SLGT2 inhibitors work differently from other medicines used to control blood glucose. “SGLT2 inhibitors are a newer class of type 2 diabetes medication that reduce blood sugar by increasing the amount of sugar that is eliminated by the body through the urine,” says Silvio Inzucchi, MD, an endrocrinologist and professor at Yale School of Medicine in New Haven, Connecticut. This reduces blood glucose, and can play a role in improving your A1C, the two- to three-month average of your blood sugar levels that can indicate how well diabetes is being managed.
Farxiga (dapagliflozin)Invokana (canagliflozin)Jardiance (empagliflozin)Steglatro (ertugliflozin)Steglujan (ertugliflozin and sitagliptin)
Yet as with any prescription drugs, SGLT2 inhibitors carry certain risks, including infection, the FDA points out. “Lowering blood sugar in and of itself is important in that it helps to prevent some of the complications of diabetes, particularly eye disease and kidney disease, and peripheral nerve disease,” says Stephen D. Wiviott, MD, a cardiologist at Brigham and Women’s Hospital in Boston and associate professor of medicine at Harvard Medical School. “More recently, some classes of drugs, and SGLT2 inhibitors in particular, have demonstrated favorable effects on the heart and the progression of kidney disease as well.” RELATED: A Complete Guide to Type 2 Diabetes Treatment
SGLT2 Inhibitors Improve Heart Health in Many Ways
“The big news in recent years has been the cardiovascular benefits that go with these medications,” says Evan Sisson, PharmD, CDCES, a pharmacist and professor at Virginia Commonwealth University in Richmond. Heart disease is the leading cause of death for people with diabetes, notes the CDC, so drugs that can both lower blood glucose and preserve heart health are critical, experts say. “Several large studies have shown that several [SGLT2 inhibitors] reduce the risk of cardiac problems, especially being hospitalized from heart failure,” says Dr. Inzucchi. “They also appear to slow down the development of kidney problems. People at risk for these conditions appear to benefit the most.” First, SGLT2 inhibitors may help people with type 2 diabetes who already have heart disease, according to an empagliflozin study published in November 2015 in The New England Journal of Medicine (NEJM) and a canagliflozin study published in August 2017 in NEJM. Both studies suggested the drugs may reduce the likelihood of having another heart attack, stroke, or dying from heart disease. The American Diabetes Association’s (ADA) guidelines, published in January 2020 in the journal Diabetes Care, recommend SGLT2 inhibitors for people with diabetes who have been diagnosed with heart disease or who are at high risk for heart disease. Second, a January 2019 study in NEJM suggested that the SGLT2 inhibitor dapagliflozin helps people with diabetes from being hospitalized for heart failure, regardless of whether they had heart disease in the past or not, says Dr. Wiviott. Third, a November 2019 study in NEJM and the aforementioned March 2020 study in JAMA showed the cardiovascular benefits of dapagliflozin in people with heart failure regardless of whether they had diabetes. In other words, the medication helps the heart independent of lowering blood glucose. Why so much focus on the heart? In 2008, the FDA ensured that all diabetes drugs undergo studies to show their heart safety, says Daniel Hsia, MD, assistant professor at Louisiana State University’s Pennington Biomedical Research Center in Baton Rouge. Since then, research into SGLT2 inhibitors and another class of drugs called GLP1 agonists, including liraglutide and semaglutide, has shown no heart harm — and some heart rewards, according to one study published in July 2016 in NEJM and another study, published in November 2016 in NEJM. RELATED: Canagliflozin, an SGLT2 Inhibitor, Lowers Blood Sugar and Improves Heart Health
Why SGLT2 Inhibitors May Increase Your Risk for Urinary Tract Infections
Remember how SGLT2 inhibitors increase glucose in your urine so that it can be expelled from the body, thereby lowering blood sugar? Well, excess sugar in your urine creates a cozy environment for bacteria and fungi to thrive in your urinary tract or genital area. People with diabetes are already at high risk for these infections, says Dr. Hsia. “The incidence of urinary tract infections is about 50 percent greater in people with diabetes compared with people without diabetes,” he says. “Genital infections are 2 to 3 times more likely to occur in people with diabetes compared with those without diabetes," says Hsia. Wiviott says that there is a risk for genital infections for both men and women taking SGLT2 inhibitors, and these infections tend to be mild and easily treated with antibiotics. Tell your doctor if you have a history of these infections. Inzucchi says people taking SLGT2 inhibitors may notice that they urinate more frequently. Another more serious but extremely rare form of infection has been reported in people taking SGLT2 inhibitors, called Fournier’s gangrene, in which bacteria infect the underlying layers of skin of the genitals. A June 2019 study in the Annals of Internal Medicine reported that the FDA identified 55 cases of Fournier’s gangrene in people taking SGLT2 inhibitors between 2013 and 2019. The FDA notes that roughly 1.7 million patients filled prescriptions for SGLT2 inhibitors in 2017. It also recommends that individuals get attention immediately if they have symptoms of tenderness, redness, or swelling in their genital area. “These symptoms can worsen quickly, so it is important to seek treatment right away, as it can be a life-threatening bacterial infection,” says Hsia. Hsia points out that any and all drugs have risks, and that the risks of SGLT2 inhibitors must be balanced against their dual potential benefits for blood glucose and the heart. The SGLT2 inhibitor canagliflozin carries a warning for increased risk of amputations, and the FDA has also warned about diabetic ketoacidosis (DKA), a serious and sometimes deadly condition in which high blood glucose, called hyperglycemia, over a long period of time causes a buildup of toxic ketones in the blood. In rare cases, SGLT2s can cause euglycemic DKA, a buildup of ketones in the blood even with normal blood sugar levels, meaning this health emergency doesn’t only occur with hyperglycemia, noted an article published in September 2015 in the journal Diabetes Care. Dr. Sisson says SGLT2 inhibitors can also increase the risk for dehydration, especially in the summertime.
Who May Benefit From Taking SGLT2 Inhibitors — and Why
SGLT2 inhibitors may provide a unique advantage for people with type 2 diabetes with heart disease or kidney disease, says Inzucchi. These drugs have additional benefits to reduce blood pressure and body weight. People with diabetes should discuss the risks and benefits of these medications with their doctor, he adds. As for diabetes prevention, research hasn’t yet proved this benefit, nor has the FDA approved these drugs for this purpose. However, emerging research may warrant further study in this area. For example, at the ADA 2020 Scientific Sessions meeting in June, Inzucchi and his colleagues reported preliminary results that suggested people taking dapagliflozin were less likely to develop type 2 diabetes — the SGLT2 inhibitor reduced new-onset diabetes by 32 percent. Inzucchi reinforced the need for further study and FDA approval for this reason. In any case, Sisson and Wiviott both say these new drugs can cause providers to think beyond their specialties of cardiology or endocrinology. Good communication between different members of your healthcare team, including physicians, pharmacists, and diabetes educators, can help you choose the best medication, says Sisson. You might ask your team: Which medication gives the biggest bang for my buck? As a pharmacist and diabetes educator with the American Association of Diabetes Educators, Sisson points out the value of taking fewer medicines to cut costs and improve the likelihood that people stick to their medication regimen.
