OPTIMIZATION OF HYPERGLYCEMIA TREATMENT INTENSIFICATION FOR PATIENTS WITH TYPE 2 DIABETES

Purpose: To estimate the optimal time to intensify treatment for hyperglycemia in patients with type 2 diabetes who have initiated metformin.

Method: We used a Markov decision process (MDP) model to determine optimal sequence and time to intensify treatment using sulfonylurea and insulin. Health states included risk factors such as Hemoglobin A1c (A1c), blood pressure and cholesterol. A1c was defined by four Markov states, starting at age 40 (A1c≤7%, 7%<A1c≤8%, 8%<A1c≤9%, A1c>9%), with A1c values increasing linearly with respect to age at a rate of 0.07% per year. Transition probabilities and the medication effects were estimated from electronic medical records, and once a medication was initiated, A1c was reduced according to the estimated medication’s effect. The probabilities of having severe hypoglycemia, macro- and micro-vascular events (major complications) were taken from the United Kingdom Prospective Diabetes Study. Medication disutilities were based on secondary sources.  One-way sensitivity analysis was performed by varying the annual probability of severe hypoglycemia caused by insulin from 1% to 3% (base case 1.96%).  The goal of the model was to identify the optimal time to intensify such that quality-adjusted life years (QALYs) prior to the first major complication could be maximized.  

Result: For the base case the mean time to intensification with a sulfonylurea was 6.3 and 6.8 years after initiating metformin, and the mean time to initiate insulin after beginning sulfonylurea was 17.7 and 23 years, for male and female patients, respectively. When the probability of hypoglycemia was reduced to 1%, some patients intensified with sulfonylurea first and some with insulin first, depending on their A1c level. The mean time to a first intensification was 6.4 and 7.1 years for male and female patients, respectively. Assuming a probability of hypoglycemia of 3%, all patient intensified with sulfonylurea first and the mean time to intensify was 6.2 and 6.7 years for male and female patients, respectively.

Conclusion: Given the criteria of maximizing QALYs, mean time to intensify treatment may be longer than secondary failure times reported in the literature. The optimal start time for insulin is significantly affected by the risk of hypoglycemia.