Diabetes Drug Class Appears to Reduce Recurrent Gout Flares

Miriam E. Tucker

August 31, 2023

The glucose-lowering drug class sodium-glucose cotransporter-2 (SGLT2) inhibitors appear to reduce the risk for recurrent gout flares in people with gout and type 2 diabetes, and to lessen excess mortality in those individuals, compared with those who initiated other types of glucose-lowering medications, new data suggest.

Among nearly 6000 adults with both type 2 diabetes and gout from a United Kingdom primary care database, initiation of SGLT2 inhibitor treatment was associated with 19% fewer recurrent gout flares and 29% lower mortality.

Moreover, unlike other urate-lowering therapies, there were no apparent transient increases in the risk of gout flares after initiating therapy, Jie Wei, PhD, of Health Management Center, Xiangya Hospital, Central South University, Changsha, China, and colleagues report in JAMA Network Open,  published online August 25, 2023.

These results are important because current management of gout is suboptimal. Many patients either don’t receive adequate urate-lowering therapies such as allopurinol or stop taking them, Wei and colleagues say.

In addition to lowering glucose, SGLT2 inhibitors also reduce the risk for major adverse cardiovascular events and all-cause mortality in people regardless of their diabetes status. Previous studies have also found that SGLT2 inhibitors reduce the risk for developing gout and of gout flares.

Dr John FitzGerald

Asked to comment, gout specialist John D. FitzGerald, MD, PhD, clinical chief of rheumatology at the University of California, Los Angeles, told Medscape Medical News, "I think it’s a well-done paper, with a large dataset. I think it just reinforces the findings from the other papers. Mostly anything that lowers uric acid levels is going to lower recurrent gout attacks, so it all makes sense."

However, while FitzGerald thinks the drug class is a good option for people with diabetes or cardiorenal indications for them who also have gout, he doesn’t envision it as first-line for most other patients with gout. "The current treatments are very effective. Allopurinol brings down uric acid levels by five to seven points. There are patients who fail allopurinol, but those are less than 5%."

The most common reason patients stop taking allopurinol is the frequent initial gout flare. But that’s preventable, FitzGerald said, either by titrating up slowly, or by adding colchicine along with it. "By going slowly, you can avoid that flare risk. I think that’s what’s going on with the SGLT2 inhibitor. It’s not a dramatic urate-lowering drug, but it is clinically meaningful. I think that’s what this paper is showing."

But, he noted, "I think there are so many reasons to start the SGLT2 inhibitors that if somebody also has gout, all the better. And, if somebody is on the margin with diabetes and gout control and can’t go with allopurinol, it would be great to add for both conditions."

Less Gout Recurrence, Lower Mortality

The retrospective study was conducted from January 1, 2013, to March 31, 2022. Among 5931 patients with both type 2 diabetes and gout, 1548 (26.1%) initiated an SGLT2 inhibitor (dapagliflozin, empagliflozin, or canagliflozin), while 4383 (73.9%) initiated treatment with other active comparators, mostly (92.6%) dipeptidyl peptidase-4 (DPP-4) inhibitors.

Gout flares were identified in the charts for a total of 86% of the participants. The weighted incidence rates for the first recurrent flare were 32.4 vs. 41.2 per 1000 person-years in the SGLT2 inhibitor vs comparator groups, with a weighted absolute rate difference of -8.8/1000 and weighted hazard ratio of 0.81, a significant difference.

All-cause mortality was 18.8 vs 24.9 per 1000 person-years, respectively, giving a hazard ratio of 0.71 at 5-year follow-up.

FitzGerald, who chaired the American College of Rheumatology’s 2020 gout guidelines, said he anticipates that the SGLT2 inhibitors will be mentioned in the next update to the ACR’s now "living" guidelines, although he was not speaking on the organization’s behalf for this article.

"We talk about losartan in the current [ACR guidelines], about its specific uric acid-lowering effect. Drugs can make uric acid worse or better. For example, thiazides make it higher. I think the SGLT2 [inhibitors] are important, but I don’t think they’re huge. The study is great, and I think the drugs are great, but I don’t think they will change the way gout is managed."

This work was supported by grants from the National Key Research and Development Plan, the National Natural Science Foundation of China, the Project Program of National Clinical Research Center for Geriatric Disorders, and from the Natural Science Foundation of Hunan Province. Wei reported receiving grant funding from Xiangya Hospital Central South University Project Program of National Clinical Research Center for Geriatric Disorders and the Science and Technology Department of Hunan Province, the Natural Science Foundation of Hunan Province, during the conduct of the study. FitzGerald reports no relevant financial relationships.

JAMA Network Open. Published online August 25, 2023. Full text.

Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape, with other work appearing in The Washington Post, NPR’s Shots blog, and Diabetes Forecast magazine. She is on X, formerly known as Twitter, @MiriamETucker.

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