Researchers at UHN’s Toronto General Hospital Research Institute have found that a class of diabetes medications, including dapagliflozin — used with diet and exercise to lower blood sugar in adults with Type 2 diabetes — is associated with reducing risk factors linked with cardiovascular disease and end-stage kidney disease (ESKD) in patients with Type 1 diabetes (T1D).
People with T1D have an increased risk of cardiovascular disease and kidney failure. They are 10 times to 30 times more likely to develop kidney failure compared to the general population.
Additionally, a diagnosis of T1D before the age of 10 can lead to a threefold increase in the risk of heart disease.
Thus, identifying therapies to help reduce these risks is essential.
Sodium-glucose cotransporter-2 (SGLT2) inhibitors, a class of drugs that includes dapagliflozin, have been shown to lower these risks in people with Type 2 diabetes and in people with kidney and cardiovascular disease associated with other conditions.
However, no major studies have confirmed similar benefits for people with T1D.
To investigate this, the research team conducted a post hoc analysis of previous clinical trial data from the DEPICT-1 and DEPICT-2 studies. These trials were multicentre, phase 3, randomized studies that evaluated the safety and efficacy of dapagliflozin as an add-on therapy to insulin in lowering blood sugar levels.
The researchers used two risk prediction models to estimate changes in the 10-year cardiovascular disease risk and five-year ESKD risk in 1,473 participants with T1D who took dapagliflozin.
After 24 weeks of treatment, participants taking dapagliflozin had an approximately six per cent lower estimated risk of cardiovascular disease, as determined by one risk model, and a nine per cent lower risk, as determined by another, compared to those taking a placebo. Additionally, dapagliflozin lowered the risk of ESKD by approximately eight per cent compared to the placebo after 52 weeks of treatment.
The benefits on kidney health were especially pronounced in participants with chronic kidney disease (CKD).
These findings suggest that SGLT2 inhibitors like dapagliflozin could play an important role in protecting the heart and kidneys in people with T1D.
The authors have also been able to show similar potential benefits in separate models with another SGLT2 inhibitor called empagliflozin, which was used in the EASE clinical trials, and have published this work in the journal Diabetes Care. This study found that participants with T1D with the highest cardiovascular risk at the beginning of the trial may particularly benefit from these therapies.
Together, the study authors emphasize the need for dedicated clinical trials to confirm these benefits.
As part of this effort, the team has initiated a new trial called “SUGARNSALT,” funded by the Canadian Institutes of Health Research, the Kidney Foundation of Canada, and Breakthrough-T1D, which will determine if there are long-term kidney benefits in this unique patient population.
If proven effective, these medications could help individuals with T1D reduce their risk of life-threatening complications.
The first author of the study published in CJASN is Dr. Massimo Nardone, postdoctoral researcher at Toronto General Hospital Research Institute. The co-first authors of the study published in Diabetes Care are Luxcia Kugathasan, PhD candidate at the University of Toronto (U of T) and Toronto General Hospital Research Institute, and Dr. Pritha Dutta, postdoctoral researcher at the University of Waterloo. The senior author of both studies is Dr. David Cherney, Senior Scientist at Toronto General Hospital Research Institute and a professor in the Department of Medicine at U of T.
This study was supported by generous donors to UHN Foundation.
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