SGLT2 inhibitors reduced gout incidence by 17–25% in people with type 2 diabetes, while GLP-1 drugs showed no effect on gout rates.
HR 0.75 for gout with SGLT2iAdding an SGLT2 inhibitor to metformin reduced gout incidence by 25% over 5 years in the largest study of its kind
What the researchers found
SGLT2 inhibitors with metformin reduced gout incidence by 25% compared to metformin alone (HR 0.75, p < 0.0001). SGLT2 inhibitors with insulin reduced gout by 17% versus insulin alone (HR 0.83, p < 0.0001).
GLP-1 receptor agonists showed no significant difference in gout incidence versus either metformin or insulin controls.
When SGLT2 inhibitors were compared directly to GLP-1 drugs, they had lower gout rates in both the metformin group (HR 0.77, p < 0.0001) and the insulin group (HR 0.82, p < 0.0001).
Why it matters
Gout is common in type 2 diabetes. SGLT2 inhibitors lower uric acid levels (the chemical that causes gout) as part of how they work. This study provides large-scale real-world evidence that this biochemical effect translates to fewer actual gout episodes. For patients with both diabetes and gout risk, this could tip the scale toward SGLT2 inhibitors.
The numbers in context
- Metformin control: 1,111,449 patients
- SGLT2i + metformin: 101,706 patients
- GLP-1 + metformin: 110,180 patients
- Insulin control: 1,398,066 patients
- SGLT2i + metformin vs metformin: HR 0.75 (95% CI 0.69-0.82, p < 0.0001)
- SGLT2i + insulin vs insulin: HR 0.83 (95% CI 0.74-0.92, p < 0.0001)
- SGLT2i vs GLP-1 (metformin users): HR 0.77 (p < 0.0001)
- SGLT2i vs GLP-1 (insulin users): HR 0.82 (p < 0.0001)
How the study worked
Researchers conducted a cohort study using the TriNetX federated database, an international electronic health records network. They included patients started on metformin or insulin, with or without an SGLT2 inhibitor or GLP-1 drug, at least 2 years before the analysis date. Groups were propensity score matched (1:1) for 26 characteristics. They tracked gout, all-cause mortality (positive control), and herpes zoster (negative control) over 5 years.
Who was studied
Over 2.8 million people with type 2 diabetes from the TriNetX international database, propensity score matched
What this study cannot tell us
This is an observational database study with propensity score matching, not a randomized trial. Residual confounding is possible despite matching for 26 variables. Gout diagnosis in electronic health records may be inconsistent. The TriNetX database may not represent all populations equally. The study compared drug additions rather than head-to-head monotherapy.
How to read the evidence
Rated moderate: massive observational study with propensity score matching provides strong real-world evidence, but it is not a randomized trial.
When this study was published
Published in 2024 using data from the TriNetX international database with 5-year follow-up.
The bigger picture
SGLT2 inhibitors lower uric acid as part of how they work. This study provides large-scale real-world evidence that this biochemical effect translates to fewer actual gout episodes, giving them an advantage for patients with both diabetes and gout risk.
Questions still open
- Should patients with diabetes and gout be preferentially prescribed SGLT2 inhibitors?
- Why don't GLP-1 drugs reduce gout despite their weight loss effects?
Common questions
Which diabetes drugs reduce gout?
Why do SGLT2 inhibitors lower gout risk?
Read the original research
SGLT2 Inhibitors, but Not GLP-1 Receptor Agonists, Reduce Incidence of Gout in People Living With Type 2 Diabetes Across the Therapeutic Spectrum.
Clinical therapeutics, 46(11), 835-840
Citation
Preston, Frank G; Anson, Matthew; Riley, David R; Ibarburu, Gema H; Henney, Alexander; Lip, Gregory Y H; Cuthbertson, Daniel J; Alam, Uazman; Zhao, Sizheng S. (2024). SGLT2 Inhibitors, but Not GLP-1 Receptor Agonists, Reduce Incidence of Gout in People Living With Type 2 Diabetes Across the Therapeutic Spectrum.. Clinical therapeutics, 46(11), 835-840. https://doi.org/10.1016/j.clinthera.2024.06.021