Effective Treatment Recommendations for Type 2 Diabetes Management Using Reinforcement Learning: Treatment Recommendation Model Development and Validation
Authors: Sun Xingzhi , Bee Yong Mong , Lam Shao Wei , Liu Zhuo , Zhao Wei , Chia Sing Yi , Abdul Kadir Hanis , Wu Jun Tian , Ang Boon Yew , Liu Nan , Lei Zuo , Xu Zhuoyang , Zhao Tingting , Hu Gang , Xie Guotong 
Published: July 2021

Background
Type 2 diabetes mellitus (T2DM) and its related complications represent a growing economic burden for many countries and health systems. Diabetes complications can be prevented through better disease control, but there is a large gap between the recommended treatment and the treatment that patients actually receive. The treatment of T2DM can be challenging because of different comprehensive therapeutic targets and individual variability of the patients, leading to the need for precise, personalized treatment.

Objective
The aim of this study was to develop treatment recommendation models for T2DM based on deep reinforcement learning. A retrospective analysis was then performed to evaluate the reliability and effectiveness of the models.

Methods
The data used in our study were collected from the Singapore Health Services Diabetes Registry, encompassing 189,520 patients with T2DM, including 6,407,958 outpatient visits from 2013 to 2018. The treatment recommendation model was built based on 80% of the dataset and its effectiveness was evaluated with the remaining 20% of data. Three treatment recommendation models were developed for antiglycemic, antihypertensive, and lipid-lowering treatments by combining a knowledge-driven model and a data-driven model. The knowledge-driven model, based on clinical guidelines and expert experiences, was first applied to select the candidate medications. The data-driven model, based on deep reinforcement learning, was used to rank the candidates according to the expected clinical outcomes. To evaluate the models, short-term outcomes were compared between the model-concordant treatments and the model-nonconcordant treatments with confounder adjustment by stratification, propensity score weighting, and multivariate regression. For long-term outcomes, model-concordant rates were included as independent variables to evaluate if the combined antiglycemic, antihypertensive, and lipid-lowering treatments had a positive impact on reduction of long-term complication occurrence or death at the patient level via multivariate logistic regression.

Results
The test data consisted of 36,993 patients for evaluating the effectiveness of the three treatment recommendation models. In 43.3% of patient visits, the antiglycemic medications recommended by the model were concordant with the actual prescriptions of the physicians. The concordant rates for antihypertensive medications and lipid-lowering medications were 51.3% and 58.9%, respectively. The evaluation results also showed that model-concordant treatments were associated with better glycemic control (odds ratio [OR] 1.73, 95% CI 1.69-1.76), blood pressure control (OR 1.26, 95% CI, 1.23-1.29), and blood lipids control (OR 1.28, 95% CI 1.22-1.35). We also found that patients with more model-concordant treatments were associated with a lower risk of diabetes complications (including 3 macrovascular and 2 microvascular complications) and death, suggesting that the models have the potential of achieving better outcomes in the long term.

Conclusions
Comprehensive management by combining knowledge-driven and data-driven models has good potential to help physicians improve the clinical outcomes of patients with T2DM; achieving good control on blood glucose, blood pressure, and blood lipids; and reducing the risk of diabetes complications in the long term.