The study, published in January 2020 in the Annals of Internal Medicine, found that adults with type 2 diabetes who were prescribed an SGLT2 inhibitor (sodium-glucose co-transporter-2) had a lower rate of gout than those prescribed a GLP1 receptor agonist, another type 2 diabetes drug class. Invokana (canagliflozin), Farxiga (dapagliflozin), and Jardiance (empagliflozin) are examples of SGLT2 inhibitors. “In light of these results, clinicians may lean toward SGLT2 therapy when additional anti-hyperglycemic therapy is being initiated in patients with type 2 diabetes that have frequent flares of gout,” says Kevin M. Pantalone, DO, an endocrinologist at Twinsburg Family Health and Surgery Center in Ohio, and the director of diabetes initiatives in the department of endocrinology, diabetes, and metabolism at Cleveland Clinic. SGLT2 inhibitors work by keeping glucose from being absorbed in the kidneys; excess glucose is excreted through the urine, which keeps sugar levels in the blood down. Glucagon-like peptide (GLP1) agonists, also known as incretin mimetics, are also used to treat type 2 diabetes. These drugs copy the action of incretin, a hormone that helps the pancreas produce insulin after meals and helps keep blood sugar levels in the normal range. RELATED: What Are the Pros and Cons of SGLT2 Inhibitors for Type 2 Diabetes?
The Connection Between Gout and Type 2 Diabetes
An estimated eight million people in the United States have gout, according to the Alliance for Gout Awareness. Gout typically affects one joint at a time, with about 1 in 2 attacks beginning in the big toe joint. Gout is caused by hyperuricemia, which can happen when there is too much uric acid in the body. Uric acid can build up in the joints, fluids, and tissues, which can lead to gout, according to the Centers for Disease Control and Prevention (CDC). Risk factors for gout include being male, having obesity, and chronic conditions such as heart failure, high blood pressure, insulin resistance, metabolic syndrome, poor kidney function, and diabetes, according to the CDC. Sometimes the pain and symptoms of gout go away temporarily, called remission, but can return suddenly and last days or weeks. Other symptoms include swelling, redness, and heat. Although the condition can’t be cured, it can be effectively treated and managed through pain medication, and diet and lifestyle changes. According to the study authors, SGLT2 inhibitors are already known to reduce uric acid levels, but whether that leads to reducing gout risk is still unclear. To further illuminate the impact, investigators used information from a healthcare claims database that contained individual information on healthcare use, health condition diagnoses, tests and procedures, lab results, and prescriptions filled. RELATED: Do You Know the Risk Factors for Gout?
Why Researchers Compared SGLT2 Inhibitors and GLP1 Agonists
Through this data, researchers were able to identify which patients were newly prescribed an SGLT2 inhibitor or a GLP1 agonist. GLP1 agonists were chosen as the comparator because they’ve been shown to not have an effect on serum uric acid, according to researchers. Researchers excluded any participants who had a history of gout or received treatment for gout. Researchers then used what’s called a propensity score, which is often used in observational studies to make sure that the effects (or lack of effects) are due to the variable being studied. In this case, that variable is the medication for type 2 diabetes, and not another variable, such as age, smoking status, other chronic diseases, or other medication. After propensity score matching, the study included 239,060 people: 119,530 on an SGLT2 inhibitor and 119,530 on a GLP1 agonist. The average age of participants was 54. Also, 52 percent of the subjects were women, 2 out of 3 had high blood pressure, and about 25 percent had filled a prescription for insulin. Mean follow-up was 302 days for people prescribed the SGLT2 inhibitor and 261 days for those prescribed the GLP1 agonist. The analysis revealed that there was a nearly 40 percent relative risk reduction for people on the SGLT2 inhibitor compared with those on the GLP1 agonist. There were 4.9 incidences of gout per 1,000 persons compared with 7.8 cases per 1,000 persons in the GLP1 agonist group. These results suggest that people with type 2 diabetes who may be at an increased risk of gout because of family history, diet patterns, or other comorbidities may see more benefits from SGLT2 inhibitors than from other options, says Seoyoung Catherine Kim, ScD, MD, associate professor of medicine at Harvard Medical School in Boston and coauthor of the study. Dr. Kim advises that anyone who is interested in taking an SGLT2 inhibitor discuss the risks and side effects with their healthcare team. The suspected reason behind the lower gout incidence is that SGLT2 inhibitors reduce the glucose level in people with diabetes by increasing the amount of glucose that gets passed out in the urine, says Kim. “At the same time, the drugs also increase the amount of urate in the urine; thus, they can reduce the serum urate level as well,” says Kim. By getting rid of some of the excess urate through urinating, the likelihood of uric acid building up is also reduced. Uric acid buildup can lead to gout. That’s when sharp crystals form within a joint or surrounding tissue, causing inflammation, pain, and swelling, according to the CDC. SGLT2 inhibitors’ effect on reducing serum uric acid has been shown in previous research, including a meta-analysis published in February of 2018 in the journal Diabetes, Obesity, and Metabolism, notes Kim. RELATED: SGLT2 Inhibitors May Lower the Risk for Heart Disease, Study Shows
What Scientists Still Don’t Know About Diabetes Medication for Gout Prevention
Although this is a very interesting observation, further investigation is required, says Dr. Pantalone. “The study is a retrospective study that is hypothesis-generating; it cannot establish causality,” he says. “It is also possible that the converse is true — that GLP1 agonist therapy may be associated with an increased risk of developing gout versus that of SGLT2 inhibitor therapy,” says Pantalone. “It is important to note that clinical trials of the FDA [U.S. Food and Drug Administration]–approved SGLT2 inhibitor and GLP1 agonist therapies did not identify any imbalance in gout between these therapies versus the active comparators or placebo,” he adds. Kim says, “Our findings should be confirmed in future real-world studies or trials.” More studies that evaluate the effect of SGLT2 on reducing gout flares among patients with a known diagnosis of gout may be needed, she adds. In a study published in December 2019 in The Lancet Rheumatology, investigators found that canagliflozin, an SGLT2 inhibitor, reduced gout serum rate concentration and reduced events related to gout flare in people with type 2 diabetes when compared with placebo.
