REVIEW OF: Dieperink E et al, Am J Addict 2021;30(6):570–577

STUDY TYPE: Retrospective cohort study

Some preclinical data suggest that pioglitazone (Actos), a medication commonly prescribed for type 2 diabetes, might be helpful for the treatment of addictive disorders, including alcohol use disorder (AUD). The purported mechanism is peroxisome proliferator–activated receptor-gamma agonism, which sensitizes the body to the effects of insulin but also might decrease substance cravings. A recent study sought more information about this medication by using a retrospective chart review to see if pioglitazone was associated with decreased drinking.

The authors used the Veterans Administration (VA) electronic medical record to identify 49 men with type 2 diabetes who had an Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) score ≥3 prior to starting pioglitazone. The AUDIT-C is a three-question scale designed to identify unhealthy alcohol use, defined as a score ≥4 for men or ≥3 for women (Bradley KA et al, Alcohol Clin Exp Res 2007;31(7):1208–1217). The VA health care system mandates annual AUDIT-C scores on all patients, making it a convenient metric for researchers to follow over time.

The participants were predominantly White (81.6%) and had a mean age of 67 years. Three of the subjects met criteria for AUD. Pioglitazone doses were 30–45 mg, typical for type 2 diabetes treatment, and the medication was prescribed for an average of 78.5 months. The primary outcome was change in AUDIT-C score after starting pioglitazone.

The mean AUDIT-C score prior to starting pioglitazone was 3.98 (95% confidence interval [CI]: 3.51–4.44), which decreased to 2.89 (95% CI: 2.46–3.32) while on the medication. Though relatively modest, this absolute change of 1.09 was statistically significant (p = <0.001). Sub-analysis showed that the greatest reduction in alcohol intake occurred during the first 12–18 months of starting pioglitazone (p = 0.013), with relatively stable alcohol use thereafter. Limitations of the study include its retrospective nature, lack of a control group, and lack of diversity within the cohort.

CARLAT TAKE

This limited study found a small though statistically significant decrease in AUDIT-C scores in patients taking pioglitazone. While the findings are intriguing, the clinical significance of this finding remains to be seen. Therefore, large-scale randomized controlled trials are needed before pioglitazone can be recommended as an AUD treatment.