Maximum Doses of Dapagliflozin and Linagliptin in Stage 3b CKD
For a patient with stage 3b CKD (eGFR 30-44 mL/min/1.73 m²) and diabetes, the maximum dose of dapagliflozin is 10 mg once daily and linagliptin is 5 mg once daily, with no dose adjustment required for either medication at this level of renal function. 1
Dapagliflozin Dosing in Stage 3b CKD
The standard dose of dapagliflozin remains 10 mg once daily in stage 3b CKD, regardless of whether the indication is glycemic control, cardiovascular protection, or renal protection. 1, 2
Key Dosing Principles
- At eGFR 30-44 mL/min/1.73 m², dapagliflozin 10 mg daily is the recommended dose and no reduction is required 1
- While dapagliflozin is not recommended for initiation when eGFR <25 mL/min/1.73 m², it can be continued at 10 mg daily if already established on therapy 1, 2
- The glucose-lowering efficacy decreases significantly when eGFR <45 mL/min/1.73 m², but cardiovascular and renal protective benefits are preserved at lower eGFR levels 2
Evidence Supporting This Dosing
- The DAPA-CKD trial, which demonstrated a 39% reduction in the composite outcome of sustained eGFR decline, end-stage kidney disease, or renal/cardiovascular death, used a fixed dose of 10 mg daily in patients with eGFR 25-75 mL/min/1.73 m² 3, 4
- The trial protocols specified continuation of dapagliflozin 10 mg daily even when eGFR fell below initiation thresholds during the study 1
Linagliptin Dosing in Stage 3b CKD
Linagliptin requires no dose adjustment regardless of renal function, with the standard dose remaining 5 mg once daily even in severe renal impairment. 1, 5
Unique Renal Advantage
- Linagliptin is the only DPP-4 inhibitor that does not require dose adjustment at any level of renal impairment, including stage 3b CKD 1, 5
- In contrast, other DPP-4 inhibitors require dose reductions: sitagliptin must be reduced to 50 mg daily at eGFR 30-44 mL/min/1.73 m², saxagliptin to 2.5 mg daily, and alogliptin to 12.5 mg daily 1
- Steady-state exposure of linagliptin increases only 40-42% in severe renal impairment, which is not clinically significant and does not necessitate dose adjustment 2, 5
Clinical Algorithm for Combined Use
When using both medications together in stage 3b CKD:
- Dapagliflozin: Start or continue 10 mg once daily 1, 2
- Linagliptin: Start or continue 5 mg once daily 1, 5
- Monitor eGFR within 1-2 weeks after initiating dapagliflozin, as an acute reversible decline of 3-5 mL/min/1.73 m² is expected 2
- Continue both medications at these doses even if eGFR declines further, unless dialysis is initiated 1, 2
Important Safety Considerations
For Dapagliflozin
- Assess volume status before initiation and consider reducing concurrent diuretic doses to prevent excessive volume depletion 1, 2
- Withhold dapagliflozin during acute illness, particularly with reduced oral intake, fever, vomiting, or diarrhea 2
- Maintain at least low-dose insulin in insulin-requiring patients even when dapagliflozin is held during illness 1
- Monitor for genital mycotic infections, which occur in approximately 6% of patients on SGLT2 inhibitors 1, 2
For Linagliptin
- Minimal hypoglycemia risk when used as monotherapy, but increases approximately 50% when combined with sulfonylureas 5
- Avoid saxagliptin and alogliptin in patients with heart failure risk, but linagliptin has neutral cardiovascular safety 5
Common Pitfall to Avoid
Do not discontinue dapagliflozin solely because eGFR falls below 45 mL/min/1.73 m² or even below 30 mL/min/1.73 m² in stage 3b CKD, as the cardiovascular and renal protective benefits persist even when glycemic efficacy is lost. 1, 2 The initial eGFR dip of 3-5 mL/min/1.73 m² within the first 1-4 weeks is transient, reversible, and does not require drug discontinuation 1, 2