SGLT-2 inhibitors associated with lower risk of gout vs. GLP-1 receptor agonists

In a large, propensity-matched study, adult patients with type 2 diabetes who were newly prescribed a sodium-glucose cotransporter-2 (SGLT-2) inhibitor had a lower rate of incident gout than those newly prescribed a glucagon-like peptide-1 (GLP-1) receptor agonist.


Patients with type 2 diabetes who are newly prescribed a sodium-glucose cotransporter-2 (SGLT-2) inhibitor may have a lower risk of gout than those newly prescribed a glucagon-like peptide-1 (GLP-1) receptor agonist, a longitudinal study found.

Researchers used a U.S. nationwide commercial insurance database from March 2013 to December 2017 to compare the rate of gout between adults newly prescribed each type of medication. In a 1:1 ratio, they propensity score matched patients prescribed an SGLT-2 inhibitor with those prescribed a GLP-1 receptor agonist. Patients were excluded from the study if they had a history of gout or had previously received gout-specific treatment. The primary outcome was a new diagnosis of gout. Results were published online on Jan. 14 by Annals of Internal Medicine.

Overall, 295,907 patients met study inclusion criteria. After propensity score matching, 119,530 patients were included in each group. All baseline characteristics were well balanced. The average age was 54 years, 52% of patients were women, two-thirds had hypertension, and about one-quarter had filled a prescription for insulin. Mean follow-up was 302 days in the SGLT-2 inhibitor group and 261 days in the GLP-1 receptor agonist group.

Four hundred eighty-six patients newly prescribed an SGLT-2 inhibitor were subsequently diagnosed with gout (incidence rate, 4.9 events per 1,000 person-years), compared with 665 who were newly prescribed a GLP-1 receptor agonist (incidence rate, 7.8 events per 1,000 person-years), for an adjusted hazard ratio of 0.64 (95% CI, 0.57 to 0.72) and a rate difference of −2.85 (95% CI, −3.59 to −2.12) per 1,000 person-years. Similar results were seen in the cohort of patients with at least 365 days of baseline data, and results were consistent irrespective of sex, age, or baseline diuretic use.

Sensitivity analyses yielded similar results. In the sensitivity analysis of propensity score-matched patients with up to one year of index medication exposure, 524 patients receiving an SGLT-2 inhibitor (n=119,813) and 712 receiving a GLP-1 receptor agonist (n=119,813) were diagnosed with gout (5.6 vs. 7.7 events per 1,000 person-years, respectively), for an adjusted hazard ratio of 0.73 (95% CI, 0.66 to 0.82). In the sensitivity analysis of propensity score-matched new users of SGLT-2 inhibitors (n=97,442) versus new users of dipeptidyl peptidase-4 inhibitors (n=97,442), the hazard ratio for gout associated with an SGLT-2 inhibitor was 0.66 (95% CI, 0.58 to 0.75).

The study authors noted the potential for unmeasured confounding and the relatively short duration of follow-up, among other limitations. They added that while SGLT-2 inhibitors may reduce a patient's risk for gout, they are associated with adverse events, such as genital infection, which affects about 7% of users.

Nonetheless, the results were robust across sensitivity analyses and are unlikely to be explained by unmeasured confounding, the authors concluded. “Future studies are necessary to confirm our findings, and if replicated, SGLT-2 inhibitors might be an effective class of medication for the prevention of gout for patients with diabetes or metabolic disorders,” they wrote.