Association of glucose-lowering drugs with incident stroke and transient ischaemic attacks in primary care patients with type 2 diabetes: disease analyzer database

AIMS: Previous observational studies on glucose-lowering drugs and risk of stroke in type 2 diabetes yielded conflicting results. The aim was to examine the association of glucose-lowering drugs with incident stroke and transient ischaemic attacks (TIA) in newly diagnosed type 2 diabetes. METHODS: We conducted a retrospective cohort analysis of the disease analyzer, which comprises a representative panel of 1248 general and internal medicine practices throughout Germany (01/2000–12/2019: 9.8 million patients). Incident non-fatal stroke/TIA was defined based on ICD-10 codes (I63, I64; G45) in newly diagnosed type 2 diabetes. Cox regression models were fitted to obtain hazard ratios (HR; 95%CI) for stroke/TIA adjusting for potential confounders (age, sex, health insurance, coronary heart disease, myocardial infarction, heart failure, polyneuropathy, blood pressure, eGFR) and anthropometric and metabolic intermediators (BMI, HbA1c, HDL- and LDL-cholesterol, triglycerides, lipid-lowering drugs). RESULT: 312,368 persons with newly diagnosed type 2 diabetes without previous stroke/TIA (mean age: 64 years; 52% males) were included. There were 16,701 events of non-fatal stroke/TIA corresponding to an incidence rate of 9.3 (95%CI 9.1–9.4) per 1000 person-years. Using Cox regression, adjusted HR for stroke/TIA (per 1 year of treatment) of 0.59 (0.54–0.64) for SGLT2 inhibitors and of 0.79 (0.74–0.85) for GLP-1 receptor agonists were estimated. DPP-4 inhibitors (0.84; 0.82–0.86), metformin (0.90; 0.89–0.91), insulin (0.92; 0.91–0.93) and sulfonylureas (0.98; 0.96–0.99) also showed moderately reduced HR for stroke/TIA. Sex-specific regression analyses yielded similar results (HR). CONCLUSIONS: Treatment with SGLT2 inhibitors or GLP-1 receptor agonists might reduce non-fatal stroke/TIA in persons with newly diagnosed type 2 diabetes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00592-022-01943-7.