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Sildenafil Possible Treatment For Prediabetes

Treatment improves insulin sensitivity, lowers risk of heart and kidney disease.

The objective was to test the hypothesis that chronic phosphodiesterase 5 inhibition with nizagara(sildenafil) improves insulin sensitivity and secretion without diminishing fibrinolytic function.

In people with type 2 diabetes, insulin resistance is the major problem. Patients can not produce enough of insulin, so muscle, fat, and liver cells do not easily absorb sugar from the blood stream. Many people with prediabetes do not know they have insulin resistance until they develop type 2 diabetes, which is a lifelong disease. The American Diabetes Association (ADA) recommends that testing to detect prediabetes be considered in adults who are overweight or obese and have one or more additional risk factors for diabetes.

Prediabetic patients are always encouraged to keep a good lifestyle and form a healthy eating habit. A new study published in the Endocrine Society’s Journal of Clinical Endocrinology and Metabolism showed that the medication sildenafil, which indicates for erectile dysfunction, improve insulin sensitivity in individuals with prediabetes, and it also reduces the risk of kidney and heart diseases.

As most men with diabetes eventually have some form of sexual dysfunction due to elevated blood sugars, this treatment of a phosphodiesterase 5 inhibition could provide other benefits.

This is a randomized, double blind, placebo control study conducted at Vanderbilt Clinical Research center. A total of 42 people with prediabetes who were overweight completed the study. There were 21 participants in the treatment group who received sildenafil 25 mg three times a day for 3 months. Researchers focused on the outcomes of insulin sensitivity and glucose-stimulated insulin secretion.

Twenty-one subjects completed each treatment arm. After 3 months, the insulin sensitivity index was significantly greater in the sildenafil group compared to the placebo group.  In contrast, there was no effect of 3-month treatment with sildenafil on acute- or late-phase glucose-stimulated insulin secretion.

Sildenafil decreased plasminogen activator inhibitor-1 without altering tissue-plasminogen activator. In contrast to placebo, sildenafil also decreased the urine albumin-to-creatinine ratio from 12.67 to 6.84.   This effect persisted 3 months after sildenafil discontinuation.

In individuals with prediabetes, 3-month treatment with the PDE5 inhibitor sildenafil improves insulin sensitivity, but does not alter GSIS measured rigorously using hyper-

glycemic clamps. The favorable effect of sildenafil on insulin sensitivity is accompanied by an improvement in fibrinolytic balance and decreased urinary albumin excretion.

Two prior studies have reported a favorable effect of tadalafil on DI after 3-week and 3-month  treatments. The finding that sildenafil tended to increase DI in the current study suggests that this is a class effect of PDE5 inhibitors.

Three-month treatment with sildenafil decreased circulating PAI-1 concentrations. Both glucose and insulin stimulate response elements in the PAI-1 promoter, leading to increased circulating PAI-1 concentrations during insulin resistance. Thus, a decrease in PAI-1 may reflect improved insulin sensitivity. In addition, inhibiting the degradation of cGMP per se might be expected to decrease circulating PAI-1 concentrations because cGMP decreases PAI-1 expression.

Fibrinolytic balance is one measure of endothelial function. Albuminuria may also represent generalized endothelial dysfunction. In addition, albuminuria may

predict incident type 2 diabetes in high-risk groups. PDE5 inhibition reduces albuminuria and glomerular injury in rodent models. PDE5 is expressed in proximal

tubules, collecting ducts, and the glomerulus.

In conclusion, our study suggests that chronic PDE5 inhibition improves insulin sensitivity, fibrinolytic balance, and albuminuria in subjects with prediabetes. Further studies will be needed to determine whether long-term treatment with drugs that increase cGMP can prevent the onset of diabetes in high-risk patients.

The results stated those who were treated with sildenafil showed greater insulin sensitivity index with p value 0.049, but there was no effect of this three-month treatment on acute or late-phase glucose-stimulated insulin secretion. Other than that, researchers found sildenafil also decreased the urine albumin-to-creatine ratio, which indicated the risk of kidney and heart disease. The author mentioned those findings had a large impact on public health because it was an important strategy to prevent diabetes without adversely affecting the risk of kidney and heart disease.

Practice Pearls:

  • A randomized, double blind, placebo control study of overweight patients with prediabetes showed how sildenafil affects insulin sensitivity.
  • The results showed sildenafil improved insulin sensitivity and lowered the risk of kidney and heart disease.
  • These findings provide a strategy that can prevent diabetes without hurting the kidney and heart.

Ramirez CE, Hui N, Yu C et al. “Treatment with Sildenafil Improves Insulin Sensitivity in Prediabetes: A Randomized, Controlled Trial.” Journal of Clinical Endocrinology & Metabolism. 2015.