Vildagliptin: A Novel Oral Therapy for Type 2 Diabetes Mellitus
Vildagliptin: A Novel Oral Therapy for Type 2 Diabetes Mellitus
Purpose: The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, and role in therapy of vildagliptin for the treatment of type 2 diabetes mellitus were reviewed.
Summary: Vildagliptin is an agent in a new class of medications called dipeptidyl peptidase IV (DPP4) inhibitors. By inhibiting DPP4, vildagliptin causes an increase in glucagon like peptide-1 (GLP-1), an intestinal hormone that aids in glucose homeostasis and insulin secretion. The manufacturer of vildagliptin received an approvable letter from the Food and Drug Administration in late February 2007. Vildagliptin has a halflife of about 90 minutes; however, ≥50% of DPP4 inhibition continues for more than 10 hours, allowing for once- or twice-daily dosing. Clinical trials have shown that vildagliptin is effective in significantly lowering glycosylated hemoglobin (HbA1c), fasting plasma glucose, and prandial glucose levels. Beta-cell function may also be improved. The most common adverse effects in patients receiving vildagliptin included headache, nasopharyngitis, cough, constipation, dizziness, and increased sweating. In most studies, the rate of hypoglycemia appeared to be similar to that of placebo.
Conclusion: In clinical trials of patients with type 2 diabetes mellitus, vildagliptin has been shown to reduce HbA1c, fasting plasma glucose levels, prandial glucose levels, and prandial glucagon secretion and to improve ß-cell function. If vildagliptin is approved for marketing, it will add to the available treatment options for diabetes and will provide patients and health care providers with another noninjectable therapy option.
Almost 10% of the U.S. population ages 20 years or older has diabetes mellitus, either diagnosed or undiagnosed. Despite the availability of many different types of medications to treat type 2 diabetes mellitus, less than one half of patients reach target glycosylated hemoglobin (HbA1c) levels. Because of this high prevalence and the difficulty patients experience reaching targets for glycemic control, researchers are actively investigating new agents to improve the management of type 2 diabetes mellitus. Over the past few years, the labeling of a number of new medications for the treatment of diabetes has been approved by the Food and Drug Administration (FDA). These include pramlintide, exenatide, inhaled insulin, insulin glulisine, and insulin detemir.
With the exception of inhaled insulin, none of the other recently approved diabetes medications are administered orally. Although insulin and other injectable therapies are effective treatments, there are often barriers to therapy with injectable medications. Some of these barriers include patient and physician resistance, patients' fear of needles, inconvenience, the complexity of regimens, time, and cost. Because of these barriers to injectable therapy and the increasing incidence of diabetes, more options for oral antidiabetic agents are warranted.
Vildagliptin is among a new class of oral diabetes medications currently being studied. The mechanism of these agents involves inhibition of dipeptidyl peptidase IV (DPP4), the enzyme that contributes to the inactivation of the hormone glucagon like peptide-1 (GLP-1). This inhibition of DPP4 results in increased levels of active GLP-1. GLP-1 is a hormone secreted by the intestines from L cells, the most abundant endocrine cells in the gut, in response to food. In addition to stimulating insulin production, it is thought that GLP-1 secretion slows gastric emptying, inhibits glucagon secretion, and decreases appetite. GLP-1 secretion is significantly reduced in patients with diabetes in response to meal ingestion compared with persons without diabetes. Lower GLP-1 levels in patients with type 2 diabetes mellitus are thought to be a consequence and not a cause of the disease.
GLP-1 has been studied for many years, but research during the past decade has shed more light on a possible role of GLP-1 in the treatment of type 2 diabetes mellitus. The effect of a subcutaneous continuous infusion of GLP-1 versus saline on glycemic control was evaluated over six weeks in patients with type 2 diabetes mellitus. In the group receiving the GLP-1 infusion, a decrease in HbA1c from 9.2% to 7.9% (p = 0.003) was seen, indicating a sustained improvement in glycemic control. In addition, a decrease in mean fasting plasma glucose concentration was observed in the GLP-1 group of 75 mg/dL (4.3 mmol/L) by week 6 (p < 0.0001). From this study, it is evident that GLP-1 can have a significant effect on glucose regulation.
In October 2006, the labeling for sitagliptin (Januvia), a DPP4 inhibitor, was approved by FDA for the treatment of type 2 diabetes mellitus as monotherapy or in combination with metformin or thiazolidinediones. Vildagliptin is not yet approved for marketing in the United States, but the manufacturer announced that it received an approvable letter from FDA in late February 2007. Saxagliptin, another DPP4 inhibitor, is also being investigated. As these novel agents become available for the treatment of type 2 diabetes mellitus, it is important to examine the properties of these drugs. This article reviews the pharmacology, pharmacokinetics, clinical efficacy, drug interactions, and role in therapy of vildagliptin.
Abstract and Introduction
Abstract
Purpose: The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, and role in therapy of vildagliptin for the treatment of type 2 diabetes mellitus were reviewed.
Summary: Vildagliptin is an agent in a new class of medications called dipeptidyl peptidase IV (DPP4) inhibitors. By inhibiting DPP4, vildagliptin causes an increase in glucagon like peptide-1 (GLP-1), an intestinal hormone that aids in glucose homeostasis and insulin secretion. The manufacturer of vildagliptin received an approvable letter from the Food and Drug Administration in late February 2007. Vildagliptin has a halflife of about 90 minutes; however, ≥50% of DPP4 inhibition continues for more than 10 hours, allowing for once- or twice-daily dosing. Clinical trials have shown that vildagliptin is effective in significantly lowering glycosylated hemoglobin (HbA1c), fasting plasma glucose, and prandial glucose levels. Beta-cell function may also be improved. The most common adverse effects in patients receiving vildagliptin included headache, nasopharyngitis, cough, constipation, dizziness, and increased sweating. In most studies, the rate of hypoglycemia appeared to be similar to that of placebo.
Conclusion: In clinical trials of patients with type 2 diabetes mellitus, vildagliptin has been shown to reduce HbA1c, fasting plasma glucose levels, prandial glucose levels, and prandial glucagon secretion and to improve ß-cell function. If vildagliptin is approved for marketing, it will add to the available treatment options for diabetes and will provide patients and health care providers with another noninjectable therapy option.
Introduction
Almost 10% of the U.S. population ages 20 years or older has diabetes mellitus, either diagnosed or undiagnosed. Despite the availability of many different types of medications to treat type 2 diabetes mellitus, less than one half of patients reach target glycosylated hemoglobin (HbA1c) levels. Because of this high prevalence and the difficulty patients experience reaching targets for glycemic control, researchers are actively investigating new agents to improve the management of type 2 diabetes mellitus. Over the past few years, the labeling of a number of new medications for the treatment of diabetes has been approved by the Food and Drug Administration (FDA). These include pramlintide, exenatide, inhaled insulin, insulin glulisine, and insulin detemir.
With the exception of inhaled insulin, none of the other recently approved diabetes medications are administered orally. Although insulin and other injectable therapies are effective treatments, there are often barriers to therapy with injectable medications. Some of these barriers include patient and physician resistance, patients' fear of needles, inconvenience, the complexity of regimens, time, and cost. Because of these barriers to injectable therapy and the increasing incidence of diabetes, more options for oral antidiabetic agents are warranted.
Vildagliptin is among a new class of oral diabetes medications currently being studied. The mechanism of these agents involves inhibition of dipeptidyl peptidase IV (DPP4), the enzyme that contributes to the inactivation of the hormone glucagon like peptide-1 (GLP-1). This inhibition of DPP4 results in increased levels of active GLP-1. GLP-1 is a hormone secreted by the intestines from L cells, the most abundant endocrine cells in the gut, in response to food. In addition to stimulating insulin production, it is thought that GLP-1 secretion slows gastric emptying, inhibits glucagon secretion, and decreases appetite. GLP-1 secretion is significantly reduced in patients with diabetes in response to meal ingestion compared with persons without diabetes. Lower GLP-1 levels in patients with type 2 diabetes mellitus are thought to be a consequence and not a cause of the disease.
GLP-1 has been studied for many years, but research during the past decade has shed more light on a possible role of GLP-1 in the treatment of type 2 diabetes mellitus. The effect of a subcutaneous continuous infusion of GLP-1 versus saline on glycemic control was evaluated over six weeks in patients with type 2 diabetes mellitus. In the group receiving the GLP-1 infusion, a decrease in HbA1c from 9.2% to 7.9% (p = 0.003) was seen, indicating a sustained improvement in glycemic control. In addition, a decrease in mean fasting plasma glucose concentration was observed in the GLP-1 group of 75 mg/dL (4.3 mmol/L) by week 6 (p < 0.0001). From this study, it is evident that GLP-1 can have a significant effect on glucose regulation.
In October 2006, the labeling for sitagliptin (Januvia), a DPP4 inhibitor, was approved by FDA for the treatment of type 2 diabetes mellitus as monotherapy or in combination with metformin or thiazolidinediones. Vildagliptin is not yet approved for marketing in the United States, but the manufacturer announced that it received an approvable letter from FDA in late February 2007. Saxagliptin, another DPP4 inhibitor, is also being investigated. As these novel agents become available for the treatment of type 2 diabetes mellitus, it is important to examine the properties of these drugs. This article reviews the pharmacology, pharmacokinetics, clinical efficacy, drug interactions, and role in therapy of vildagliptin.
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