Table 1.
Commercial dipeptidyl peptidase-IV inhibitors.
| Attributes of marketed drugs | Sitagliptins | Vildagliptins | Saxagliptins | Alogliptins | Linagliptin |
|---|---|---|---|---|---|
| DPP-IV inhibition (%) | More than 80%–90% | More than 90% | 75%–80% | More than 80% | More than 80% |
| Specificity for DPP-IV and type of inhibition | Very high, competitive, and dose-dependent inhibitor | High affinity (but not as sitagliptin) as compared with sitagliptin; it acts as a substrate blocker | Moderate affinity, selective, reversible, competitive inhibitor | High affinity, competitive, and dose-dependent inhibitor | High affinity, high specificity, and dose dependent inhibitor |
| HbA1C reduction (%) | 0.6% only sitagliptin 0.89% with metformin |
0.7% | 0.45–0.65% | 0.6% with sitagliptin 0.7% with vildagliptin |
0.53% |
| Hypoglycemia risk | No risk detected | No risk detected | No risk detected | No risk detected | No risk detected |
| Mean half life | 8–14 h | 1.3–2.4 h | 2.5 h | 12.4–21.4 h | 12 h |
| Bioavailability | ±87% | ±85% | ±67% | 100% | ±30% |
| Metabolism/elimination | Primary route: kidneys (only 16%) About 74% has been accounted for as parental drug |
Primary route: kidneys About 85.04% fraction of the drug is absorbed and recovered in urine, wherein 27.14% (22.60 % recovered in urine and 4.54% recovered in feces) is unchanged parental drug and 57.90% is after hydrolysis |
Primary route: kidneys and liver Liver: metabolizes the drug by cytochrome P450 enzymes and forming an active metabolite Kidney: as renal circulation 22.1% as an unchanged parent compound and 44.1% as a metabolite |
About 60% to 80% of the administered dose tends to be unchanged in the urine after 24 to 72 h and 10%–20% of the dose is hepatically metabolized by cytochrome enzymes Primary excretion: kidneys (76%) Secondary: fecal (13%) Two minor metabolites explored were N-demethylated alogliptin (inhibitor of DPP-IV) and N-acetylated alogliptin |
About 70%–80% of the administered drug is bound to plasma proteins Primary excretion: bile and gut Secondary excretion: kidneys |
| Year of approval | 2006 | 2007 | 2009 | 2013 | 2011 |
| Brand name | Januvia | Galvus | Onglyza | Nesina | Tradjenta |