Canada Study: Adding Empagliflozin to Closed-Loop Insulin Pumps Improves Blood Sugar Control in Type 1 Diabetes

A study from Canada has found that combining the SGLT2 inhibitor empagliflozin with automated closed-loop insulin delivery systems significantly improves blood sugar control in adults with type 1 diabetes — though the combination also raises an important safety flag that every patient and clinician should understand before considering this approach.

What International Perspective Does This Bring to US Patients?

Canada's universal healthcare system allows researchers at institutions like McGill University in Montreal to conduct tightly controlled trials with consistent medication access and follow-up — conditions that can be harder to replicate in fragmented US healthcare settings. This Canadian trial used a rigorous 2×2 factorial crossover design, meaning the same participants experienced all four treatment combinations, giving the results unusually high reliability. For American patients already using or considering closed-loop systems like the Omnipod 5 or Tandem Control-IQ, this research speaks directly to a real and growing question: can adding an oral medication make these already-advanced devices work even better?

What the Study Found

Researchers at McGill University enrolled 27 adults with type 1 diabetes and tested four combinations over four weeks each: closed-loop insulin delivery alone, closed-loop plus empagliflozin 25 mg daily, sensor-augmented pump (SAP) therapy alone, and SAP plus empagliflozin. Twenty-four participants completed the full analysis.

The primary goal was improving time in range (TIR) — the percentage of the day blood glucose stays between 70–180 mg/dL (converted from the Canadian measure of 3.9–10.0 mmol/L, which is the same standard used in US guidelines from the American Diabetes Association).

Key results:

• Empagliflozin added to closed-loop therapy improved TIR by 7.2% compared to closed-loop alone
• Empagliflozin added to SAP therapy improved TIR by 11.4% compared to SAP alone
• The biggest gain came from the full combination: closed-loop plus empagliflozin improved TIR by 17.5% compared to SAP therapy with placebo
• No severe hypoglycemia or diabetic ketoacidosis (DKA) occurred in any treatment arm
• However, uncomplicated ketosis (elevated ketones without full DKA) was significantly more common when participants took empagliflozin

How This Compares to US Guidelines

The ADA currently does not recommend SGLT2 inhibitors as standard add-on therapy for type 1 diabetes, largely due to DKA risk. Empagliflozin is FDA-approved only for type 2 diabetes and heart failure indications. This Canadian trial adds to a growing body of evidence suggesting the benefit-risk balance may be favorable under careful monitoring, but US patients should not add empagliflozin to their regimen without explicit physician guidance.

Why This Matters for US Patients

Hundreds of thousands of Americans with type 1 diabetes use closed-loop insulin delivery systems, and many struggle to hit the ADA's recommended TIR target of over 70%. A nearly 17.5% improvement in TIR is clinically meaningful — that translates to roughly 2.5 additional hours per day spent in a healthy blood sugar range. However, the increased ketosis risk means this combination requires regular ketone monitoring, something US patients and their care teams must plan for proactively. This research supports ongoing conversations with your endocrinologist about whether off-label empagliflozin use might be appropriate for your specific situation.

Original Study

Authors: Haidar, Lovblom, Cardinez et al.
Journal: Nature Medicine (2022)
PMID: 35551290
DOI: 10.1038/s41591-022-01805-3