Invokana Slows Down Kidney Disease Progression in People with Type 2 Diabetes

By Jeemin Kwon, Ann Carracher, Martin Kurian, Peter Rentzepis, and Kelly Close

Results from the CREDENCE trial suggest that Invokana’s kidney benefits exist on top of blood pressure lowering medications (standard of care)​

Results from CREDENCE show that people taking SGLT-2 inhibitor Invokana had 30% lower risk of end stage kidney disease, worsening kidney function, and kidney or heart-related death. The trial tested Invokana versus placebo (a “nothing” pill) in people with type 2 diabetes and chronic kidney disease (CKD). It was due to this exceedingly positive data that the trial was stopped early last year – it was deemed unethical to keep giving people placebo, given the clear kidney health benefit. The CREDENCE data was recently submitted to the FDA for approval to broaden Invokana’s recommended use to include the kidney benefits.

At baseline, study participants had an average A1C of 8.3% and all had either stage 2 or 3 CKD. Importantly, they were all on antihypertensive (blood pressure lowering) medications when tolerated, meaning the kidney health benefits exist on top of what standard-of-care CKD treatments already accomplish.

In addition to the kidney-protective benefits, results also confirmed Invokana’s heart health benefits compared to placebo:

• 31% lower risk of heart-related death or hospitalization for heart failure;
• 20% lower risk of heart attack, stroke, and heart-related death.

The FDA has already approved Invokana for heart-protective benefits in people with type 2 diabetes and heart disease, which is covered in detail here. 

At the end of the trial, there were also differences in body weight: on average, those on Invokana lost 4.4 pounds (2 kg) whereas those on placebo lost 2.4 pounds (1.1 kg). Researchers intentionally allowed participants to stay on other treatments for blood sugar management, so there was no significant difference between A1C levels between the Invokana and placebo group.  

Notably, there was no substantial difference in frequency of amputations between the Invokana and placebo groups. Both groups had an amputation rate of about 1% per year (every year, one out of 100 participants underwent an amputation). Given the increased amputation rate seen in a previous trial with Invokana, CANVAS, these results are very reassuring.

SGLT-2 inhibitors represent the first innovation in CKD treatments in 20 years. Dr. Carol Wysham of the University of Washington noted, “I eagerly awaited this data for two reasons: there is a huge unmet need for treatments to prevent progression of diabetes-related kidney disease. I also was relieved to see that the safety signals failed to demonstrate increase in amputations or fractures.” Dr. Daniel Drucker of the Lunenfled-Tanenbaum Research Institute added, “These results are transformative for the field and further enable personalized diabetes medicine to prevent kidney complications, improve heart health outcomes, and save lives for people with type 2 diabetes.” When announced at the World Congress of Nephrology in Australia, the results were met with enthusastic applause (see video here) – it is quite unusual for a scientific meeting to have this level of excitement!

Consider sharing this article with your healthcare provider if you’re interested in having a conversation about which diabetes medications can help beyond lowering blood sugars.