GLP-1 Agonists Do Not Induce Erectile Dysfunction - They May Actually Improve It
GLP-1 receptor agonists do not cause erectile dysfunction (ED) in men with type 2 diabetes; emerging evidence suggests they may actually improve erectile function through multiple mechanisms including weight loss, improved glycemic control, and direct vascular effects. 1, 2
Evidence Supporting Improvement in Erectile Function
The most compelling recent evidence comes from the REWIND trial, which demonstrated that dulaglutide reduced the incidence of moderate or severe ED by 8% (HR 0.92,95% CI 0.85-0.99, p=0.021) compared to placebo in 3,725 men with type 2 diabetes followed over several years. 1 Men treated with dulaglutide also experienced a lesser decline in erectile function scores compared to placebo (least square mean difference of 0.61, p=0.006). 1
A 2024 retrospective cohort study of 108 men with type 2 diabetes and ED found that GLP-1 RAs plus metformin significantly improved IIEF-5 scores by 2.26 points (p<0.0001) after 12 months, compared to metformin alone. 2 This improvement occurred alongside:
- Weight loss of 5.82 kg (p<0.0001) 2
- HbA1c reduction of 0.56% (p<0.0001) 2
- Increased total testosterone by 41.41 ng/dL (p<0.0001) 2
- Increased free testosterone by 0.44 ng/dL (p<0.0001) 2
Mechanisms of Benefit
GLP-1 RAs improve erectile function through several pathways beyond glucose control:
- Direct vascular effects: Preclinical studies show liraglutide reduces oxidative stress, decreases NADPH oxidase and ROS production, and downregulates the RhoA/ROCK2 pathway in corpus cavernosum smooth muscle cells. 3
- Autophagy promotion: GLP-1 RAs enhance autophagy in corpus cavernosum tissue, which may protect against diabetic vascular damage. 3
- Weight reduction: The 2-4 kg weight loss associated with GLP-1 RAs contributes to improved erectile function, as obesity is a major ED risk factor. 4, 2
- Improved endothelial function: GLP-1 RAs enhance endothelium-dependent vasodilation and lower systolic blood pressure by 2-3 mm Hg. 4
Clinical Context: ED Risk Factors in Diabetes
Understanding baseline ED risk in diabetic men is crucial for interpreting GLP-1 RA effects. Diabetic men have a twofold increased ED incidence rate (50 cases/1000 man-years) compared to non-diabetic men. 4 Key risk factors include:
- Autonomic neuropathy (OR 5.0) 4
- Poor glycemic control (OR 2.3) 4
- Diabetes duration (OR 2.0) 4
- Hypertension (OR 2.1) 4
Important Caveats
While GLP-1 RAs show promise for ED, several considerations apply:
- Cardiovascular effects: GLP-1 RAs increase heart rate by 3-10 beats/min, which raised concerns in heart failure studies but has not been problematic in ED contexts. 4
- No effect on heart failure hospitalization: Large cardiovascular outcomes trials showed GLP-1 RAs had neutral effects on HF hospitalization, distinguishing them from medications that worsen ED through volume overload. 4
- Gastrointestinal side effects: Nausea and delayed gastric emptying are common but typically do not impact sexual function directly. 4
Practical Recommendations
When prescribing GLP-1 RAs to diabetic men with ED:
Counsel patients that GLP-1 RAs will not worsen ED and may improve it, particularly with sustained use beyond 12 months. 1, 2
Optimize the therapeutic regimen: The greatest ED improvement occurs when GLP-1 RAs achieve significant weight loss (>5 kg) and HbA1c reduction (<7%). 2
Consider combination therapy: In men with hypogonadism, adding GLP-1 RAs to testosterone replacement therapy and metformin produces superior ED outcomes compared to testosterone and metformin alone. 5
Set realistic expectations: ED improvement is gradual, with measurable benefits typically emerging after 6-12 months of consistent GLP-1 RA therapy. 1, 2
Continue PDE5 inhibitors as first-line ED treatment: GLP-1 RAs complement but do not replace phosphodiesterase-5 inhibitors (sildenafil, tadalafil, vardenafil), which remain the recommended first-line therapy for diabetic ED. 6, 7