Use of Analog and Human Insulin in a European Hemodialysis Cohort With Type 2 Diabetes: Associations With Mortality, Hospitalization, MACE, and Hypoglycemia

Abstract

Rationale & objective: Poor glycemic control may contribute to the high mortality rate in patients with type 2 diabetes receiving hemodialysis. Insulin type may influence glycemic control, and its choice may be an opportunity to improve outcomes. This study assessed whether treatment with analog insulin compared with human insulin is associated with different outcomes in people with type 2 diabetes and kidney failure receiving hemodialysis.

Study design: Retrospective cohort study.

Setting & participants: People in the Analyzing Data, Recognizing Excellence and Optimizing Outcomes (AROii) study with kidney failure commencing hemodialysis and type 2 diabetes being treated with insulin within 288 dialysis facilities between 2007 and 2009 across 7 European countries. Study participants were followed for 3 years. People with type 1 diabetes were excluded using an established administrative data algorithm.

Exposure: Treatment with an insulin analog or human insulin.

Outcome: All-cause mortality, major adverse cardiovascular events (MACE), all-cause hospitalization, and confirmed hypoglycemia (blood glucose<3.0mmol/L sampled during hemodialysis).

Analytical approach: Inverse probability weighted Cox proportional hazards models to estimate hazard ratios for analog insulin compared with human insulin.

Results: There were 713 insulin analog and 733 human insulin users. Significant variation in insulin type by country was observed. Comparing analog with human insulin at 3 years, the percentage of patients experiencing end points and adjusted hazard ratios (AHR) were 22.0% versus 31.4% (AHR, 0.808 [95% CI, 0.66-0.99], P=0.04) for all-cause mortality, 26.8% versus 35.9% (AHR, 0.817 [95% CI, 0.68-0.98], P=0.03) for MACE, and 58.2% versus 75.0% (AHR, 0.757 [95% CI, 0.67-0.86], P<0.001) for hospitalization. Hypoglycemia was comparable between insulin types at 14.1% versus 15.0% (AHR, 1.169 [95% CI, 0.80-1.72], P=0.4). Consistent strength and direction of the associations were observed across sensitivity analyses.

Limitations: Residual confounding, lack of more detailed glycemia data.

Conclusions: In this large multinational cohort of people with type 2 diabetes and kidney failure receiving maintenance hemodialysis, treatment with analog insulins was associated with better clinical outcomes when compared with human insulin.

Plain-language summary: People with diabetes who are receiving dialysis for kidney failure are at high risk of cardiovascular disease and death. This study uses information from 1,446 people with kidney failure from 7 European countries who are receiving dialysis, have type 2 diabetes, and are prescribed either insulin identical to that made in the body (human insulin) or insulins with engineered extra features (insulin analog). After 3 years, fewer participants receiving analog insulins had died, had been admitted to the hospital, or had a cardiovascular event (heart attack, stroke, heart failure, or peripheral vascular disease). These findings suggest that analog insulins should be further explored as a treatment leading to better outcomes for people with diabetes on dialysis.

Keywords: Hemodialysis; insulin; major adverse cardiovascular events; mortality; type 2 diabetes.