose body mass index was between 23 and 30 (at the high end of normal weight or overweight, but not obese). The study participants were divided into groups and treated with either an exercise regimen or a calorie-restricted diet. All participants had their insulin action and glucose tolerance evaluated at the beginning and end of the study. The ultimate goal of the diet group was to cut the number of calories they ate by 20 percent, while the exercise group was charged with burning 20 percent more of their calories. Glucose tolerance and insulin levels improved to roughly the same degree in both the dieters and exercisers. Both groups also lost weight. American Journal of Clinical Nutrition November 2006; 84(5): 1033-1042

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