Dipeptidyl peptidase-4: difference between revisions
Diff·revision 13 → 14·13:03, 13 Jan 2025
Difference between revision 13 and revision 14 of Dipeptidyl peptidase-4. 5 lines changed; the page grew by 856 bytes.
| Revision 13 — 04:50, 26 Dec 2024 ColdChainCleo (talk) expand §Catalytic action and substrate range 4,907 bytes +571 | Revision 14 — 13:03, 13 Jan 2025 HalfLifeHavel (talk) the numbers in the lead disagreed with the body; body was right 5,763 bytes +856 | ||
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| 41 | Substitution alone is not sufficient for a long dosing interval — a DPP-4-resistant peptide is still cleared renally within hours — so the resistant residue is almost always combined with an [[Albumin binding half-life extension|albumin-binding]] or fusion strategy. Semaglutide combines both, and adds a substitution at position 34 to prevent acylation at the wrong lysine.{{r|knudsen2019}} | 41 | Substitution alone is not sufficient for a long dosing interval — a DPP-4-resistant peptide is still cleared renally within hours — so the resistant residue is almost always combined with an [[Albumin binding half-life extension|albumin-binding]] or fusion strategy. Semaglutide combines both, and adds a substitution at position 34 to prevent acylation at the wrong lysine.{{r|knudsen2019}} |
| 42 | 42 | ||
| + | 43 | == DPP-4 inhibitors as a drug class == | |
| + | 44 | Sitagliptin, vildagliptin, saxagliptin, linagliptin and alogliptin inhibit the enzyme competitively or, in some cases, through a covalent but reversible interaction with the catalytic serine. They raise intact GLP-1 and GIP concentrations into the low postprandial physiological range rather than the supraphysiological range achieved by injected agonists.{{r|deacon2019}} | |
| + | 45 | ||
| + | 46 | The clinical consequences follow from that ceiling. Glycated-haemoglobin reduction is modest, weight is unchanged rather than reduced, and gastrointestinal adverse effects are uncommon — the same mechanism that limits efficacy also limits toxicity. Cardiovascular outcome trials of the class have been neutral for major adverse cardiovascular events, with a signal for heart-failure hospitalisation reported for one member.{{r|deacon2019}} | |
| + | 47 | ||
| 43 | == References == | 48 | == References == |
| 44 | {{reflist}} | 49 | {{reflist}} |