Can Diabetes Drugs Do Good Things and Still Have Sexual Side Effects?

As if men with type 2 diabetes didn't have enough to worry about, recent research indicates metformin, a commonly prescribed oral antidiabetic medication that helps control the amount of sugar in the blood, decreases testosterone levels in men with type 2 diabetes. Low testosterone is one possible contributor to erectile dysfunction (ED).

Research published in a 2021 edition of Diabetes Care showed that in a randomized controlled study of 70 men with type 2 diabetes, one month of metformin treatment decreased testosterone significantly. Additionally, the researchers noted long-term effects of metformin on testosterone and sexual function need further study.

A 2016 study suggested metformin leads to a significant reduction in testosterone levels and sex drive, and the onset of low-T-induced ED. On the other hand, the study found sulfonylurea, another diabetes medication, led to a significant increase in testosterone levels, sex drive and erectile function.

Other studies indicate metformin may help improve a man's erectile function because it helps manage the side effects of diabetes that lead to ED. Research published in Translational Andrology and Urology found metformin had positive effects on both activating the nitric oxide response needed to increase blood flow to the penis and moderating sympathetic nerve activity.

'The data is very conflicting, and there's no strong evidence for or against either metformin, sulfonylureas, insulin or any of the other treatment options.'

Due to the limited—and conflicting—research on the subject, some urologists are reluctant to support the notion that diabetes drugs have a significant impact on sexual function.

Neel Parekh, M.D., a clinical assistant professor of urology at the Cleveland Clinic Foundation, said when he reviews the medication lists of patients with ED, he doesn't get too concerned about diabetes drugs.

"The data is very conflicting, and there's no strong evidence for or against either metformin, sulfonylureas, insulin or any of the other treatment options," Parekh said. "Most of these guys who are on medication for the diabetes are also on multiple other medications for blood pressure or cholesterol or other issues that are more likely having a negative effect on the erections than any of the diabetes medications."

Parekh instead focuses on counseling patients with diabetes about the side effects of those other medications, as well as the importance of exercise, blood pressure control and diabetes control.

The cure is not worse than the disease

Currently, there's not enough evidence to say metformin is harmful to erections, said Petar Bajic, M.D., a urologist at the Center for Men's Health in the Glickman Urological & Kidney Institute at the Cleveland Clinic.

"I would say that there is clear evidence across the board that diabetes is a major risk factor for erectile dysfunction, and that the better the diabetic control is, the less likely that erectile dysfunction will progress," Bajic said. "It would make sense that if somebody were to be put on metformin, and that then improved their diabetes, the erectile dysfunction would then be less likely to worsen and could potentially improve to some degree."

One of the issues is that it's quite difficult to tease out the underlying condition (diabetes) from the therapies (metformin and other diabetes drugs), according to Martin Kathrins, M.D., an assistant professor of surgery at Harvard Medical School and a urologist at Brigham and Women's Hospital in Boston.

"Is the cure worse than the disease? I would say no," Kathrins said. "We know that uncontrolled diabetes is part of that 70 percent share of cardio-metabolic syndromes that can contribute to erectile dysfunction. To say that the treatment of this debilitating condition is further contributing to erectile dysfunction or hormonal dysfunction, I think it kind of misses the point. I think patients should be aggressive about controlling the underlying condition to avoid microvascular damage in the penis."

Diabetes is an erection buster

Men with diabetes are probably the most common group of patients who develop ED, said Laurence Levine, M.D., a professor of urology at Rush University Medical Center in Chicago. He added 75 percent to 85 percent of men with diabetes will start to notice some degree of ED within five to seven years of their diagnosis.

Levine called diabetes one of the four main "erection busters"—smoking, hypertension and elevated cholesterol are the other three—that accelerate atherosclerotic changes in blood vessels throughout the body. This erection-busting action is likely because even men who control their diabetes well can experience vascular changes that affect the tiny blood vessels of the penis—and those changes are likely going to precede changes in other areas, such as the larger coronary arteries of the heart.

In response to the studies suggesting diabetes medications may lead to either increased or decreased testosterone levels, Bajic pointed out that 90 percent of ED cases are not primarily due to testosterone.

"Testosterone is an important hormone, but it's almost never the primary cause of ED," he said. "ED is a blood-flow problem. If a man has testosterone within the normal range, and it goes up by a hundred or down by a hundred, it is very unlikely to make any meaningful difference, unless that then pushed him into the low range. Whether or not a drug makes an impact on testosterone does not necessarily mean it makes any meaningful impact on sexual function."