DAPA-CKD: Renal benefits of SGLT2 inhibition in people with and without diabetes | Hiddo Heerspink

Summary

This study investigated the effects of dapagliflozin on patients with chronic kidney disease, revealing a significant reduction in kidney failure, cardiovascular death, and heart failure hospitalization. The trial included a diverse population, with findings indicating dapagliflozin was equally effective in patients with and without type 2 diabetes. Importantly, the study demonstrated the drug's safety profile, with minimal adverse events. Mechanistically, dapagliflozin reduces glomerular pressure, offering renal protection. These results extend to early-stage chronic kidney disease, suggesting potential preventive benefits when administered before significant decline occurs.

Takeaways

• 😀 The study included adult patients with chronic kidney disease (CKD) and specified eGFR and urinary albumin levels.
• 😀 Approximately 66% of the study population had type 2 diabetes, which is consistent with clinical practice where diabetes is common in CKD patients.
• 😀 Dapagliflozin significantly reduced the risk of kidney failure and cardiovascular death after 2.2 years of follow-up.
• 😀 The trial was stopped early due to overwhelming efficacy observed in patients taking dapagliflozin compared to placebo.
• 😀 Primary and secondary outcomes showed statistically significant reductions, including a 39% risk reduction for the primary endpoint.
• 😀 The drug was found to be effective in both patients with and without type 2 diabetes, indicating its broad applicability.
• 😀 Dapagliflozin demonstrated consistent results across pre-specified subgroups based on various demographic and clinical factors.
• 😀 The drug was well-tolerated, with no significant adverse events like diabetic ketoacidosis reported in the treatment group.
• 😀 Concerns about SGLT2 inhibitors harming kidneys have been alleviated by evidence showing renal protection and reduced kidney function decline.
• 😀 Early administration of SGLT2 inhibitors could prevent the progression of kidney disease in patients with early-stage diabetes.

Q & A

What was the study population for the trial?

The study included adult patients with chronic kidney disease, specifically those with an eGFR between 25 and 75 ml/min and urinary albumin excretion between 200 and 5,000 mg/g creatinine.

Did the study include patients with type 2 diabetes?

Yes, patients with type 2 diabetes were included, but the study also specified that at least 30% of participants should not have diabetes, which was achieved.

What were the primary findings of the study regarding dapagliflozin?

The study found that dapagliflozin significantly reduced the risk of kidney failure, cardiovascular death, and heart failure hospitalization, with statistically significant reductions across all primary and secondary outcomes.

How did dapagliflozin affect patients with and without type 2 diabetes?

In patients with type 2 diabetes, there was a 36% relative risk reduction for the primary outcome, while in those without diabetes, the reduction was 50%. The p-value for interaction indicated no significant difference in efficacy between the two groups.

What were the results regarding safety and adverse events associated with dapagliflozin?

Dapagliflozin was well-tolerated, with similar rates of adverse events and discontinuations due to adverse events compared to placebo. Importantly, there were no cases of diabetic ketoacidosis in the dapagliflozin group.

Why was there initial concern about the effects of SGLT2 inhibitors on kidney health?

Concerns arose from the idea that increased glucose in the proximal tubule due to SGLT2 inhibition could lead to kidney damage. However, recent trials have demonstrated that these inhibitors are actually renal protective.

What mechanisms contribute to the kidney protective effects of SGLT2 inhibitors?

One mechanism involves the reduction of pressure in the glomeruli through tubuloglomerular feedback, which leads to decreased renal blood flow and, over time, preservation of kidney function.

Can SGLT2 inhibitors prevent the decline of kidney function in early-stage diabetes?

Yes, trials like the DECLARE study have shown that SGLT2 inhibitors can significantly slow the progression of kidney function decline in patients with early stages of chronic kidney disease.

What percentage of patients with type 2 diabetes develop diabetic kidney disease?

Approximately 40% of all patients with type 2 diabetes will develop diabetic kidney disease.

What was the duration of follow-up in the study, and what triggered its early termination?

The study had a follow-up duration of about 2.2 to 2.4 years, and it was stopped early due to overwhelming efficacy as recommended by the data monitoring board.