GLP-1 Receptor Agonist-Based Prandial Insulin De-Intensification in Outpatients With Type 2 Diabetes Receiving Basal-Bolus Insulin Therapy or Multiple Daily Injections: A Systematic Review and Meta-Analysis of Randomised Controlled Trials

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• Picked for Internal Medicine (top studies of the week, 20 September 2026): GLP‑1RA de‑intensification maintains HbA1c while reducing weight

Abstract

AIMS: This systematic review and meta-analysis aimed to compare GLP-1 receptor agonist (GLP-1RA)-based prandial insulin de-intensification with continued basal-bolus insulin therapy (BBI) or multiple daily injections (MDI) in adult outpatients with type 2 diabetes receiving established BBI/MDI at randomisation. MATERIALS AND METHODS: PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL) and Web of Science were searched for randomised controlled trials enrolling adult outpatients with type 2 diabetes receiving established BBI/MDI at randomisation. Eligible trials compared a GLP-1RA-based strategy involving protocol-directed withdrawal, replacement or substantial reduction of scheduled prandial insulin while maintaining basal insulin versus continued BBI/MDI therapy. The primary outcome was change in HbA1c. Secondary outcomes included changes in body weight, total daily insulin dose (TDD), hypoglycaemia and de-intensification-related outcomes. RESULTS: Seven randomised controlled trials involving 1332 participants were included. Compared with continued BBI/MDI therapy, GLP-1RA-based prandial insulin de-intensification was not associated with a significant difference in HbA1c change (mean difference [MD] -0.08 percentage points, 95% confidence interval [CI] -0.28 to 0.12; p = 0.391). The de-intensification strategy was associated with reductions in body weight (MD -4.94 kg, 95% CI -7.37 to -2.51; p = 0.003) and total daily insulin dose (MD -33.32 U/day, 95% CI -52.23 to -14.41; p = 0.006). The risk of experiencing at least one hypoglycaemic event was lower with GLP-1RA-based de-intensification (risk ratio [RR] 0.76, 95% CI 0.66 to 0.87; p = 0.007). CONCLUSIONS: In adults with type 2 diabetes receiving established BBI/MDI therapy, GLP-1RA-based prandial insulin de-intensification was associated with maintenance of short-term glycaemic control while reducing body weight and total daily insulin requirements. A potential reduction in hypoglycaemia remains uncertain. This strategy may represent an option for treatment optimisation in appropriately selected patients receiving intensive insulin therapy; however, further studies are needed to determine its long-term sustainability and optimal implementation.

Abstract as published, via PubMed.