Comparing Outcomes of Type 2 Diabetics Using Human Versus Analogue Insulin

Romain Neugebauer, PhD

A new study is uncovering more about the potential impact of human versus analogue insulins on mortality and major cardiovascular events (MACE) in patients with type 2 diabetes (T2D).

The study, which examined more than 125,000 patients with T2D found there was little difference in rates of MACE, cardiovascular disease mortality, and overall mortality based on insulin type among insulin-naive adults.

With a lack of studies examining the potential differences between outcomes when using human or analogue insulins, investigators from Healthcare Services Research Network conducted a study across 4 US sites to assess from 2000 through 2013. A total of 127,600 adults between the ages of 21 and 89 years old with T2D were included in the retrospective cohort study.

More than 1.08 million patients were included in the investigators’ original search. After the application of inclusion criteria, which mandated all patients be insulin-naive, 2 separate cohorts were created for the study. In total, 18,928 patients were included in the analogue insulin group and 108,672 were included in the human insulin group.

Investigators assessed 5 time-to-event outcomes as part of their analysis. These included acute myocardial infarction, stroke or cerebrovascular accident, hospitalization for congestive heart failure, overall mortality, and mortality from cardiovascular disease.

The team used marginal structural modeling (MSM) with inverse probability weighting was used to compare event-free survival in a operate per-protocol analyses. Hazard ratios, both adjusted and unadjusted, and cumulative risk differences were based on logistic MSM parameterizations for counterfactual hazards. Additionally, propensity scores were estimated using a machine learning approach based on 3 nested covariate adjustment sets.

Investigators noted multiple differences in baseline characteristics between the 2 study arms. The analogue insulin group was slightly younger (58.8 [13.2] vs 59.5 [12.5] years) and had a higher rate of comorbidities—including coronary artery disease (18.7% vs 16.1%), cerebrovascular accident (2.2% vs 1.6%), and congestive heart failure (7.6% vs 6.5%). Investigators pointed out mean HbA1c levels, blood pressure, and smoking rates were similar between both groups.

Overall, the mean age of study participants was 59.4 (12.6) years, 53.8% were men, and the mean BMI was 32.3 (7.1). A total of 5464 deaths, 1729 acute myocardial infarctions, 1301 cerebrovascular accidents, and 3082 hospitalizations for congestive heart failure occurred among the 127,600 participants.

When comparing rates of outcomes between the 2 study arms, there were no differences in adjusted hazard ratios for analogue insulin compared to human insulin. The observed hazard ratios were 1.15 (95% CI, 0.97-1.34) for overall mortality, 1.26 (0.86-1.66) for cardiovascular disease mortality, 1.11 (0.77-1.45) for myocardial infarction, 1.30 (0.81-1.78) for cerebrovascular accident, and 0.93 (0.75-1.11) for congestive heart failure hospitalization.

Based on the results of their analyses, investigators suggest those who initiate and continue treatment with human or analogue insulins experienced had similar observed rates of MACE, cardiovascular disease mortality, and overall mortality.

This study, titled “Comparison of Mortality and Major Cardiovascular Events Among Adults With Type 2 Diabetes Using Human vs Analogue Insulins,” is published online in JAMA Network Open.