SGLT2 Inhibitors and Gout Prevention

Will this standard type 2 diabetes treatment change the treatment choice for patients with gout?

 Sodium-glucose transport protein 2 (SGLT-2) inhibitors are a staple in treating patients with type 2 diabetes. These drugs were designed for use in patients with type 2 diabetes. It reduces blood glucose levels by helping excrete the sugar through the urine. These medications help not only with lowing blood glucose in these patients but can also lower blood urate levels. This is especially important in people with diabetes due to their common risk of developing hyperuricemia because of their decreased ability to secrete urate through their urine. However, until recently, there has been no known connection between these treatments and gout incidence. This is what a recent study set out to determine. 

Published in late 2021, a study that took place in Taiwan showed significant results. This study was retrospectively completed and looked at two and a half years between May 2016 and December 2018. Patients with type 2 diabetes taking SGLT-2 inhibitors were included, as well as a comparative group of patients taking a dipeptidyl peptidase 4 (DPP-4) inhibitor. Almost 48,000 patients on SGLT-2 inhibitors and over 180,000 patients on a DPP-4 inhibitor were included in this study. There were also over 47,000 pairs of patients that were using an SGLT-2 inhibitor or a DPP-4 inhibitor in a 1:1 propensity score-matched analysis. This concluded to include over 231,000 patients, out of which approximately 114,000 were women and had a mean age of 61.5 years. 

SGLT-2 inhibitors included in this study were dapagliflozin, empagliflozin, and canagliflozin. The DPP-4 inhibitors medications were alogliptin, linagliptin, sitagliptin, saxagliptin, and vildagliptin. The primary outcome of this study was the incidence of gout. Determination of gout was established by using the diagnostic codes from ICD-9-CM and ICD-10-CM. This study had many strengths and limitations. The study had a large sample size with a nationwide reach. Another strength of this study was that patients with previous gout diagnoses and those who used gout-related medications were excluded in this trial, preventing any overlap for outcomes. The study did note a few limitations. These included the late introduction of SGLT-2 inhibitors to Taiwan, the medications were not introduced until 2016. This made the study group smaller and lessened the power. Other limitations were the limited time frame of outcomes and observation. Also, detailed laboratory values were not available in the database used for collection, possibly influencing the study outcomes. 

This study’s results may begin to pave the way for the use of SGLT-2 inhibitors to prevent gout occurrence. Overall, the gout incidence was 20.26 per 1000 patient-years for SGLT-2 inhibitors and 24.3 per 1000 patient-years for DPP-4 inhibitors. The study team adjusted the risk factors in the propensity score-matched population. It was found that the SGLT-2 inhibitors were associated with a lower incidence of gout when compared to the DPP-4 inhibitors. This was especially true in patients taking dapagliflozin. The researchers included different subgroups of comorbidities in this study. These comorbidities included high blood pressure, high cholesterol, cerebral vascular disease, coronary artery disease, obesity, and chronic kidney disease (CKD). A subgroup analysis was completed and found that although SGLT-2 inhibitors showed benefit in type 2 diabetes achieving a lesser gout rate, there was no difference among the different comorbidities. 

In one US study, the researchers indicated a notable decrease of 30% in gout risk. The difference between this study and the previously discussed is the combined use of an SGLT-2 inhibitor and a glucagon-like peptide (GLP-1) agonist. The significant difference between the two studies could be that GLP-1 agonists alone do not influence the blood urate levels.

What does this mean for future treatment plans? Patients with type 2 diabetes and common comorbidities at high risk for gout attacks could be placed on an SGLT-2 inhibitor if tolerated. However, an easier way to determine the risk for gout should be initiated to make the process more efficient. 

Practice Pearls

• Sodium-glucose transport protein two inhibitors are a staple in the treatment interventions of patients with type 2 diabetes. 
• Gout incidence decreased by 11% when patients were taking an SGLT-2 inhibitor compared to a DPP-4 inhibitor. This was especially true in patients taking dapagliflozin.
• Other studies showed even more decrease in gout incidence with different scenarios. 

Baranwal, Medha. “SGLT2 Inhibitors May Protect Type 2 Diabetes Patients from Gout: JAMA.” Medical Dialogues, Medical Dialogues, 22 Nov. 2021.

Chung, Mu-Chi, et al. “Association of Sodium-Glucose Transport Protein Inhibitor Use for Diabetes and Incidence of Gout.” JAMA Network Open, JAMA Network, 19 Nov. 2021,

Quinlynn Champ, PharmD Candidate 2022, South College School of Pharmacy