Addition of Metformin to Sildenafil Treatment for Erectile 2 Dysfunction in Eugonadal Non–diabetic Men with Insulin

25 26 Erection depends largely on the release of nitric oxide (NO) by vascular endothelial cells. 27 Insulin resistance (IR) is a metabolic abnormality that produces endothelial dysfunction 28 characterized by decreased synthesis and release of NO. Aim: To evaluate the effect of 29 treatment with metformin on the response to sildenafil in patients with erectile dysfunction 30 (ED) and IR. Methods: Prospective, randomized, controlled, double-blind placebo study. 31 We included 30 male patients with ED, IR and poor response to sildenafil. Exclusion 32 criteria: pharmacologic, anatomic or endocrine ED, diabetes, prostatic surgery or chronic 33 illnesses. Erectile function was rated according to the International Index of Erectile 34 Function 5 (IIEF-5). IR was measured by HOMA (IR=HOMA ≥3). Patients were 35 randomized to receive metformin (n=17) or placebo (n=13). Results: After treatment with 36 metformin, patients with ED showed a significant increase in IIEF-5 score and a significant 37 decrease in HOMA both occurring at months 2 (IIEF-5: 17.0±6.0 vs. 14.3±3.9, p=0.01 and 38 HOMA: 3.9±1.6 vs. 5.5±2.4, p=0.01) to 4 of treatment (IIEF-5: 19.8±3.8 vs. 14.3±3.9, 39 p=0.005 and HOMA: 4.5±1.9 vs. 5.5±2.4, p=0.04), with no changes in these parameters in 40 patients with ED receiving placebo. Patients treated with metformin had more adverse 41 events than those who received placebo: 61.5% versus 7.7%, p=0.03, respectively. AEs 42 were mild, mainly gastrointestinal, and did not cause discontinuation of treatment. 43 Conclusion: Treatment with metformin in patients with ED and poor response to sildenafil 44 reduced the IR and improved erectile function. 45 46