Glucose-lowering with exogenous insulin monotherapy in type 2 diabetes: dose association with all-cause mortality, cardiovascular events, and incident cancer
To evaluate the association between insulin exposure and all-cause mortality, incident major adverse cardiovascular events (MACE), and incident cancer in people with type 2 diabetes treated with insulin monotherapy.
Materials and methods:
For this retrospective study, people with type 2 diabetes who progressed to insulin monotherapy from 2000 were identified from the UK Clinical Practice Research Datalink. The risks of progression to serious adverse outcomes—all-cause mortality, major adverse cardiac events, and cancer—were compared using Cox proportional hazards models. In the main analysis, insulin exposure was introduced into the model as prescribed international units per kilogram per day, as a cumulative, continuous, annually updated, time-dependent covariable.
6,484 subjects with type 2 diabetes who progressed to treatment with insulin monotherapy from 2000 onwards were followed up for a mean of 3.3 years. The number of events was as follows: deaths, 1,110; incident MACE, 342; incident cancers, 382. Unadjusted event rates were 61.3 deaths per 1,000 person years, 26.4 incident MACE per 1,000 person years, and 24.6 incident cancers per 1,000 person years. The adjusted hazard ratios in relation to one unit increases in insulin dose were 1.54 (95% CI 1.32–1.78) for all-cause mortality, 1.37 (1.05–1.81) for MACE, and 1.35 (1.04–1.75) for cancer.
There was an association between increasing exogenous insulin dose and increased risk of all-cause mortality, cancer and MACE in people with type 2 diabetes. Limitations of observational studies mean that this should be further investigated using an interventional study design.