What are the indications, mechanism of action, and side effects of Dapagliflozin (Forxiga) for elderly patients with Type 2 Diabetes Mellitus (DM), hypertension, dyslipidemia, hyperuricemia, and Chronic Kidney Disease (CKD) stage 3B with impaired renal function?

Dapagliflozin for Elderly Patients with Type 2 Diabetes, Hypertension, Dyslipidemia, Hyperuricemia, and CKD Stage 3B

Dapagliflozin is indicated for this elderly patient with multiple comorbidities including CKD stage 3B (eGFR 32), as it provides cardiovascular and renal protection while managing glycemic control, though dose adjustment is required due to the reduced renal function.

Indications for Dapagliflozin in This Patient

Dapagliflozin is indicated for:

• Type 2 diabetes mellitus: As an adjunct to diet and exercise to improve glycemic control 1
• Cardiovascular risk reduction: To reduce risk of hospitalization for heart failure in patients with T2DM and established cardiovascular disease or multiple CV risk factors 2, 1
• Renal protection: To reduce progression of diabetic kidney disease and risk of sustained eGFR decline 2, 1

This patient's multiple comorbidities (T2DM, hypertension, dyslipidemia, hyperuricemia, and CKD stage 3B) make them an appropriate candidate for dapagliflozin, particularly for its cardiorenal protective effects.

Mechanism of Action

Dapagliflozin works through:

• Selective inhibition of SGLT2 receptors in the proximal convoluted tubule of the kidneys 2
• Blocking renal glucose reabsorption, leading to increased urinary glucose excretion and reduced hyperglycemia 2
• Insulin-independent mechanism of action, making it suitable for patients with long-standing diabetes 2
• Osmotic diuresis and natriuresis effects that contribute to blood pressure reduction 3
• Reduced renal cortical hypoxia by decreasing the metabolic burden on proximal tubular cells 2

Dosing Considerations for CKD Stage 3B

For this patient with eGFR of 32 ml/min/1.73m²:

• Recommended dose: 10 mg once daily 2
• Initiation is appropriate despite reduced renal function, as dapagliflozin is approved for use at 10 mg daily with eGFR 25-45 ml/min/1.73m² 2
• Glucose-lowering efficacy will be reduced at this level of renal function, but cardiovascular and renal benefits are preserved 2, 3
• Monitor renal function before initiation and periodically thereafter 1

Benefits for This Patient's Specific Conditions

1. Type 2 Diabetes:

   • Modest HbA1c reduction (approximately 0.3% at this level of renal function) 3
   • Low risk of hypoglycemia due to insulin-independent mechanism 4

2. Hypertension:

   • Blood pressure reduction through osmotic diuresis and natriuresis 3
   • BP-lowering effects remain consistent regardless of baseline eGFR 3

3. CKD Stage 3B:

   • Slows progression of diabetic kidney disease 2
   • Reduces risk of sustained eGFR decline and end-stage kidney disease 5
   • Reduces albuminuria, with greater reductions observed in patients with lower eGFR 3

4. Cardiovascular Risk:

   • Reduces risk of hospitalization for heart failure 2
   • Cardiovascular benefits observed regardless of baseline kidney function 6
   • Benefits are incremental to standard heart failure therapies 2

5. Weight Management:

   • Modest weight reduction that remains consistent regardless of baseline eGFR 3

Side Effects and Safety Considerations

Common side effects:

• Genital mycotic infections: More frequent in dapagliflozin-treated patients 4
• Urinary tract infections: May be more common than with placebo 4
• Volume depletion: Assess volume status before initiation 1
• Initial eGFR dip: An acute reduction in eGFR (>10%) is common within the first 2 weeks but does not predict worse outcomes 7

Special considerations for this elderly patient:

• Monitor for dehydration and hypotension, especially given age and reduced renal function
• Avoid in bladder cancer: Not a concern unless patient has history of bladder cancer 4
• Minimal risk of hypoglycemia when used as monotherapy, but may increase risk when combined with insulin or insulin secretagogues
• No dose adjustment needed based on age, though elderly patients may be more susceptible to volume-related adverse effects 1

Monitoring Recommendations

• Renal function: Assess eGFR before initiation and periodically thereafter
• Volume status: Monitor for signs of dehydration, especially during initial weeks of therapy
• Urinary and genital symptoms: Educate patient about increased risk of infections
• Blood pressure: Monitor for hypotension, especially if patient is on other antihypertensive medications
• HbA1c: Expect modest improvements in glycemic control

Contraindications

Dapagliflozin is contraindicated in:

• Patients on dialysis 1
• Patients with eGFR <25 ml/min/1.73m² (for initiation) 2
• Patients with active bladder cancer 4

Conclusion

For this elderly patient with T2DM, hypertension, dyslipidemia, hyperuricemia, and CKD stage 3B (eGFR 32), dapagliflozin 10 mg daily is an appropriate treatment option that offers cardiorenal protection beyond glycemic control. The benefits of reduced heart failure hospitalizations and slowed kidney disease progression make it particularly valuable despite the modest glucose-lowering effect at this level of renal function.