SGLT2 Inhibitors Protect the Heart, New Study Reports

Sodium-glucose transport protein 2 (SGLT2) inhibitors are fairly new medications for the treatment of diabetes. The first to be approved by the U.S. Food and Drug Administration was Invokana (canagliflozin) in 2013, and since then three others have been added to the list: Farxiga (dapagliflozin), Jardiance (empagliflozin), and Steglatro (ertugliflozin). Also known as gliflozins, SGLT2 inhibitors prevent the reabsorption of sugar from the blood that passes through the kidneys. Increased excretion of blood sugar in urine means lower blood sugar levels.

The outlook for these medications has been encouraging. Not only have they been shown to help lower blood sugar levels, but studies have indicated they might also promote weight loss while lowering blood pressure levels. And more recently SGLT2 inhibitors have been linked to lower risk of stroke and heart attack. Now a new study has compared SGLT2 inhibitors to metformin, a common first-line treatment for diabetes. The study indicates that SGLT2 inhibitors are not only equally as effective as metformin in lowering the risk of stroke, death, and myocardial infarction (MI, more familiarly known as heart attack) but appear to be superior at managing heart failure.

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The study, which was published in the Annals of Internal Medicine, was conducted by researchers at Brigham and Women’s Hospital and Harvard Medical School in Boston. They obtained data on first-time diabetes medications from two databases — the Optum Clinformatics Data Mart and the IBM MarketScan. The population was made up of adults 18 and over with employer-sponsored health insurance or, for those 65 and above, a Medicare Advantage plan, who had been diagnosed with type 2 diabetes (T2D) but had not yet begun drug therapy. Of those in the study group, 8,613 were identified as first-time users of either canagliflozin, dapagliflozin, or empagliflozin, while 17,226 were identified as having begun taking metformin between April 2013 and March 2020.

After an average follow-up of one year, the researchers determined the risks for stroke and mortality were similar for SGLT2 inhibitor users and metformin users. However, the risk of hospitalization or death from heart failure was 20% less with those taking either canagliflozin, dapagliflozin, or empagliflozin compared to those taking metformin. The risk of heart attack among people taking SGLT2 inhibitors was slightly lower than among metformin users, but the difference was too slight to be considered statistically significant. The heart failure benefits of SGLT2 inhibitors compared to metformin first appeared after about six months, the authors reported. Another interesting finding was that SGLT2 inhibitor users had a slightly higher risk of genital infections, but otherwise safety reports were similar and the study authors said genital infections “may be less serious” than other safety outcomes, such as acute kidney injury, severe hypoglycemia (low blood sugar), and diabetic ketoacidosis (DKA), “and can be appropriately managed.” The findings of the new study were similar those from a large meta-analysis of cardiovascular outcome trials for canagliflozin, dapagliflozin, and empagliflozin in 2019 that reported “a statistically significant reduction in myocardial infarction risk in diabetic individuals treated with SGLT2 inhibitors.”

The new report might seem to indicate that doctors would want to favor SGLT2 inhibitors to metformin as initial therapy for their diabetes patients, but the authors weren’t ready to go that far. According to lead author HoJin Shin, BPharm, PhD, of the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital, “Our results suggest that SGLT-2i may be considered as first-line treatment for patients with T2D and cardiovascular disease or who are at increased risk for cardiovascular events. However, more evidence from randomized clinical trials or observational studies will help us to identify patients who would benefit most from using SGLT-2i as first-line Type 2 diabetes treatment.”

Want to learn more about SGLT2 inhibitors? Read “Diabetes Medicine: SGLT2 Inhibitors.”

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