A transparent machine learning algorithm uncovers HbA1c patterns associated with therapeutic inertia in patients with type 2 diabetes and failure of metformin monotherapy

Aims: This study aimed to identify and categorize the determinants influencing the intensification of therapy in Type 2 Diabetes (T2D) patients with suboptimal blood glucose control despite metformin monotherapy. Methods: Employing the Logic Learning Machine (LLM), an advanced artificial intelligence system, we scrutinized electronic health records of 1.5 million patients treated in 271 diabetes clinics affiliated with the Italian Association of Medical Diabetologists from 2005 to 2019. Inclusion criteria comprised patients on metformin monotherapy with two consecutive mean HbA1c levels exceeding 7.0%. The cohort was divided into "inertia-NO" (20,067 patients with prompt intensification) and "inertia-YES" (13,029 patients without timely intensification). Results: The LLM model demonstrated robust discriminatory ability among the two groups (ROC-AUC = 0.81, accuracy = 0.71, precision = 0.80, recall = 0.71, F1 score = 0.75). The main novelty of our results is indeed the identification of two main distinct subtypes of therapeutic inertia. The first exhibited a gradual but steady HbA1c increase, while the second featured a moderate, non-uniform rise with substantial fluctuations. Conclusions: Our analysis sheds light on the significant impact of HbA1c levels over time on therapeutic inertia in patients with T2D, emphasizing the importance of early intervention in the presence of specific HbA1c patterns.