Canadian Study: SGLT2 Inhibitors Cut Potassium Risk in Diabetics

Canadian Research Shows SGLT2 Inhibitors Help Protect Against a Dangerous Side Effect of Common Blood Pressure Drugs

A study from Canada has uncovered an important benefit of a widely used class of diabetes medications — one that could directly influence how American doctors manage patients juggling multiple serious conditions at once.

Researchers at St. Michael's Hospital in Toronto analyzed real-world data from over 40,000 Ontario residents aged 66 and older who were taking medications known as RAAS inhibitors (RAASi) — a broad category that includes common blood pressure and kidney-protecting drugs like lisinopril, losartan, and spironolactone. These medications are essential for many people with diabetes, heart failure, or chronic kidney disease (CKD), but they carry a well-known risk: they can cause hyperkalemia, a dangerous buildup of potassium in the blood.

What the Researchers Found

The Canadian team tracked whether starting an SGLT2 inhibitor — a diabetes drug class that includes empagliflozin (Jardiance), dapagliflozin (Farxiga), and canagliflozin (Invokana) — changed the risk of developing hyperkalemia. Hyperkalemia was defined as a serum potassium level above 5.5 mEq/L (the same threshold used in US clinical practice), confirmed either by lab test or a documented medical encounter.

The results were notable: patients who started an SGLT2 inhibitor had an 11% lower risk of developing hyperkalemia (hazard ratio 0.89, 95% CI 0.82–0.96) compared to those who did not. Equally important, SGLT2 inhibitor users were far less likely to have their blood pressure medication discontinued — 36% vs. 45% — meaning more patients were able to stay on their heart- and kidney-protective medications.

The study population closely mirrors patients seen in US clinics: 95% had diabetes, 32% had moderate-to-severe CKD (stages 3–5), and 17% had heart failure — conditions that frequently overlap and demand careful medication management.

Why an International Perspective Matters

Canada's publicly funded healthcare system in Ontario enabled researchers to track a large, diverse population over six years (2015–2021) using real-world administrative and lab data. This type of large-scale population study is harder to conduct in the fragmented US healthcare system, making Canadian findings especially valuable for confirming whether clinical trial results hold up in everyday practice — and they do.

How This Compares to US Guidelines

Current American Diabetes Association (ADA) guidelines already recommend SGLT2 inhibitors for patients with type 2 diabetes who also have CKD or heart failure. However, hyperkalemia risk from RAASi is a real barrier that sometimes causes doctors to reduce or stop these protective medications. This study suggests that adding an SGLT2 inhibitor may actually help preserve the ability to stay on RAASi therapy — a nuance not yet fully emphasized in US prescribing guidance.

Why This Matters for US Patients

If you have diabetes and also take a blood pressure or kidney-protecting medication like an ACE inhibitor or ARB, high potassium levels may be a concern your doctor has raised. This Canadian research — conducted in the real world, not just a controlled trial — suggests that adding an SGLT2 inhibitor to your regimen may reduce that risk while helping you stay on the medications your heart and kidneys depend on. Talk to your doctor about whether an SGLT2 inhibitor is appropriate for your situation, especially if you have CKD or heart failure alongside diabetes.

Study Citation

Wing, Ray, Yau. SGLT2 Inhibitors and Risk for Hyperkalemia Among Individuals Receiving RAAS Inhibitors. JAMA Internal Medicine, 2025. DOI: 10.1001/jamainternmed.2025.0686. PMID: 40293730.