Patients with type 2 diabetes taking exogenous insulin could be at increased risk for death from all causes, major adverse cardiovascular events and cancer with increasing dosage, according to research published in Diabetes, Obesity and Metabolism.
“We found that there was an association between the dose of prescribed insulin and increased risk of all-cause mortality,” the researchers wrote. “A statistically significant association with major adverse cardiovascular events and cancer was also observed.”
Sarah E. Holden, a PhD student at Cardiff University School of Medicine, United Kingdom, along with Craig Currie, PhD, and colleagues wrote that the findings add to ongoing concerns regarding insulin use to treat the chronic disease but warrant additional investigation.
“Limitations associated with both the estimation of insulin dose and also the retrospective observational nature of the study mean that this hypothesis should be tested using an interventional study design,” they wrote.
Using the UK Clinical Practice Research Datalink, the researchers identified 6,484 patients (mean age at baseline, 64 years) with type 2 diabetes who progressed to insulin monotherapy from 2000 onward and followed them for an average of 3.3 years.
Risks of progression to serious adverse outcomes — all-cause mortality, incident major adverse cardiovascular events (MACE) and incident cancer — were compared using Cox proportional hazards models.
Insulin exposure as a cumulative, continuous, annually updated, time-dependent covariable was introduced into the model as prescribed international units per kilogram per day; results were reported in four patient groups, defined by the doses ranging from <0.5 units per kilogram of bodyweight per day, up to doses >1.5 units.
The analysis of medical history showed 1,110 deaths, 342 MACE and 382 incident cancers. Unadjusted event rates, per 1,000 person-years, were 61.3 deaths, 26.4 incident MACE and 24.6 incident cancers. Adjusted HRs, relative to 1-unit increases in insulin dose, were 1.54 (95% CI, 1.32-1.78) for all-cause mortality, 1.37 (95% CI, 1.05-1.81) for MACE and 1.35 (95% CI, 1.04-1.75) for cancer.
“When compared to patients who received doses of less than 0.5 units, our findings indicate that patients receiving doses of between 1 to 1.5 units and more than 1.5 units were associated with a much greater death rate over time,” Currie said in a press release.
The researchers noted that the potential risks associated with insulin therapy should be considered in the context of its benefits for glucose control, inherently reducing the risk for microvascular events, and that the findings do not relate to type 1 diabetes.
Retrospective observational studies can only show associations with events, they said.
“What this study does show is a need for prospective randomized controlled trials to investigate the cause behind these patterns to provide conclusive evidence as to the real effect insulin is having on the thousands of patients who rely on glucose-controlling medication,” Currie said in the release.
Disclosure: Please see study for full list of disclosures.