An Exploratory Study to Evaluate the Effects of Roflumilast on Insulin Sensitivity and Metabolic Parameters in Prediabetic Overweight and Obese Individuals

National Heart, Lung, And Blood Institute

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Abstract

In this study, we will try to understand the effect of PDE4 inhibitor roflumilast on insulin sensitivity. Each study participant will receive oral roflumilast (250 microgram, once a day for 2 week, followed by 500 microgram once a day for four weeks). At baseline and after the 6-week treatment period, we will assess insulin sensitivity (hyperinsulinemic euglycemic glucose clamp technique, glucose clamp). In addition, cell function, skeletal muscle mitochondrial function, vascular function, body composition, and circulating adipocytokine profile will be measured at baseline and after treatment to evaluate potential changes that may be related to improvements in metabolic function. Vascular function is not only an indicator of insulin sensitivity, but is also important for glucose delivery and metabolism. Regarding vascular function, we will measure basal and insulin-stimulated brachial artery blood flow (large conduit artery assessed by Doppler ultrasound) as well as capillary recruitment in forearm skeletal muscle (small nutritive arterioles assessed by ultrasound with microbubble contrast). This study will explore whether roflumilast is effective at improving insulin sensitivity in pre-diabetic individuals. Results from this study may have important implications for the potential use of roflumilast in treating type 2 diabetes. We have analyzed two subjects (out of 15 total planned) and will continue to recruit over the next year.