Effects of Diazoxide-mediated Insulin Suppression on Glucose and Lipid metabolism in Non-Diabetic Obese Men.

Effects of Diazoxide-mediated Insulin Suppression on Glucose and Lipid metabolism in Non-Diabetic Obese Men.

J Clin Endocrinol Metab. 2018 Mar 29;:

Authors: Loves S, van Groningen L, Filius M, Mekking M, Brandon T, Tack CJ, Hermus A, de Boer H

Abstract
Introduction: It has been suggested that stimulation of lipolysis by Diazoxide (DZX)-mediated insulin suppression may be useful as a treatment of obesity. However, the optimal dose to promote lipolysis without causing hyperglycemia is currently unknown.
Aim: To assess the effects of DZX in non-diabetic obese men on lipid and glucose metabolism.
Methods: Double-blind, placebo-controlled, 6-month trial in men with a BMI of 30 - 37.5 kg/m2 treated with a combination of caloric restriction, a standardized exercise program, and DZX or placebo dose escalation.
Results: The mean maximal tolerated dose (MTD) of DZX was 422 ± 44 mg/day (range 200 - 700 mg/day). Dose limiting events were edema (n = 11), hyperglycemia (n = 6) and nausea (n = 2). After dose reduction to a level free of clinical side effects, DZX treatment was associated with a markedly greater decrease in fasting insulin levels than placebo (-72.3 ± 3.5 % vs -23.0 ± 12.6 %, P <0.001), and a significant improvement of blood pressure and plasma lipid levels. The decline in insulin levels occurred at the cost of a small rise in plasma glucose (0.6 ± 0.2 mmol/l vs -0.1 ± 0.1 mmol/l, P = 0.04) and HbA1c (0.2 ± 0.1 % vs 0.0 ± 0.1 %, P = 0.17).
Conclusion: In non-diabetic obese men, insulin levels can be reduced up to 70% without major metabolic side effects. The marked inter-subject variation in MTD indicates that DZX dose titration needs to be individualized.

PMID: 29618011 [PubMed - as supplied by publisher]

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