Abstract
BACKGROUND: Current guidelines recommend baseline insulin as the standard treatment for most people hospitalised with type 2 diabetes (PWT2D). However, they generally discourage the use of sodium–glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists due to safety concerns and a lack of randomised evidence. We aim to assess primarily safety, and secondarily, effectiveness of non-insulin glucose-lowering therapy for inpatients, as implemented within a structured start-stop clinical practice guideline. METHODS: We conducted a 9-month pragmatic prospective cohort study including PWT2D adults who were admitted to the medical and surgical wards of a tertiary hospital. Participants were managed either on oral antidiabetic drugs (with or without insulin) under a start–stop protocol (Group A) or with insulin-only therapy (Group B). The primary outcome was safety, defined as severe adverse events (level 2–3 hypoglycaemia or diabetic ketoacidosis). Secondary outcomes included median daily capillary glucose and glycaemic variability. Hospital stay, intensive care unit admission and mortality were exploratory outcomes. Multivariable logistic regression and propensity score matching were employed to adjust for confounding factors. RESULTS: A total of 979 participants were included in the study: 582 in the Group A and 397 in the Group B. Seventy-three severe adverse events occurred, primarily hypoglycaemia. Non-insulin therapy was independently associated with a lower risk of severe adverse events (aOR 0.53 [95%CI 0.29–0.97]), and these results remained consistent after propensity score matching (OR 0.31 [95%CI 0.15–0.61]). The Group A had a lower median daily glucose level (153 mg/dL vs. 179 mg/dL; p < 0.001), lower glycaemic variability and a shorter hospital stay (5 days vs. 7 days; p < 0.001). No differences were observed in intensive care unit admission or mortality. CONCLUSIONS: In real hospital settings, the use of non-insulin therapies, predominantly SGLT2 inhibitors and GLP-1 RAs guided by a start-stop CPG, was associated with a safe and effective glycemic management profile. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12933-026-03156-6.