Quantifying the Trade-off Between Improved Glycemic Control and Severe Hypoglycemia Risk in Patients with Type 1 Diabetes: A Health Economic Analysis in the Uk

Abstract

The Diabetes Control and Complications Trial (DCCT) established that intensive glycemic control results in improved long-term microvascular outcomes in patients with type 1 diabetes (T1D). The DCCT also, however, reported a threefold increase in severe hypoglycemia rates in intensively-managed patients relative to conventionally-managed patients. The present analysis used modern computer simulation techniques to quantify this trade-off between glycemic control and severe hypoglycemia risk. A complication cost analysis was conducted with the PRIME Diabetes Model, a long-term, externally audited and validated patient-level simulation model of T1D. A Poisson regression model from the DCCT was used to establish the expected glycated hemoglobin (HbA1c) levels attained in populations with average severe hypoglycemia rates of 0.4 and 0.6 events per year. These scenarios were used as the basis of the analysis, modeling incremental costs associated with diabetes complication incidence in the two scenarios over patient lifetimes. Costs were reported in 2016 pounds sterling, with future costs and effects discounted at 3.5% per annum. Populations of patients with average severe hypoglycemia rates of 0.4 and 0.6 events per year would be anticipated to have mean HbA1c levels of 8.54% and 7.38% respectively based on DCCT data. The increased hypoglycemia (low HbA1c) scenario improved quality-adjusted life expectancy relative to the lower hypoglycemia rate scenario, yielding an improvement of 0.30 quality-adjusted life years, despite an increase in cumulative incidence of hypoglycemia-related mortality from 0.78% to 0.91%. Average complication costs decreased by GBP 928 from GBP 23,632 to GBP 22,703 with improved glycemic control. The present analysis demonstrated the utility of computer simulation models such as the PRIME Diabetes Model in evaluating treatment guidelines. The analysis showed that the trade-offs of increased hypoglycemia and hypoglycemia-related mortality are more than offset by improvements in quality of life and reductions in cost at the population level.