PMID-29364588 – Incretin Hormones Their Role in Health and Disease
Nauck MA, Meier JJ. Incretin Hormones: Their Role in Health and Disease. Diabetes Obes Metab. 2018;20(Suppl 1):5-21.
Quick Reference
| Property | Value |
|---|---|
| PMID | 29364588 |
| DOI | 10.1111/dom.13129 |
| Year | 2018 |
| Journal | Diabetes, Obesity and Metabolism |
| Study Type | Narrative Review |
| Evidence Level | V |
| Sample | N/A (authoritative review by incretin effect co-discoverer) |
| Peptide(s) Studied | GLP-1 (Native) |
Key Findings
- The incretin effect (oral glucose eliciting greater insulin response than IV glucose at matched glycemia) accounts for 50-70% of postprandial insulin secretion in healthy individuals
- GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 are the two primary incretin hormones, with complementary but distinct receptor distributions and signaling profiles
- In type 2 diabetes, the incretin effect is markedly impaired: GIP loses most of its insulinotropic potency while GLP-1 retains partial efficacy, explaining why GLP-1 became the preferred therapeutic target
- The DPP-4 enzyme degrades both GIP and GLP-1 within minutes of secretion, establishing the pharmacological rationale for both DPP-4 inhibitors and DPP-4-resistant GLP-1 receptor agonists
- GLP-1 exerts pleiotropic effects beyond glycemic control: cardiovascular protection, neuroprotection, anti-inflammatory activity, and hepatic steatosis reduction
- The review traces the full translational arc from Nauck's original incretin effect observations (1986) through to the approved therapeutic classes (GLP-1RAs, DPP-4i, and dual GIP/GLP-1 agonists)
Study Design
Authoritative narrative review by Michael Nauck, who co-discovered the impaired incretin effect in type 2 diabetes. Integrates foundational physiology, receptor pharmacology, clinical trial evidence, and therapeutic development history across three decades.
Limitations
- Published in 2018, does not cover the STEP (semaglutide obesity) or SURMOUNT (tirzepatide obesity) trial programs that transformed the field
- The dual agonist (GIP/GLP-1) section is speculative, predating tirzepatide's approval and clinical outcomes data
- Does not address the triple agonist (GIP/GLP-1/glucagon) class such as retatrutide
Clinical Relevance
Essential reading for understanding why GLP-1-based therapies dominate the current diabetes and obesity treatment landscape. Provides the physiological foundation needed for Module 5 (Weight Loss & Body Composition) and explains why the incretin axis is a legitimate therapeutic target. The impaired incretin effect in T2D patients directly justifies exogenous GLP-1 receptor activation as a treatment strategy.
Related
#research #narrative-review #glp-1 #evidence-level-V