Research Award Recipients

Adding AcetazolamIde on toP of SGLT2 inhibition in TyPe 2 DiabEtes and AlbuminuRia - The DIPPER Pilot study

Co-applicant(s): Adeera Levin, Ayodele Odutayo, Bruce Perkins, James Bowers, Kim Connelly, Leif Erik Lovblom, Luxcia Kugathasan, Massimo Nardone, Patricia Pace, Rowena Tulio, Vikas Srinivasan Sridhar

Lay Abstract

Background: Nearly 1 in 2 Canadians living with type 2 diabetes (T2D) also have kidney disease. The development of kidney disease significantly limits patient quality and quantity of life, and places a large burden on the healthcare system. Current treatments can help slow down kidney damage, but do not fully target the root cause of the disease. Our research focuses on one early cause of kidney damage called hyperfiltration – this is when the kidneys work too hard and filter blood too quickly. Overtime, this leads to high blood pressure within the kidneys' delicate filtering units, causing protein leakage into the urine and loss of kidney function. A reduction in hyperfiltration can be demonstrated by a short term and reversible reduction in kidney function.

Purpose: Our study will test whether a low-cost drug called acetazolamide can reduce hyperfiltration and prevention kidney damage. Acetazolamide works by changing how the kidneys handle sodium, which may help reduce hyperfiltration. We are especially interested in how acetazolamide might work alongside dapagliflozin, a medication class already approved for people with T2D and known to protect the kidneys. Dapagliflozin also changes how the kidneys handle sodium and lowers hyperfiltration, but through a different target.

Method: We propose a 16-week study in people with T2D and early signs of kidney disease to test how three different doses of acetazolamide affect hyperfiltration when added to ongoing treatment with dapagliflozin. Before starting the dosing part of the study, participants will take dapagliflozin alone for 4 weeks to establish a stable starting point for the rest of the study. Subsequently, participants treated with dapagliflozin will receive gradually increasing doses of acetazolamide. Each dose will be taken for 2 weeks followed by a 2-week break where they will continue taking dapagliflozin but stop acetazolamide. We are interested in learning how different doses of acetazolamide added to dapagliflozin affects kidney function and hyperfiltration. We plan to recruit a total of 20 patients with T2D and kidney disease from Toronto General Hospital, St. Paul’s Hospital, and Vancouver General Hospital.

Anticipated Outcomes: We anticipate that acetazolamide will reduce hyperfiltration. This information will help us design a larger trial in the future by identifying the most appropriate dose of acetazolamide to use and estimating how many participants we will need to detect a meaningful change in kidney function.

Patient Engagement: We are working closely with our patient partners who have lived experience with diabetes and kidney disease. From the start, they helped shape the study by advising on visit schedules, communication materials, and the overall focus of the research. Their voices helped us ensure this study reflects real-world priorities and concerns. Our patient partners will also help us explain the results in clear, meaningful ways – like creating videos, infographics, and handouts – so that the information is accessible and useful to other patients, families, and communities.

Relevance to Patients/Community: Cost is a major barrier to care. Many drugs for kidney disease cost thousands of dollars each year and may not be fully covered by insurance. Our patient partners have described this financial strain as overwhelming, stating that “we just want something that works and is affordable”. Acetazolamide is off-patent and, if proven to be effective alongside current therapies, offers an inexpensive new therapy to protect kidney function. Our research addresses not just a medical gap, but a social one: making kidney care more accessible for everyone, not just those who can afford expensive medications.

Conclusion: This study will be the first to explore acetazolamide on top of dapagliflozin in people with T2D. If acetazolamide proves effective, it could offer a new, affordable treatment option for people with T2D to prevent the development of kidney failure. This could help protect kidney function, reduce the need for costly treatments, and ease pressure on healthcare systems. In the long run, this study has the potential to improve the health and well-being of many people living with kidney disease and diabetes.