Table 1.
| Parameters | Sitagliptin16 | Saxagliptin17 | Linagliptin18 | Alogliptin19 |
|---|---|---|---|---|
| Recommended (once-daily) dosea (mg) | 100 | 2.5 and 5 | 5 | 25 |
| Selectivity | ||||
| vs DPP-8/9 (fold) | >2,600 | <100 | >10,000 | >14,000 |
| vs DPP-2 (fold) | >5,550 | >50,000 | >100,000 | >14,000 |
| Clinical PK | ||||
| Bioavailability (%) | 87 | 67b | ~30 | ~100 |
| Protein-bound (%) | 38 | Negligible | ~99% at <1 nmol/L to 75%–89% at ≥30 nmol/L | 20 |
| CYP enzymes | Minor | CYP3A4/5 | Minimal | Minimal |
| t1/2, h (after oral dosing) | ~12 | Saxagliptin: 2.5, BMS 5510849 (active metabolite): 3.1 | >100 | 21 |
| Renal excretion (%) | 87 | 75 | 5 | 76 |
| Dose reduction with renal impairment | Yes, dose adjustment for moderate RI (50 mg once daily), and severe RI or ESRD (25 mg once daily) | Yes, dose adjustment for moderate or severe RI, or ESRD (2.5 mg once daily) | No (not required) | Yes, dose adjustment for moderate RI (12.5 mg once daily), or severe RI, or ESRD (6.25 mg once daily) |
Notes:
a
See also Table 3 data on renal impairment.
b
Predicted bioavailability.
Abbreviations: CYP, cytochrome P450; DPP, dipeptidyl peptidase; ESRD, end-stage renal disease; PK, pharmacokinetic; RI, renal impairment; t1/2, elimination half-life.