Summary: Dapagliflozin has shown significant potential in treating chronic kidney disease (CKD) beyond its role in managing type 2 diabetes. The DAPA-CKD trial revealed a 39% reduction in adverse kidney outcomes and a 31% decrease in all-cause mortality among patients. These findings highlight dapagliflozin’s renoprotective effects, making it a promising therapy for CKD management.
Dapagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, is widely recognized for managing type 2 diabetes by reducing glucose reabsorption in the kidneys. It is now understood that SGLT2 inhibitors possess therapeutic potential that extends beyond glucose management, showing promise in treating various forms of chronic kidney disease (CKD). Preventing CKD by Dapagliflozin or other SGLT2 inhibitors should not be surprising at all since chronically elevated glucose levels cause severe long term kidney damage, in fact the number one cause of renal transplants is the long term complications of diabetes.
Understanding Chronic Kidney Disease
Chronic kidney disease encompasses a range of conditions that cause a gradual loss of kidney function over time; however, in the context of diabetes, glycation of various proteins in the kidney from uncontrolled diabetes is the most common cause of the need for renal transplant. Initially, the CKD starts by the patient having an eGRF of less than 60 ml/min/1.73m2 for 3 months or more, but when the GFR becomes less than 15 ml/min/1.73m2, they require a renal transplant.
Dapagliflozin’s Role in CKD
The DAPA-CKD (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease) trial highlighted significant benefits of dapagliflozin in patients with CKD:
- Primary Endpoint Reduction: There was a 39% reduction in the composite endpoint of sustained decrease in estimated glomerular filtration rate (eGFR) ≥ 50%, onset of ESRD, or death from renal or cardiovascular causes in the dapagliflozin group compared to placebo.
- Decreased Mortality: All-cause mortality was 31% lower among patients receiving a 10 mg dose of dapagliflozin versus the placebo group.
- Long-Term Benefits: Over a 10-year projection, patients on dapagliflozin spent 0.65 years more in CKD stages 1–3 and 0.23 years less in stages 4–5. The treatment could prevent an estimated 83 deaths and delay the need for kidney replacement therapy in 51 patients per 1,000 treated.
- Reduced Cardiovascular Events: Predicted rates of hospitalized heart failure and abrupt declines in kidney function were reduced by 19 and 39 events per 1,000 patients, respectively.
Consistency Across Patient Profiles
The benefits of dapagliflozin were consistent regardless of the baseline use of cardiovascular medications such as:
- Renin-angiotensin-aldosterone system inhibitors
- Calcium channel blockers
- Beta-adrenergic antagonists
- Diuretics
Conclusion
In some sense, it is not surprising to find that any medication that successfully lowers blood sugar will have protective effects on the kidneys. However, the magnitude with which Dapagliflozin can be renoprotective with relatively few adverse events is astonishing. It is important to note that Dapagliflozin medicine may be a poor choice for individuals that had a significant UTI history or pyelonephritis as these individuals are much more likely to get the adverse events than someone without a UTI history. If one understands that SGLT2i increases the amount of sugar that is in the urine and that bacteria like to use sugar to multiply, then it should make sense to avoid giving a medicine like Dapagliflozin to someone with prior UTI that was severe or numerous.
Note: Always consult a healthcare professional before starting any new medication or treatment plan.
