The use of sodium-glucose cotransporter-2 (SGLT2) inhibitors vs glucagon-like peptide-1 receptor agonists (GLP1-RA) is associated with a 50% reduced risk for gout, according to study results published in Pharmacoepidemiology and Drug Safety.
Researchers of the current study sought to evaluate the association between SGLT2 inhibitors and gout, using a cohort study design and a symmetry analysis.
An active-comparator, new-user cohort study was conducted using the Danish nationwide health registries. Risk for incident gout among SGLT2 inhibitors initiators was compared with a propensity score-matched cohort of GLP1-RA initiators. A corresponding symmetry analysis was used to address any potential unmeasured confounding issues.
Eligible individuals included those who had filled their first prescription for an SGLT2 inhibitor or a GLP1-RA between January 1, 2013, and December 31, 2018. All study participants were followed up with for up to 3 years. Participants were assumed to be exposed from the time that their first prescription was received during follow-up (SGLT2 inhibitor or GLP1-RA), regardless of discontinuation or medication switching, which was consistent with an intention-to-treat (ITT) approach.
The study outcome of interest was gout, which was measured by initiation of any uric acid-lowering therapy (ULT), colchicine, or a first hospital diagnosis of gout. A total of 11,562 pairs of SGLT2 inhibitor users and GLP1-RA users were identified, which contributed to 43,927 person-years of follow-up.
In the main analysis —ITT with follow-up capped at 3 years — incident rates of gout of 4.8 and 9.1 events per 1000 person-years were reported among SGLT2 inhibitor users and GLP1-RA users, respectively, yielding an incidence rate difference (IRD) of
-4.3 events per 1000 person-years (95% CI, -5.9 to -2.8 per 1000 person-years). The hazard ratio (HR) was 0.52 (95% CI, 0.41-0.66).
The per-protocol analysis had a similar HR as the main analysis 0.49 (95% CI, 0.33-0.71) and an IRD of -3.4 events per 1000 person-years (95% CI, -5.1 to -1.6 per 1000 person-years). Of 420 individuals who initiated ULT, only 5 received a diagnosis of urolithiasis prior to initiation of treatment.
In the symmetry analysis, a total of 118 participants initiated SGLT2 inhibitors after a gout diagnosis; 80 individuals initiated treatment prior to a diagnosis of gout. The trend-adjusted sequence ratio (SR) was 0.68 (95% CI, 0.51-0.91). The crude SR for GLP1-RAs was 0.98 (95% CI, 0.82-1.18). The active comparator-adjusted SR for SGLT2 inhibitors was 0.67 (95% CI, 0.44-0.86) for a 1-year window. Further, the SRs for observation windows of 180 days and 900 days were comparable in magnitude.
A major limitation of the current study was the fact that the outcome definition relied mainly on new use of ULT or colchicine and was unable to capture any gout events that were treated with nonsteroidal anti-inflammatory drugs or glucocorticoids. Moreover, the outcome variable had not been validated.
Researchers concluded, “The findings [of this study] are comparable to prior studies addressing this association.”
Disclosures: Some study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Lund LC, Højlund M, Henriksen DP, Hallas J, Kristensen KB. Sodium-glucose cotransporter-2 inhibitors and the risk of gout: a Danish population based cohort study and symmetry analysis. Pharmacoepidemiol Drug Saf. Published online April 21, 2021. doi:10.1002/pds.5252