While the class of medications called SGLT2 inhibitors were originally developed as treatments for type 2 diabetes, we are learning that people without diabetes can benefit from these medications as well. At the European Society of Cardiology meeting this weekend, two landmark trials were released which add to our knowledge in this area: the DAPA-CKD study, and the EMPEROR-reduced trial.
The DAPA-CKD study (presented today) was the first of its kind, evaluating whether the SGLT2 inhibitor dapagliflozin (Forxiga) can protect kidneys in people with chronic kidney disease, with or without type 2 diabetes. They enrolled 4,304 patients who had chronic kidney disease, 68% of whom had type 2 diabetes and 32% of whom did not. The primary endpoint was a combination of ≥50% sustained decline in eGFR, reaching end stage kidney disease, cardiovascular or renal death. The study found that dapagliflozin reduced the risk of reaching the primary endpoint by 39% over a mean of 2.4 years; said another way, only 19 people needed to be treated to prevent one event. This benefit was enjoyed both by people with diabetes (36% risk reduction) and without diabetes (50% risk reduction).
The DAPA-CKD study adds to the knowledge from the CREDENCE trial of canagliflozin published in 2019. The CREDENCE trial showed that the SGLT2 inhibitor canagliflozin was very powerful to protect kidneys in people with chronic kidney disease and type 2 diabetes. The DAPA-CKD study adds to this data, showing similar benefit in people not only in people with type 2 diabetes, but also in people without diabetes. (note: the DAPA-CKD study has not been published yet; also, stay tuned to drsue.ca for more on this trial and how it impacts patient care in coming weeks as the medical community processes this important information!)
The EMPEROR-reduced trial, published in the New England Journal of Medicine simultaneously with presentation on august 29th, evaluated the safety and efficacy of SGLT2 inhibitor empagliflozin (Jardiance) as a heart failure treatment in people with heart failure with reduced ejection fraction (HFrEF). Amongst 3,730 patients enrolled in the study, half had type 2 diabetes and half did not. After a median of 16 months, the study found that empagliflozin reduced the primary endpoint of hospitalization for heart failure + cardiovascular death by 25%, and this benefit was the same for people with or without diabetes. This finding was driving by a 30% reduction in hospitalization for heart failure; the reduction in cardiovascular death was not significant.
The main finding of the EMPEROR-reduced trial is similar to the findings of the DAPA-HF trial published in 2019. Both studies showed that these medication are very effective to treat heart failure, both in people with AND without type 2 diabetes. Interestingly, however, the DAPA-HF trial showed a reduction in cardiovascular death, whereas the EMPEROR-reduced trial did not. Conversely, in the original diabetes cardiovascular outcome trial of empagliflozin, called EMPA-REG, there was a reduction in cardiovascular death, whereas in dapagliflozin’s DECLARE trial, there was not. As noted in the NEJM editorial accompanying the EMPEROR-reduced trial, while the SGLT2 inhibitors seem be quite consistent in their ability to reduce and treat heart failure as well as protect kidneys, they do not seem to be entirely consistent with regard to their ability to reduce cardiovascular events.
BOTTOM LINES: We now have evidence to show that the SGLT2 inhibitor dapagliflozin can protect kidneys not only in people with diabetes, but also those without diabetes. We now also have expanding data supporting the benefit of SGLT2 inhibitors as a treatment for heart failure, in people with or without type 2 diabetes. The SGLT2 inhibitors should no longer be viewed just as diabetes treatments, but rather as important treatments for people with chronic kidney disease and heart failure.
Disclaimer: I receive honoraria as a continuing medical education speaker and consultant from the makers of SGLT2 inhibitors dapagliflozin (Astra Zeneca), empagliflozin (Boehringer Ingelheim/Eli Lilly), and canagliflozin (Janssen). I have been involved as an investigator in clinical trials of SGLT2 inhibitors.
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