Dipeptidyl Peptidase-4 Inhibitor Therapies in Type 2 Diabetes Management

Type 2 diabetes is characterised by progressive insulin secretory dysfunction and insulin resistance, which together drive chronic hyperglycaemia and associated microvascular and macrovascular complications. Incretin hormones—principally glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)—enhance postprandial insulin secretion, but are rapidly degraded by the serine protease dipeptidyl peptidase-4 (DPP-4). DPP-4 inhibitors (‘gliptins’) prolong incretin action, improving glycaemic control without weight gain or marked hypoglycaemia. Widely prescribed agents include sitagliptin, vildagliptin, saxagliptin, linagliptin and alogliptin. Used as monotherapy or added to metformin, sulfonylureas or insulin, DPP-4 inhibitors reduce glycated haemoglobin (HbA1c) by approximately 0.5–0.8 %, preserve pancreatic β-cell function and exhibit neutral cardiovascular effects. Their favourable tolerability and oral administration make them a mainstay in individualised treatment algorithms worldwide, particularly in patients at risk of hypoglycaemia or with renal impairment. Recent emphasis has focussed on their long-term effects on β-cell preservation, real-world cardiovascular safety and cost-effective formulations in combination therapies.

Research from Nature Portfolio

Recent meta-analytic evidence has clarified the mechanistic impact of DPP-4 inhibitors on pancreatic function. A comprehensive synthesis of randomised controlled trials demonstrated that both monotherapy and add-on regimens of DPP-4 inhibitors produce significant improvements in β-cell secretory capacity, as measured by the homoeostasis model assessment of β-cell function (HOMA-B). However, these agents exert minimal or no direct effect on insulin resistance indices (HOMA-IR), suggesting that their primary therapeutic benefit arises from incretin-mediated augmentation of insulin release rather than changes in peripheral insulin sensitivity.

Dipeptidyl Peptidase-4 Inhibitor Therapies in Type 2 Diabetes Management publication trend

The graph below shows the total number of articles in dipeptidyl peptidase-4 inhibitor therapies in type 2 diabetes management across all publications each year (not limited to Nature Index journals).

Technical terms

Dipeptidyl peptidase-4 (DPP-4): A serine protease that degrades incretin hormones, limiting postprandial insulin release.

Incretin hormones: Gut-derived peptides (GLP-1 and GIP) that stimulate glucose-dependent insulin secretion.

Glycated haemoglobin (HbA1c): A measure of average plasma glucose over the preceding 8–12 weeks, used to assess long-term glycaemic control.

HOMA-B: An index derived from fasting glucose and insulin concentrations to estimate β-cell secretory function.

HOMA-IR: An index derived from fasting glucose and insulin concentrations to estimate insulin resistance.

Bioequivalence: A demonstration that two formulations of a drug release the same active ingredient at the same rate and extent.

References

1. Effects of dipeptidyl peptidase-4 inhibitors on beta-cell function and insulin resistance in type 2 diabetes: meta-analysis of randomized controlled trials. Scientific Reports (2017).
2. Pharmacokinetic comparison of sitagliptin and metformin HCl extended-release tablets versus JANUMET® XR in healthy volunteers under fasting and fed conditions. Frontiers in Pharmacology (2023).
3. Benefits and risks of drug combination therapy for diabetes mellitus and its complications: a comprehensive review. Frontiers in Endocrinology (2023).
4. Efficacy and safety of saxagliptin in patients with type 2 diabetes: A systematic review and meta-analysis. PLOS ONE (2018).