Reduced gout incidence with SGLT-2 inhibitors vs GLP-1 receptor agonists

Individuals with type 2 diabetes (T2D) who are prescribed an SGLT2* inhibitor may have a reduced risk for developing gout compared with those who are prescribed a GLP-1** receptor agonist, according to a study from the US.

Using a US commercial insurance database, the researchers identified 295,907 adults (mean age 54 years, 52 percent female) with T2D who were newly prescribed either an SGLT-2 inhibitor or a GLP-1 receptor agonist between March 2013 and December 2017 (n=119,530 patients in each group after propensity score matching). Patients were followed up for a mean 302 (SGLT-2 inhibitors) and 261 (GLP-1 receptor agonists) days, respectively.

Incidence of gout was lower among patients with T2D who received an SGLT-2 inhibitor compared with those who received a GLP-1 receptor agonist (4.9 vs 7.8 per 1,000 person-years; adjusted hazard ratio [adjHR], 0.64, 95 percent confidence interval [CI], 0.57–0.72). [Ann Intern Med 2020;doi:10.7326/M19-2610]

The reduced incidence with SGLT-2 inhibitors vs GLP-1 receptor agonists was consistent regardless of sex (adjHR, 0.69 and 0.57 in men and women, respectively), age (adjHR, 0.64 and 0.67 in individuals aged ≤60 and >60 years, respectively), and baseline diuretic use (adjHR, 0.45 and 0.74 in users and non-users, respectively).

There was also a reduced risk of heart failure hospitalizations in patients prescribed an SGLT-2 inhibitor compared with those prescribed a GLP-1 receptor agonist (1.7 vs 2.7 per 1,000 person-years; adjHR, 0.63, 95 percent CI, 0.51–0.77).

When compared with new users of DPP4*** inhibitors in a sensitivity analysis (n=97,442 in each group), gout incidence was still lower among SGLT-2 inhibitor users (5.35 vs 8.08 per 1,000 person-years; adjHR, 0.66, 95 percent CI, 0.58–0.75).

The researchers pointed out a recent meta-analysis of 62 studies that demonstrated a reduction in serum uric acid levels following SGLT-2 inhibitor use. [Diabetes Obes Metab 2018;20:458-462] However, many of the studies included in the meta-analysis comprised patient populations without hyperuricaemia at baseline, and as such, the clinical relevance of this reduction in uric acid levels was unclear, they said.

Furthermore, GLP-1 receptor agonists are not known to reduce uric acid levels, [Diabetes Obes Metab 2018;20:1235-1245] making them the “ideal comparator” to assess if this effect of SGLT-2 inhibitors translates to a reduction in gout risk.

“Logically, patients with hyperuricaemia and higher serum uric acid levels at baseline have a greater potential for reducing uric acid levels. If proven, this will be relevant for adults with diabetes who also have hyperuricaemia, and one day may also be relevant for adults with hyperuricaemia who do not have diabetes,” the researchers said.

Aside from the need for additional research to confirm the gout-reducing characteristics of SGLT-2 inhibitors, the researchers recommended studies to assess this outcome in individuals with or at high-risk for developing gout. 

With a recent study showing an elevated risk of cardiovascular and all-cause mortality with the gout treatment febuxostat, [N Engl J Med 2018;378:1200-1210], there is an increased need to identify new treatments for this condition, they added.

“If SGLT-2 inhibitors are found to lower the risk for gout, they may be the ideal treatment for patients with diabetes who are at high risk for gout, because SGLT-2 inhibitors also reduce the risk for cardiovascular mortality and, potentially, all-cause mortality,” they said.