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Glucose-dependent insulinotropic polypeptide: difference between revisions

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Revision 45 — 19:44, 18 Jun 2025
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Revision 46 — 05:23, 4 Jul 2025
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41In obesity without diabetes, fasting GIP is elevated and the postprandial response is exaggerated, particularly to fat ingestion. Whether this hyperresponse contributes to weight gain or is a consequence of it remains unresolved. The observation that dual GIP/GLP-1 agonists produce greater weight loss than GLP-1 monotherapy is sometimes attributed to active GIP-receptor antagonism at the adipocyte, though the evidence remains limited.{{r|frias2021}}41In obesity without diabetes, fasting GIP is elevated and the postprandial response is exaggerated, particularly to fat ingestion. Whether this hyperresponse contributes to weight gain or is a consequence of it remains unresolved. The observation that dual GIP/GLP-1 agonists produce greater weight loss than GLP-1 monotherapy is sometimes attributed to active GIP-receptor antagonism at the adipocyte, though the evidence remains limited.{{r|frias2021}}
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+43== Therapeutic exploitation ==
+44GIP remained therapeutically unexploited for decades because insulinotropic beta-cell responses were thought to be lost in diabetes; the development of [[GLP-1 receptor agonist|GLP-1-directed monotherapy]] proceeded from that understanding. Dual GIP/GLP-1 receptor agonists ([[tirzepatide]], [[retatrutide]]) have demonstrated superior glycaemic control and weight loss compared to GLP-1 monotherapy in phase 3 trials, and are now approved or in development for both type 2 diabetes and obesity.{{r|frias2021,frias2022}}
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43== References ==46== References ==
44{{reflist}}47{{reflist}}
46<ref name="deacon1995">Deacon CF, Johnsen AH, Holst JJ. "Degradation of glucose-dependent insulinotropic polypeptide by human plasma in vitro yields an N-terminally truncated peptide that is a major endogenous metabolite in vivo." ''Journal of Clinical Endocrinology and Metabolism'' 80(3):952–957 (1995). PMID 7883856.</ref>49<ref name="deacon1995">Deacon CF, Johnsen AH, Holst JJ. "Degradation of glucose-dependent insulinotropic polypeptide by human plasma in vitro yields an N-terminally truncated peptide that is a major endogenous metabolite in vivo." ''Journal of Clinical Endocrinology and Metabolism'' 80(3):952–957 (1995). PMID 7883856.</ref>
47<ref name="frias2021">Frías JP, Davies MJ, Rosenstock J, et al. "Tirzepatide versus semaglutide oral in type 2 diabetes." ''New England Journal of Medicine'' 385(6):503–515 (2021). DOI:10.1056/NEJMoa2107519. PMID 34170647.</ref>50<ref name="frias2021">Frías JP, Davies MJ, Rosenstock J, et al. "Tirzepatide versus semaglutide oral in type 2 diabetes." ''New England Journal of Medicine'' 385(6):503–515 (2021). DOI:10.1056/NEJMoa2107519. PMID 34170647.</ref>
+51<ref name="frias2022">Frías JP, Nauck MA, Van J, et al. "Efficacy and tolerability of tirzepatide for type 2 diabetes: a phase 3, randomised, controlled trial." ''The Lancet'' 398(10308):1228–1239 (2021). DOI:10.1016/S0140-6736(21)01324-6. PMID 34706170.</ref>
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49== Further reading ==53== Further reading ==
50* Seino S, Fukushima M, Yabe D. "GIP and GLP-1, the two incretin hormones: Similarities and differences." ''Journal of Diabetes Investigation'' 1(3):8–23 (2010).54* Seino S, Fukushima M, Yabe D. "GIP and GLP-1, the two incretin hormones: Similarities and differences." ''Journal of Diabetes Investigation'' 1(3):8–23 (2010).
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+56== External links ==
+57* [https://www.ncbi.nlm.nih.gov/gene/2695 GIP — Gene entry] — NCBI Gene record for the GIP gene.
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52== See also ==59== See also ==