SGLT2 inhibitors were linked with fewer flares and longer life than comparator antihyperglycaemics in patients with these conditions.
A large UK study has found that patients with type 2 diabetes and gout being treated with SGLT2 inhibitors were at lower risk of gout flares and all-cause mortality than comparable patients on GLP-1 receptor agonists or DPP-4 inhibitors.
The population-based retrospective cohort analysis reported a 19% lower rate of gout flares and 29% lower all-cause mortality in patients taking SGLT2 inhibitors versus the active comparators.
“These findings suggest that SGLT2i might hold potential in reducing the burden of recurrent gout flares and potentially narrowing the mortality gap between patients with gout and the general population,” wrote the authors in JAMA Network Open.
The study examined data from a UK general practice database and compared outcomes in almost 6000 patients with type 2 diabetes and gout initiating SGLT2 inhibitor treatment and those initiating GLP-1 receptor agonist or DPP-4 inhibitor treatment. The active comparators were chosen due to their neutral effect on serum urate levels in patients with diabetes.
There were around 1500 patients taking SGLT2 inhibitors, around 4000 on DPP4 inhibitors and around 300 on GLP-1 receptor agonists. Around 80% were male, the average age was 62, and most were overweight or obese.
The primary outcome was total number of recurrent gout flares, and the secondary outcomes were first recurrent gout flare and all-cause mortality over an average follow-up period of 2.7 years.
The incidence rate of recurrent gout flares was lower in the SGLT2 inhibitor group vs active comparators at 76.8 vs 99.0 per 1000 person-years respectively, a 21% reduced risk. The incidence rate of the first recurrent flare was 32.4 in the SGLT2 inhibitor group vs 41.2 in the comparator group, a 19% reduced risk.
While the mechanism for reduced gout flares associated with SGLT2 inhibitors was unclear and requires further research, one suggestion was that pumping glucose into urine also forces kidney urate elimination.
Meanwhile, the rate of all-cause mortality in the SGLT2 inhibitor group was 18.8 per 1000 person-years vs 24.9 in the comparator group, a 29% reduced risk. The lower risk was mainly seen in SGLT2 inhibitor initiators when compared to initiators of DDP-4 inhibitors rather than GLP-1 receptor agonists, although smaller numbers of patients taking GLP-1RA may have limited the statistical power.
The authors noted that SGLT2 inhibitors have known cardiovascular benefits and reduce all-cause mortality in people with and without diabetes. They have also been shown to reduce serum urate levels and reduce the risk of incident gout.
“However, to date, no study has specifically examined the association of SGLT2i with the risk of recurrent gout flares and all-cause mortality in patients with gout,” they wrote.
The study adds to findings from another recent large study involving 15,000 Canadian patients with type 2 diabetes and gout which found that patients on SGLT2 inhibitors had reduced risk of gout flares and myocardial infarction compared with those on DPP-4 inhibitors.
