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©The Author(s) 2022.
World J Diabetes. Feb 15, 2022; 13(2): 85-96
Published online Feb 15, 2022. doi: 10.4239/wjd.v13.i2.85
Published online Feb 15, 2022. doi: 10.4239/wjd.v13.i2.85
Table 1 Characteristics of dipeptidyl peptidase 4 inhibitors
Chemistry | Half-life | HbA1c reduction (%) | Metabolism | Eliminationroute | |
Alogliptin | Modifiedpyrimidinedione | 20 h | 0.6 (mean value) | Minimal | Predominantly (> 70%) renal |
Linagliptin | Xanthine-based | Approxmately 12 h (effective), > 100 h (terminal) | 0.5-0.7 | Minimal | Predominantly biliary (< 6% renal) |
Saxagliptin | Cyanopyrrolidine | 2.5 h (parent), 3 h (metabolite) | 0.5-1.0 | Hydrolysis (cytochrome P450 3A4 or P450 3A5) to form an active metabolite | Metabolism (parent) and renal (metabolite) |
Sitagliptin | β-aminoacid based | 12.5 h | 0.5-1.0 | Minimal | Predominantly (> 80%) |
Vildagliptin | Cyanopyrrolidine | Approxmately 2 h | 0.9 (mean value) | Hydrolysis (cytochrome-independent) to form an inactive metabolite | Metabolism (parent) and renal (metabolite) |
Table 2 Renal dosing of dipeptidyl peptidase 4 inhibitors
Renal impairment | Alogliptin | Linagliptin | Sitagliptin | Vildagliptin | Saxagliptin |
Mild (eGFR > 50 mL/min) | 25 mg o.d. | 5 mg o.d. | 100 mg o.d. | 50 mg b.i.d. | 5 mg o.d. |
Moderate (eGFR 30-50 mL/min) | 12.5 mg o.d. | 5mg o.d. | 50 mg o.d. | 50 mg o.d. | 2.5 mg o.d. |
Severe (eGFR < 30 mL/min) | 6.25 mg o.d. | 5 mg o.d. | 25 mg o.d. | 50 mg o.d. | 2.5 mg o.d. |
ESRD | 6.25 mg o.d. | 5 mg o.d. | 25 mg o.d. | 50 mg o.d. | Contraindicated |
Renal dialysis | 6.25 mg o.d. | 5 mg o.d. | 25 mg o.d. | 50 mg o.d. | Contraindicated |
Table 3 Modification of dosing for dipeptidyl peptidase 4 inhibitors in hepatic impairment
Hepatic impairment | Alogliptin | Linagliptin | Sitagliptin | Vildagliptin | Saxagliptin |
Mild | 25 mg o.d. | 5 mg o.d. | 100 mg o.d. | Not recommended in liver disease, including AST or ALT > 3 × ULN | 5 mg o.d. |
Moderate | 25 mg o.d. | 5mg o.d. | 100 mg o.d. | Can be used with caution | |
Severe | Not recommended | 5 mg o.d. | Can be used with caution | Not recommended |
Table 4 Cardiovascular outcome trials with dipeptidyl peptidase 4 inhibitors
CVOT | Comparator | Cardiovascular safety (MACE) (HR) | Risk of hospitalization for heart failure (HR) | |
Alogliptin | EXAMINE | Placebo | 0.96 | 1.07 |
Linagliptin | CARMELINA | Placebo | 1.02 | 0.90 |
CAROLINA | Glimepiride | 0.98 | 1.21 | |
Saxagliptin | SAVOR-TIMI | Placebo | 1.00 | 1.27 |
Sitagliptin | TECOS | Placebo | 0.98 | 1.00 |
- Citation: Florentin M, Kostapanos MS, Papazafiropoulou AK. Role of dipeptidyl peptidase 4 inhibitors in the new era of antidiabetic treatment. World J Diabetes 2022; 13(2): 85-96
- URL: https://www.wjgnet.com/1948-9358/full/v13/i2/85.htm
- DOI: https://dx.doi.org/10.4239/wjd.v13.i2.85