Effects of vildagliptin compared with glibenclamide on glucose variability after a submaximal exercise test in patients with type 2 diabetes: study protocol for a randomized controlled trial, DIABEX VILDA

Aline Fofonka, Jorge Pinto Ribeiro, Karina Rabello Casali, Beatriz D Schaan, Aline Fofonka, Jorge Pinto Ribeiro, Karina Rabello Casali, Beatriz D Schaan

Abstract

Background: Cardiovascular disease, endothelial dysfunction, and oxidative stress are common complications among patients with type 2 diabetes (T2DM). In addition to the average blood glucose concentration, glycemic variability may be an important factor for the development of chronic diabetes complications. Patients with T2DM are treated with various types of oral glucose-lowering drugs. Exercise is considered to benefit the health of both healthy and unhealthy individuals, which has been confirmed by a number of scientific research studies in which the participants' health improved. Our general aim in this study will be to evaluate glucose variability after submaximal exercise test in patients receiving treatment with either vildagliptin or glibenclamide. The specific aims of this study are to evaluate the oxidative stress, endothelial function, and metabolic and cardiovascular responses to exercise under treatment with vildagliptin or glibenclamide. All these responses are important in patients with T2DM.

Methods/design: This study is a PROBE (Prospective, Randomized, Open-label, Blinded-Endpoint) design clinical trial. The estimated sample needed is 20 patients with T2DM. In addition to the routine treatment (metformin), patients will receive a second drug orally for 12 weeks: the METV group will receive metformin plus vildagliptin (50 mg twice daily), and the METG group will receive metformin plus glibenclamide (5 to 10 mg twice daily.). Before and after intervention, evaluation of glycemic variability, endothelial function, oxidative stress, and metabolic and cardiovascular response will be performed at rest, during and after a submaximal exercise test (30 minutes, with an intensity based at 10% under the heart rate at the second threshold).

Discussion: In addition to drug treatment, exercise is recommended for treatment of glycemic control in patients with T2DM, especially for its beneficial effects on blood glucose and HbA1c. Few studies have determined the effects of the association between exercise and oral glucose-lowering drugs. The study will be conducted to assess the metabolic and cardiovascular responses at rest, and during and after submaximal exercise in patients receiving one of two oral glucose-lowering drugs (vildagliptin or glibenclamide).

Trial registration: ClinicalTrials.gov Identifier: NCT01867502 study release date: May-17-2013.

Figures

Figure 1
Figure 1
Flow diagram of the study design. # The submaximal exercise test (SET) will occur on the day 2 of a 3-day period of tests. METV group: 12 week s of treatment with vildagliptin added to metformin; METG group: 12 weeks of treatment with glibenclamide added to metformin. *500 to 2000 mg/day according to tolerance; **50 mg twice daily; ***10 to 20 mg twice daily. ABPM: ambulatory blood pressure monitoring, CO: cardiac output, CGMS: continuous glucose monitoring system; BS: blood sample; HRV: heart rate variability, MET: maximal exercise test. †Metabolic evaluation: glucose, HbA1c, insulin, glucagon-like peptide 1 (GLP-1).

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