Incretin-based therapies: GLP-1 receptor agonists, dual agonists and DPP-4 inhibitors
The incretin effect, why GLP-1 receptor agonists and tirzepatide lower glucose without much hypoglycaemia, how half-life engineering sets weekly dosing and slow titration, the outcome trials, and the adverse effects (nausea, gallstones, retinopathy, aspiration) that follow from the mechanism. DPP-4 inhibitors for comparison.
Tier 1Medical sciences concept
Written with AI assistance and fact-checked against the sources below. For exam study, not clinical decisions. How notes are made
At a glance
- Glucagon-like peptide-1 (GLP-1) comes from ileal and colonic L cells; glucose-dependent insulinotropic polypeptide (GIP) from duodenal and jejunal K cells. Both amplify meal-stimulated insulin release.
- GLP-1 receptor agonists (GLP-1 RAs) give pharmacological receptor stimulation. DPP-4 inhibitors only raise endogenous GLP-1 two- to threefold, which explains their much smaller effect.
- Tirzepatide adds GIP receptor agonism and gives the largest HbA1c and weight falls of any current drug.
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Sources
- Mounjaro (tirzepatide) Australian Product Information, sections 4.5 and 4.6 (oral contraceptives; stop at least 1 month before a planned pregnancy)AU/NZmedsinfo.com.au (sponsor Product Information), October 2026
- Ozempic (semaglutide) Australian Product Information, section 4.6 (stop at least 2 months before a planned pregnancy)AU/NZmedsinfo.com.au (sponsor Product Information), November 2026
- Diabetes (Therapeutic Guidelines)AU/NZTherapeutic Guidelines Ltd, 2026
- Australian Medicines HandbookAU/NZAustralian Medicines Handbook Pty Ltd, 2026
- Medicine status: semaglutide (Wegovy), established cardiovascular disease with obesityAU/NZPharmaceutical Benefits Scheme, 2026
- Medicine status: tirzepatide, type 2 diabetesAU/NZPharmaceutical Benefits Scheme, 2026
- Management of hyperglycemia in type 2 diabetes, 2022. A consensus report by the ADA and EASDDiabetes Care 2022;45:2753-86, 2022
- Liraglutide and cardiovascular outcomes in type 2 diabetes (LEADER)Marso et al., N Engl J Med 2016;375:311-22, 2016
- Semaglutide and cardiovascular outcomes in patients with type 2 diabetes (SUSTAIN-6)Marso et al., N Engl J Med 2016;375:1834-44, 2016
- Semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT)Lincoff et al., N Engl J Med 2023;389:2221-32, 2023
- Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1)Jastreboff et al., N Engl J Med 2022;387:205-16, 2022
- Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus (SAVOR-TIMI 53)Scirica et al., N Engl J Med 2013;369:1317-26, 2013
- Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 2-5 June 2025 (semaglutide and NAION)European Medicines Agency, 2025
- Last updated
- 14 November 2026
What changed
- 14 November 2026 Personal emails, About story and Australian-style copy