New Hope for Treating Chronic Kidney Disease in Type 1 Diabetes
By Michael Howerton
New research is sorely needed to test therapies for chronic kidney disease for those with type 1 diabetes, such as there is for type 2 diabetes. Researchers at EASD 2023 pointed to a new study, FINE-ONE, which will be recruiting in coming months and promises to add new data to the quest.
Treatments for chronic kidney disease (CKD) have increasingly become available for those with type 2 diabetes. Most recently, the SGLT-2 inhibitor Jardiance (empagliflozin) was approved to treat CKD in adults with or without type 2 diabetes. Despite the fact that people with type 1 diabetes are more likely to encounter dangerous kidney complications, medications for CKD have remained frustratingly not FDA approved for those with type 1 diabetes.
Now, with new research exploring this urgent need, that could soon change. A panel at EASD 2023 in Hamburg, Germany, explored this urgent need to begin more clinical trials to find ways to safely bring these treatments to those with type 1 diabetes, calling for more studies and highlighting the FINE-ONE trial, which is set to begin in the coming months.
Historically, there have been few clinical trials testing medications for CKD in type 1 diabetes
The problem has long been the absence of enough clinical trials testing these drugs in the type 1 diabetes population, which has been considerably harder to study for renal damage and failure. Many drugs approved for type 2 diabetes – include SGLT-2 inhibitors and GLP-1 receptor agonists, as well as finerenone (sold under the name Kerendia) – lower glucose levels and also protect kidney and cardiovascular health.
In addition to the lack of clinical trials, the fear that these medications could dangerously lower glucose levels and result in hypoglycemia, and perhaps even cause euglycemic DKA (EDKA), has hampered research.
Recognizing the possibility of hypoglycemia and EDKA, caution is warranted, such as perhaps requiring continuous glucose monitors (CGM) to protect against dangerous lows. Ultimately, researchers maintained that this population deserves trials to explore access to these treatments that hold such potential to improve and save lives.
Dr. Kathleen Tuttle of the University of Washington presented a sophisticated algorithm using electronic health records to better identify patients with type 1 diabetes and CKD. She also emphasized the increased risk of both kidney and heart disease in type 1 diabetes.
There is a critical need for more research and large scale studies, Tuttle said, citing the overall prevalence of CKD in those with type 1 diabetes of nearly 30%.
Furthermore, Tuttle said, kidney complications increase with age, with CKD affecting 38% of those with type 1 over 60 years old, and at more than 70% for those over 80 years. More than half of all people with type 1 diabetes have stage 3 CKD and, disturbingly, more than 1 in 5 overall have kidney failure, likely requiring dialysis or a transplant.
FINE-ONE trial to investigate finerenone in type 1 diabetes
Dr. Hiddo Lambers Heerspink, professor of clinical trials and personalized medicine at University Medical Center Groningen, Netherlands, detailed the alarming rates of severe albuminuria progressing to kidney failure and mortality among the type 1 population in recent decades.
Given that it has been 30 years since the last trial investigating new treatment for kidney disease in those with type 1, it is high time for more attention, research and innovation in this area, Heerspink said. The last trial in type 1 diabetes was for the ACE inhibitor captopril (sold under the brand name Capoten) in 1993, while there have been numerous studies since then looking at CKD in those with type 2 diabetes.
But that is about to change with the launch of Bayer’s FINE-ONE trial, the first in decades to test a medication to treat CKD in type 1 diabetes.
“Few therapeutic options are available for patients with type 1 diabetes and CKD despite the high risk of morbidity and mortality,” Heerspink said. “FINE-ONE is the first trial in 30 years that seeks an indication for the treatment of type 1 diabetes and CKD.”
The new trial, which is expected to begin recruiting adults with type 1 early in 2024, uses change in albuminuria as a “bridging biomarker to translate the evidence for kidney protection with finerenone from type 2 to type 1 diabetes,” he said. The trial will also evaluate the safety of the drug in people with type 1 diabetes.
The kidney protective effects of finerenone in type 2 diabetes are almost completely explained by finerenone’s ability to reduce albuminuria, protein in the urine, Heerspink said. The role of albuminuria in the progression of CKD is similar in both types of diabetes.
Although FINE-ONE is a great start, more research is needed, including with GLP-1 receptor agonists like semaglutide and tirzepatide. Indeed, an analysis presented at EASD 2022 showed that tirzepatide may protect against kidney disease. These drugs are needed not only to lower glucose but also for their benefits in preventing and treating kidney and heart disease.
