The Diabetic Risks of 5-alpha Reductase Inhibitor Exposure

5-alpha reductase inhibitor class of targeted medications used to treat an already at-risk population could be contributing to worsening health.

Literature from a past study about the effects of dutasteride, a steroidal 5-alpha reductase inhibitor, to the body suggest that it plays a role in the pathophysiology of diabetes progression in the form of inducing insulin resistance and promoting steatosis. Dutasteride and its medication class partner finasteride are two commonly prescribed drugs for elderly men with benign prostatic hyperplasia. As older age predisposes patients to a higher risk of developing diabetes it is important to understand what other factors play a key role in this specific patient population to reduce those risks as much as possible.

A recent population based cohort study aimed to determine any association between incidence of newly diagnosed type 2 diabetes mellitus and long term steroidal 5-alpha reductase inhibitor use. Data for this study was obtained from a national registry of medical records from hundreds of primary care practices out of the United Kingdom. Patients were enrolled into this study from the massive databank if they were at least 40 years of age, had a recorded diagnosis of benign prostatic hyperplasia, and had been prescribed either dutasteride, finasteride, or tamsulosin; patients were excluded if they were considered pre-diabetic. Data from patients taking tamsulosin was obtained in order to act as a “control” and compare to the data from the 5-alpha reductase inhibitor treatment arm. Data was collected over the course of 11 years.

The primary endpoint in this study was incidence of newly diagnosed type 2 diabetes mellitus as documented by a primary care provider in a patient chart, new prescriptions of oral medications that work to lower glucose, or new prescriptions of insulin. Patients that were included in either of the two 5-alpha reductase inhibitor cohorts were generally older and had more existing comorbidities than the patients included in the tamsulosin cohort; baseline patient characteristics were similar between the two groups in the 5-alpha reductase inhibitor cohort. A total of 55,275 patients were included in primary analysis: 8,231 in the dutasteride cohort, 30,774 in the finasteride cohort, and 16,270 in the tamsulosin cohort.

Over the 11 year data collection period, a total of 2,081 new cases of diabetes were recorded within the study population: 368 (4.5%) in the dutasteride cohort, 1,207 (3.9%) in the finasteride cohort, and 506 (3.1%) in the tamsulosin cohort with the mean follow-up time for these new diagnoses being 5.2 years. Cumulative incidence of newly diagnosed type 2 diabetes was higher in the 5-alpha reductase inhibitor cohorts than the tamsulosin cohort (p<0.001) though the difference between the two 5-alpha reductase inhibitor cohorts were not significant.

The researchers of this study wanted to try and replicate the results discovered from the data pulled from the large database out of the United Kingdom, so they mimicked the exact same methods with another data set pulled from the Taiwanese National Health Insurance Research Database. Compared to the average patients out of the United Kingdom, patients from Taiwan were generally younger with fewer comorbidities. Replication was successful as similar trends between study cohorts were observed: patients taking 5-alpha reductase inhibitors for benign prostatic hyperplasia posed a greater risk of developing diabetes than patients taking tamsulosin for the same indication.

While tamsulosin is still the first-line treatment option for men with symptomatic benign prostatic hyperplasia, 5-alpha reductase inhibitors are still commonly used for patients with more severe symptoms. Prescribing this class of medication with caution in patients already at risk for metabolic diseases such as type 2 diabetes should be practiced by health care providers.

Practice Pearls

• Patients taking dutasteride or finasteride for control of benign prostatic hyperplasia are at a 32% and 26% increased risk, respectively, for developing type 2 diabetes than patients taking tamsulosin for the same indication.
• Data from this study was a pooled effort from nationally recognized health registration databanks from two different countries with similar reproducible results.
• There was no significant difference in the risk of developing type 2 diabetes in men with benign prostatic hyperplasia taking either dutasteride or finasteride.

Reference: Wei L, Lai EC, Kao-Yang YH, et al. Incidence of type 2 diabetes mellitus in men receiving steroid 5-alpha reductase inhibitors: a population based cohort study. British Medical Journal 2019;365:1204. DOI: 10.1136/bmj.l1204

Adam Chalela, B.S. Doctor of Pharmacy Candidate USF College of Pharmacy