SGLT2 Inhibitors May Benefit Patients with Kidney and Cardiovascular Disease

Older Classes of Diabetes Drugs May Find New Uses

Empagliflozin Diabetes Drug Molecule
Empagliflozin Diabetes Drug Molecule

Some classes of diabetes drugs may offer benefits to patients with kidney and cardiovascular disease but are rarely prescribed to treat patients with these conditions in which they could be most effective. In some cases, warnings or contraindications that are no longer relevant to the patients’ conditions may limit use.


Daniel Edmonston, MD, a Duke nephrology fellow who has studied the latest research involving classes of diabetes medications, says the potential uses and benefits of two sodium-glucose cotransporter-2 (SGLT2) inhibitors used to treat type 2 diabetes mellitus (T2DM)—canagliflozin and empagliflozin—may mirror the acceptance of statins: slow initial adoption followed by broad acceptance.


Edmonston cites recent evidence showing that canagliflozin used to treat patients with T2DM also provides significant cardiovascular protection by reducing the risk for heart attack and heart failure. Similar results were reported from a safety trial of empagliflozin during which researchers discovered a decreased risk for heart attacks. The trial also had most promising results for patients with renal conditions; patients with T2DM who were administered empagliflozin demonstrated promising results for renal outcomes.


“When reviewing the latest research, the biggest point of emphasis for physicians practicing outside academic medicine is the strikingly low adoption rate of some of the more novel applications of these medications despite very promising results in recent research,” he says.


Recent research highlights the effectiveness of these SGLT2 inhibitors for the prevention of major adverse cardiovascular events and improved renal outcomes independent of glycemic control. Although the majority of subjects in the study had relatively normal kidney function, the study included participants with moderate chronic kidney disease (estimated glomerular filtration rate >30 ml/min/1.73m2). In a subanalysis of the EMPA-REG OUTCOME trial, researchers found that baseline renal function did not alter the improved clinical outcomes, including mortality, seen with treatment with empagliflozin.


Potential outcomes for patients with cardiovascular and renal conditions may be comparable to the gradual acceptance of statins, Edmonston says. Early adoption for statins was slow, but now they are prescribed widely as valuable, life-time therapies for uses beyond their impact on cholesterol.


Patients with diabetes generally experience a steady decline in kidney function. Most current therapies simply delay that decline, but the 2 SGLT2 inhibitors appear to offer a strategy to slow the decline more significantly. Still, Edmonston cautions, patients with advanced kidney disease or acute kidney injury should not be treated with empagliflozin or canagliflozin until additional research is completed.


But the growing use of drugs developed for diabetes to treat both cardiovascular and renal conditions offers long-term promise, he says. “It’s exciting to follow the results of these new trials as the research expands to more patients, such as those with heart failure who do not have diabetes.”