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A randomized, placebo-controlled, double-blind, prospective trial to evaluate the effect of vildagliptin in new-onset diabetes mellitus after kidney transplantation.

Haidinger M, Werzowa J, Voigt HC, Pleiner J, Stemer G, Hecking M, Döller D, Hörl WH, Weichhart T, Säemann MD - Trials (2010)

Bottom Line: Additionally, vildagliptin has been shown to be safe in patients with moderately impaired kidney function.The primary endpoint is the difference in the 2 h glucose value between baseline and the repeated OGTT performed 3 months after treatment start, compared between the vildagliptin- and the placebo-group.The safety of vildagliptin in renal transplant patients will be assessed by the number of symptomatic hypoglycemic episodes (glucose <72 mg/dl or 4 mmol/l), the number of adverse events, and possible medication-associated side-effects.

View Article: PubMed Central - HTML - PubMed

Affiliation: Clinical Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, Austria.

ABSTRACT

Background: New-onset diabetes mellitus after transplantation (NODAT), a frequent and serious complication after transplantation, is associated with decreased graft and patient survival. Currently, it is diagnosed and treated primarily according to existing guidelines for type II diabetes. To date, only a few trials have studied antidiabetic drugs in patients with NODAT. Vildagliptin is a novel dipeptidyl peptidase-4 (DPP-4) inhibitor that improves pancreatic islet function by enhancing both α- and β-cell responsiveness to increased blood glucose. Experimental data show potential protective effects of DPP-4 inhibitors on islet function after exogenous stress stimuli including immunosuppressants. Therefore, the therapy of NODAT with this class of compounds seems attractive. At present, vildagliptin is used to treat type II diabetes as monotherapy or in combination with other antidiabetic drugs, since that it efficiently decreases glycated hemoglobin (HbA1c) values. Additionally, vildagliptin has been shown to be safe in patients with moderately impaired kidney function. This study will evaluate the safety and efficacy of vildagliptin monotherapy in renal transplant recipients with recently diagnosed NODAT.

Methods/design: This study is a randomized, placebo-controlled, double-blind, prospective phase II trial. Using the results of routinely performed oral glucose tolerance tests (OGTT) in stable renal transplant patients at our center, we will recruit patients without a history of diabetes and a 2 h glucose value surpassing 200 mg/dl (11.1 mmol/l). They are randomized to receive either 50 mg vildagliptin or placebo once daily. A total of 32 patients with newly diagnosed NODAT will be included. The primary endpoint is the difference in the 2 h glucose value between baseline and the repeated OGTT performed 3 months after treatment start, compared between the vildagliptin- and the placebo-group. Secondary endpoints include changes in HbA1c and fasting plasma glucose (FPG). The safety of vildagliptin in renal transplant patients will be assessed by the number of symptomatic hypoglycemic episodes (glucose <72 mg/dl or 4 mmol/l), the number of adverse events, and possible medication-associated side-effects.

Discussion: NODAT is a severe complication after kidney transplantation. Few trials have assessed the safety and efficacy of antidiabetic drugs for these patients. The purpose of this study is to assess the safety and efficacy of vildagliptin in renal transplant patients with NODAT.

Trial registration: ClinicalTrials.gov NCT00980356.

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Related in: MedlinePlus

Flowchart of the Study.
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Figure 1: Flowchart of the Study.

Mentions: Patients with a stable kidney allograft, more than 6 months after transplantation, without a history of T1DM or T2DM routinely undergo an OGTT at our outpatient department. All patients with a pathological OGTT (serum glucose levels ≥ 200 mg/d (11.1 mmol/L)) are classified as patients suffering from NODAT. 32 Patients eligible for the study are invited to the outpatient clinic and therapeutic options are discussed. Patients who are willing to take part in the study and have signed their informed consent form are randomized in a 1:1 ratio into study arm A (vildagliptin) or study arm B (placebo). The detailed study flow chart and an overview of study procedures are depicted in Figure 1 and 2, respectively.


A randomized, placebo-controlled, double-blind, prospective trial to evaluate the effect of vildagliptin in new-onset diabetes mellitus after kidney transplantation.

Haidinger M, Werzowa J, Voigt HC, Pleiner J, Stemer G, Hecking M, Döller D, Hörl WH, Weichhart T, Säemann MD - Trials (2010)

Flowchart of the Study.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2984585&req=5

Figure 1: Flowchart of the Study.
Mentions: Patients with a stable kidney allograft, more than 6 months after transplantation, without a history of T1DM or T2DM routinely undergo an OGTT at our outpatient department. All patients with a pathological OGTT (serum glucose levels ≥ 200 mg/d (11.1 mmol/L)) are classified as patients suffering from NODAT. 32 Patients eligible for the study are invited to the outpatient clinic and therapeutic options are discussed. Patients who are willing to take part in the study and have signed their informed consent form are randomized in a 1:1 ratio into study arm A (vildagliptin) or study arm B (placebo). The detailed study flow chart and an overview of study procedures are depicted in Figure 1 and 2, respectively.

Bottom Line: Additionally, vildagliptin has been shown to be safe in patients with moderately impaired kidney function.The primary endpoint is the difference in the 2 h glucose value between baseline and the repeated OGTT performed 3 months after treatment start, compared between the vildagliptin- and the placebo-group.The safety of vildagliptin in renal transplant patients will be assessed by the number of symptomatic hypoglycemic episodes (glucose <72 mg/dl or 4 mmol/l), the number of adverse events, and possible medication-associated side-effects.

View Article: PubMed Central - HTML - PubMed

Affiliation: Clinical Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, Austria.

ABSTRACT

Background: New-onset diabetes mellitus after transplantation (NODAT), a frequent and serious complication after transplantation, is associated with decreased graft and patient survival. Currently, it is diagnosed and treated primarily according to existing guidelines for type II diabetes. To date, only a few trials have studied antidiabetic drugs in patients with NODAT. Vildagliptin is a novel dipeptidyl peptidase-4 (DPP-4) inhibitor that improves pancreatic islet function by enhancing both α- and β-cell responsiveness to increased blood glucose. Experimental data show potential protective effects of DPP-4 inhibitors on islet function after exogenous stress stimuli including immunosuppressants. Therefore, the therapy of NODAT with this class of compounds seems attractive. At present, vildagliptin is used to treat type II diabetes as monotherapy or in combination with other antidiabetic drugs, since that it efficiently decreases glycated hemoglobin (HbA1c) values. Additionally, vildagliptin has been shown to be safe in patients with moderately impaired kidney function. This study will evaluate the safety and efficacy of vildagliptin monotherapy in renal transplant recipients with recently diagnosed NODAT.

Methods/design: This study is a randomized, placebo-controlled, double-blind, prospective phase II trial. Using the results of routinely performed oral glucose tolerance tests (OGTT) in stable renal transplant patients at our center, we will recruit patients without a history of diabetes and a 2 h glucose value surpassing 200 mg/dl (11.1 mmol/l). They are randomized to receive either 50 mg vildagliptin or placebo once daily. A total of 32 patients with newly diagnosed NODAT will be included. The primary endpoint is the difference in the 2 h glucose value between baseline and the repeated OGTT performed 3 months after treatment start, compared between the vildagliptin- and the placebo-group. Secondary endpoints include changes in HbA1c and fasting plasma glucose (FPG). The safety of vildagliptin in renal transplant patients will be assessed by the number of symptomatic hypoglycemic episodes (glucose <72 mg/dl or 4 mmol/l), the number of adverse events, and possible medication-associated side-effects.

Discussion: NODAT is a severe complication after kidney transplantation. Few trials have assessed the safety and efficacy of antidiabetic drugs for these patients. The purpose of this study is to assess the safety and efficacy of vildagliptin in renal transplant patients with NODAT.

Trial registration: ClinicalTrials.gov NCT00980356.

Show MeSH
Related in: MedlinePlus