OBJECTIVES: Our aim in this study was to compare severe hypoglycemia and all-cause mortality between insulin regimens in people with type 2 diabetes on insulin.
METHODS: This retrospective cohort study included individuals with type 2 diabetes who received a first insulin prescription from April 2007 to December 2018 in Manitoba, Canada. We used Cox proportional hazard regression models to compare risks and time to events for severe hypoglycemia and all-cause mortality among insulin regimens, adjusting for covariates.
RESULTS: A total of 21,512 individuals were included in the study, with 1,156 (5.4%) individuals experiencing a severe hypoglycemic episode and 3,562 (16.6%) dying during the study period. When compared with long-acting insulin alone, short-acting, intermediate- plus short-acting, long- plus short-acting, and premixed insulins were associated with severe hypoglycemia. However, after removing individuals who had never been prescribed a noninsulin antihyperglycemic medication, short-acting insulin was no longer associated with severe hypoglycemia, with the adjusted hazard ratio (HR) decreasing from 1.99 (95% confidence interval [CI] 1.44 to 2.74) for the entire cohort to 1.13 (95% CI 0.63 to 2.04). When compared with long-acting insulin, short-acting insulin alone and premixed insulin were associated with a higher all-cause mortality in both the main analysis (adjusted HR 2.36 [95% CI 2.06 to 2.72] and 1.17 [95% CI 1.04 to 1.31], respectively) and the analysis that excluded those individuals never prescribed a noninsulin antihyperglycemic agent.
CONCLUSIONS: Severe hypoglycemia is common in those with type 2 diabetes on insulin. Several insulin regimens were associated with severe hypoglycemia and/or all-cause mortality. However, additional research is required to determine whether this association is causal, or indicative of insulin regimen differences due to residual confounders, such as diabetes severity, prognosis, or health literacy.