What is the therapeutic dose of saxagliptin in adults with type 2 diabetes, and the dose adjustments for moderate renal impairment (eGFR 30–50 mL/min/1.73 m²) and hepatic impairment?

Therapeutic Dosing of Saxagliptin in Type 2 Diabetes

The standard therapeutic dose of saxagliptin is 5 mg once daily, but this must be reduced to 2.5 mg once daily in patients with moderate or severe renal impairment (eGFR 30–50 mL/min/1.73 m² or eGFR <30 mL/min/1.73 m²), including those with end-stage renal disease on hemodialysis. 1, 2, 3, 4

Standard Dosing in Normal Renal Function

• For adults with type 2 diabetes and normal renal function (eGFR ≥50 mL/min/1.73 m²), saxagliptin 5 mg once daily is the recommended dose. 2, 3
• Saxagliptin can be administered with or without food, as meals do not affect its pharmacokinetics. 1
• The half-life of DPP-4 inhibition is approximately 27 hours, supporting once-daily dosing. 1

Renal Dose Adjustments

Moderate Renal Impairment (eGFR 30–50 mL/min/1.73 m²)

• Reduce the dose to 2.5 mg once daily when eGFR is 30–50 mL/min/1.73 m². 2, 3, 4
• This reduction is necessary because saxagliptin exposure (AUC) increases by 41% and the active metabolite 5-hydroxy saxagliptin increases by 192% (2.9-fold) in moderate renal impairment. 4

Severe Renal Impairment (eGFR <30 mL/min/1.73 m²)

• Reduce the dose to 2.5 mg once daily when eGFR is <30 mL/min/1.73 m² (not on dialysis). 2, 3, 4
• Saxagliptin exposure increases by 108% (2.1-fold) and 5-hydroxy saxagliptin increases by 347% (4.5-fold) in severe renal impairment. 4

End-Stage Renal Disease (ESRD) on Hemodialysis

• Use 2.5 mg once daily in patients with ESRD requiring hemodialysis. 2, 3, 4
• Only 23% of the saxagliptin dose is cleared during a 4-hour hemodialysis session, so timing relative to dialysis is not critical. 4
• Long-term data (52 weeks) demonstrate sustained efficacy and good tolerability at the 2.5 mg dose in patients with ESRD. 5

Hepatic Impairment

• No dose adjustment is required for any degree of hepatic impairment (mild, moderate, or severe). 1, 4
• Saxagliptin exposure increases by only 10–77% across all degrees of hepatic impairment, which is not clinically meaningful. 4

Drug Interaction Considerations

• When saxagliptin is coadministered with strong CYP3A4/5 inhibitors (e.g., ketoconazole, clarithromycin, ritonavir), limit the dose to 2.5 mg once daily. 1, 2, 3
• This reduction is necessary because strong CYP3A4 inhibitors increase saxagliptin exposure, similar to the effect seen in renal impairment. 1

Clinical Context and Positioning

• DPP-4 inhibitors like saxagliptin should be considered only when SGLT2 inhibitors and GLP-1 receptor agonists are contraindicated, not tolerated, or unavailable, as the latter agents provide superior cardiovascular and renal protection. 6
• Saxagliptin reduces HbA1c by approximately 0.5% as monotherapy and demonstrates greater efficacy when combined with metformin, sulfonylureas, or thiazolidinediones. 2, 3
• The drug is generally well tolerated, with the most common adverse events being upper respiratory tract infection, headache, and urinary tract infection. 2, 3

Safety in Renal Impairment

• Saxagliptin 2.5 mg once daily offers sustained efficacy over 52 weeks in patients with moderate or severe renal impairment and ESRD, with a similar incidence of hypoglycemia compared to placebo (28% vs. 29%). 5
• The low hypoglycemia risk is due to saxagliptin's glucose-dependent mechanism of action, which preserves pancreatic beta-cell function without forcing insulin secretion when glucose levels are normal. 3

Common Pitfalls to Avoid

• Do not use the standard 5 mg dose in patients with eGFR <50 mL/min/1.73 m², as this leads to excessive drug accumulation and increased exposure to both saxagliptin and its active metabolite. 4
• Do not prioritize saxagliptin over SGLT2 inhibitors or GLP-1 receptor agonists in patients with established cardiovascular disease, heart failure, or chronic kidney disease, as saxagliptin lacks the mortality and morbidity benefits demonstrated by these agents. 6
• Measure eGFR before initiating saxagliptin and monitor every 3–6 months when eGFR <60 mL/min/1.73 m² to ensure appropriate dose adjustment if renal function declines. 6