Cardiovascular events and all-cause mortality with insulin versus glucagon-like peptide-1 analogue in type 2 diabetes

Objectives To analyse time to cardiovascular events and mortality in patients with type 2 diabetes (T2D) who received treatment intensification with insulin or a glucagon-like peptide-1 (GLP-1ar) analogue following dual therapy failure with metformin (MET) and sulphonylurea (SU). Methods A retrospective cohort study was conducted in 2003 patients who were newly treated with a GLP-1ar or insulin following dual therapy (MET+SU) failure between 2006 and 2014. Data were sourced from The Health Improvement Network database. Risks of major adverse cardiovascular events (MACE) (non-fatal myocardial infarction, non-fatal stroke and all-cause mortality) were compared between MET+SU+insulin (N=1584) versus MET+SU+GLP-1ar (N=419). Follow-up was for 5years (6614 person-years). Propensity score matching analysis and Cox proportional hazard models were employed. Results Mean age was 52.814.1years. Overall, the number of MACE was 231 vs 11 for patients who added insulin versus GLP-1ar, respectively (44.5 vs 7.7 per 1000-person-years adjusted HR (aHR): 0.27; 95% CI 0.14 to 0.53; p<0.0001). Insulin was associated with significant increase in weight compared with GLP-1ar (1.78 vs -3.93kg; p<0.0001) but haemoglobin A1c reduction was similar between both treatment groups (-1.29 vs -0.98; p=0.156). In a subgroup analysis of obese patients (body mass index >30kg/m(2)) there were 84 vs 11 composite outcomes (38.6 vs 8.1 per 1000 person-years; aHR: 0.31; 95% CI 0.16 to 0.61; p=0.001) in the insulin and GLP-1ar groups, respectively. Conclusions In this cohort of obese people with T2DM, intensification of dual oral therapy by adding GLP-1ar analogue is associated with a lower MACE outcome in routine clinical practice, compared with adding insulin therapy as the third glucose-lowering agent.