A three-month course of sildenafil, marketed as Viagra® and other brand names, improved insulin sensitivity in people with prediabetes, according to a study published online November 18, 2015, in the Journal of Clinical Endocrinology & Metabolism. The drug also improved fibrinolytic balance and decreased urinary albumin excretion.
“We need additional strategies to help slow the progression from prediabetes to diabetes,” said co-senior author Nancy J. Brown, MD, of Vanderbilt University School of Medicine in Nashville, TN. “Weight loss and exercise regimens can be difficult to maintain, and some current medications have been limited by concerns about adverse effects. Sildenafil and related drugs could offer a potential avenue for addressing the rising number of diabetes diagnoses.”
Scientists know that cyclic GMP (cGMP) increases insulin sensitivity. But the enzyme phosphodiesterase 5 (PED5) breaks down cGMP. Sildenafil, however, inhibits PED5. The researchers speculated that treating patients at risk for diabetes with sildenafil could increase levels of cGMP, and thus increase insulin sensitivity. Other drugs to increase levels of cGMP in the body also are in development.
In this study, Dr. Brown and colleagues randomized 51 overweight individuals with prediabetes to either sildenafil treatment (25 mg three times a day) or matching placebo for 3 months. Study participants underwent a hyperglycemic clamp prior to and at the end of treatment to assess glucose-stimulated insulin secretion and estimate insulin sensitivity. Urine samples were also collected to measure albumin and creatinine.
Among the 42 participants who completed the study, those treated with sildenafil had higher levels of insulin sensitivity than those who took placebo. Participants in the sildenafil group also had lower levels of urinary albumin, which indicated a lower risk for kidney and heart disease.
“Because existing drug therapies to prevent type 2 diabetes can have negative effects on the heart or be of limited use in patients with kidney disease, strategies to prevent diabetes without adversely affecting the risk of kidney and heart disease could have a large impact on public health,” Dr. Brown said. “Further studies will be needed to determine whether long-term treatment with drugs like sildenafil can prevent the onset of diabetes in high-risk patients.”