What is the relationship between Farxiga (dapagliflozin) and microvascular disease?

From the Guidelines

Farxiga (dapagliflozin) has been shown to reduce the risk of microvascular disease complications in patients with type 2 diabetes, particularly in those with chronic kidney disease (CKD). As an SGLT2 inhibitor, Farxiga primarily works by preventing glucose reabsorption in the kidneys, leading to increased glucose excretion in urine and improved glycemic control. For patients with type 2 diabetes at risk for microvascular complications, the typical dosage is 10 mg once daily, taken in the morning with or without food. The Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial, which is the most recent and highest quality study, demonstrated that dapagliflozin significantly reduced the risk of the primary composite outcome of ≥50% sustained decline in eGFR, end-stage kidney disease, or cardiovascular death by 39% (HR 0.61 [95% CI 0.51–0.72]; P < 0.001) 1. Some key benefits of Farxiga include:

• Reduced albuminuria and slowing the progression of diabetic kidney disease, a significant microvascular complication
• Maintenance of stable blood glucose levels, crucial for preventing diabetic retinopathy and neuropathy
• Multiple mechanisms of action, including reduced hyperfiltration in the kidneys, decreased inflammation, and improved vascular function
• Patients should maintain adequate hydration while taking Farxiga and be monitored for potential side effects such as genital mycotic infections, urinary tract infections, and volume depletion. While Farxiga is beneficial for microvascular disease prevention, it should be used as part of a comprehensive diabetes management plan that includes lifestyle modifications and potentially other medications to achieve optimal glycemic control. The most recent evidence from the DAPA-CKD trial 1 and other studies 1 supports the use of Farxiga in patients with type 2 diabetes and CKD to reduce the risk of microvascular disease complications.

From the FDA Drug Label

The Trial to Evaluate the Effect of Dapagliflozin on Renal Outcomes and Cardiovascular Mortality in Patients with Chronic Kidney Disease (DAPA-CKD, NCT03036150) was an international, multicenter, randomized, double-blind, placebo-controlled trial in adult patients with chronic kidney disease (CKD) Dapagliflozin reduced the incidence of the primary composite endpoint of ≥50% sustained decline in eGFR, progression to ESKD, CV or renal death [HR 0.61 (95% CI 0.51,0.72); p<0. 0001]. Dapagliflozin also reduced the incidence of the composite endpoint of CV death or hospitalization for heart failure [HR 0.71 (95% CI 0.55,0.92), p=0.0089] and all-cause mortality [HR 0.69 (95% CI 0.53,0.88), p=0. 0035].

The relationship between Farxiga (dapagliflozin) and microvascular disease is that dapagliflozin has been shown to reduce the incidence of microvascular complications such as kidney disease progression in patients with chronic kidney disease, as evidenced by the DAPA-CKD trial 2.

• Key findings include a reduced incidence of ≥50% sustained decline in eGFR, progression to ESKD, CV or renal death.
• Dapagliflozin also reduced the incidence of CV death or hospitalization for heart failure and all-cause mortality.

From the Research

Relationship between Farxiga (dapagliflozin) and microvascular disease

• The study 3 modeled the effects of dapagliflozin treatment on cardiovascular and microvascular outcomes, and found that dapagliflozin was projected to reduce the incidence of microvascular complications such as end-stage renal disease, foot amputation, and diabetic retinopathy by 18.7%, 13.0%, and 9.8%, respectively, over a 20-year period.
• A randomized study 4 found that 6 weeks of dapagliflozin treatment resulted in improvements in retinal capillary flow and reduced arteriole remodelling, suggesting a beneficial effect on microvascular structure and function.
• The same study 4 also found that dapagliflozin treatment resulted in improvements in diabetes control, including blood glucose and insulin resistance, and reduced office and 24-h ambulatory blood pressure values, which may also contribute to a reduction in microvascular disease.
• Another study 5 found that dapagliflozin reduced the risk of renal adverse events, which may also be related to a reduction in microvascular disease.
• Overall, the evidence suggests that dapagliflozin may have a beneficial effect on microvascular disease, although more research is needed to fully understand the relationship between dapagliflozin and microvascular disease.

Key findings

• Dapagliflozin reduces the incidence of microvascular complications such as end-stage renal disease, foot amputation, and diabetic retinopathy 3.
• Dapagliflozin improves retinal capillary flow and reduces arteriole remodelling 4.
• Dapagliflozin reduces the risk of renal adverse events 5.
• Dapagliflozin improves diabetes control, including blood glucose and insulin resistance, and reduces office and 24-h ambulatory blood pressure values 4.