Incretin-Based Therapeutics for Type 2 Diabetes Management

Incretin-based therapies exploit the glucose-dependent actions of gut-derived hormones to improve glycaemic control, promote weight loss and confer cardiovascular benefits in type 2 diabetes. Two principal incretins, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are secreted after nutrient intake and augment insulin secretion while suppressing glucagon release. Pharmacological strategies include GLP-1 receptor agonists, which mimic and prolong the effects of endogenous GLP-1, and dipeptidyl peptidase-4 (DPP-4) inhibitors, which prevent rapid hormone degradation. The introduction of long-acting GLP-1 analogues has transformed clinical practice by enabling once-daily or once-weekly dosing, improving adherence and reducing the risk of hypoglycaemia. More recently, dual agonists targeting both GLP-1 and GIP receptors have emerged, offering synergistic effects on weight reduction and glycaemic stability. Incretin therapies now extend beyond glucose lowering to reduce cardiovascular events, support renal function and attenuate low-grade inflammation. Their flexible formulations, including injectable and oral preparations, allow tailored regimens across diverse patient populations, addressing global challenges in diabetes care and comorbidity management.

Research from Nature Portfolio

Long-term outcome trials of a weekly GLP-1 analogue have demonstrated sustained weight loss and improved anthropometric measures in individuals with overweight or obesity, many of whom were at elevated cardiovascular risk. Over four years, treatment achieved mean weight reductions exceeding 10 %, waist-to-height ratios fell by nearly 7 %, and the incidence of serious adverse events declined across all body mass index categories. Tolerability remains high, with gastrointestinal complaints as the principal cause of discontinuation. These findings reinforce the role of potent GLP-1 receptor agonism, not only in glycaemic regulation but also in durable weight management and cardiovascular risk mitigation.

Incretin-Based Therapeutics for Type 2 Diabetes Management publication trend

The graph below shows the total number of articles in incretin-based therapeutics for type 2 diabetes management across all publications each year (not limited to Nature Index journals).

Technical terms

Incretin hormone: Gut-derived peptide that enhances insulin secretion in response to oral glucose.

GLP-1 receptor agonist (GLP-1RA): Synthetic analogue of glucagon-like peptide-1 designed to resist enzymatic degradation and prolong receptor activation.

DPP-4 inhibitor: Small-molecule drug that blocks dipeptidyl peptidase-4, the enzyme responsible for inactivating endogenous incretins.

GIP: Glucose-dependent insulinotropic polypeptide, an incretin that stimulates insulin release and modulates lipid metabolism.

Dual GIP/GLP-1 receptor agonist: Molecule engineered to activate both GIP and GLP-1 receptors, offering combined metabolic benefits.

References

1. Glucagon-like peptide-1 receptor: mechanisms and advances in therapy. Signal Transduction and Targeted Therapy (2024).
2. Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial. Nature Medicine (2024).
3. The Discovery and Development of Liraglutide and Semaglutide. Frontiers in Endocrinology (2019).
4. How May GIP Enhance the Therapeutic Efficacy of GLP-1?. Trends in Endocrinology and Metabolism (2020).
5. Anti‐Inflammatory Effects of GLP‐1‐Based Therapies beyond Glucose Control. Mediators of Inflammation (2016).