Incretin-based injectable strategies versus intensified insulin for treatment intensification and simplification in type 2 diabetes: a systematic review and meta-analysis.

Authors

Talha Mahmood, Ioanna Myrtziou, Ioannis Kanakis

Published in

Journal of diabetes and metabolic disorders. Volume 25. Issue 2. Pages 270. Epub Sep 26, 2026.

Abstract

Prandial insulin intensification in Type 2 Diabetes (T2D) improves glycaemia but increases regimen complexity, weight gain, and hypoglycaemia risk. Our aim was to evaluate if Incretin-based injectable strategies offer a lower-burden alternative across intensification and simplification pathways.
PubMed/MEDLINE, CENTRAL, Scopus, and ClinicalTrials.gov were searched to November 2025 for Randomised Controlled Trials (RCT) comparing incretin-based injectable regimens with intensified insulin strategies in adults with T2D. Primary outcomes were HbA1c change and trial-defined hypoglycaemia. Secondary outcomes included body weight, HbA1c target achievement, severe hypoglycaemia, insulin dose, gastrointestinal adverse events, and adverse-event withdrawals. Random or fixed-effects models were applied where appropriate, with subgroup analyses by regimen and by intensification versus simplification design.
Eighteen RCTs were included. Incretin-based regimens significantly reduced HbA1c as compared to intensified insulin (MD -0.19%, 95% CI: -0.34 to -0.05, P = 0.01) and also increased HbA1c target achievement (RR 1.27, 95% CI: 1.05 to 1.54, P = 0.01). Effects differed by regimen and design: tirzepatide produced the largest HbA1c reduction, fixed-ratio or once-weekly combination regimens showed similar HbA1c efficacy, and simplification trials generally preserved glycaemic control. Incretin-based regimens decreased trial-defined hypoglycaemia (RR 0.48, 95% CI: 0.35 to 0.66, P = 0.00001), severe hypoglycaemia (RR 0.32, 95% CI: 0.19 to 0.51, P = 0.00001), and body weight (MD -4.65 kg, 95% CI: -5.85 to -3.44, P = 0.00001). Gastrointestinal adverse events were more frequent with incretin-based regimens.
Incretin-based injectable strategies are a favourable alternative to intensified insulin when hypoglycaemia, weight gain, and treatment burden are priorities, but benefits differ between intensification and simplification settings.
The online version contains supplementary material available at https://doi.org/10.1007/s40200-026-02089-x.

PMID:
42802751
Bibliographic data and abstract were imported from PubMed on 28 Sep 2026.

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