Achieving Good Metabolic Control Without Weight Gain with the Systematic Use of GLP-1-RAs and SGLT-2 Inhibitors in Type 2 Diabetes: A Machine-learning Projection Using Data from Clinical Practice.

Purpose: Recently, the 2022 American Diabetes Association and European Association for the Study of Diabetes (ADA-EASD) consensus report stressed the importance of weight control in the management of patients with type 2 diabetes; weight control should be a primary target of therapy. This retrospective analysis evaluated, through an artificial-intelligence (AI) projection of data from the AMD Annals database-a huge collection of most Italian diabetology medical records covering 15 years (2005-2019)-the potential effects of the extended use of sodium-glucose co-transporter 2 inhibitors (SGLT-2is) and of glucose-like peptide 1 receptor antagonists (GLP-1-RAs) on HbA and weight.

Methods: Data from 4,927,548 visits in 558,097 patients were retrospectively extracted using these exclusion criteria: type 1 diabetes, pregnancy, age >75 years, dialysis, and lack of data on HbA or weight. The analysis revealed late prescribing of SGLT-2is and GLP-1-RAs (innovative drugs), and considering a time frame of 4 years (2014-2017), a paradoxic greater percentage of combined-goal (HbA <7% and weight gain <2%) achievement was found with older drugs than with innovative drugs, demonstrating aspects of therapeutic inertia. Through a machine-learning AI technique, a "what-if" analysis was performed, using query models of two outcomes: (1) achievement of the combined goal at the visit subsequent to a hypothetical initial prescribing of an SGLT-2i or a GLP-1-RA, with and without insulin, selected according to the 2018 ADA-EASD diabetes recommendations; and (2) persistence of the combined goal for 18 months. The precision values of the two models were, respectively, sensitivity, 71.1 % and 69.8%, and specificity, 67% and 76%.

Findings: The first query of the AI analysis showed a great improvement in achievement of the combined goal: 38.8% with prescribing in clinical practice versus 66.5% with prescribing in the "what-if" simulation. Addressing persistence at 18 months after the initial achievement of the combined goal, the simulation showed a potential better performance of SGLT-2is and GLP-1-RAs with respect to each antidiabetic pharmacologic class or combination considered.

Implications: AI appears potentially useful in the analysis of a great amount of data, such as that derived from the AMD Annals. In the present study, an LLM analysis revealed a great potential improvement in achieving metabolic targets with SGLT-2i and GLP-1-RA utilization. These results underscore the importance of early, timely, and extended use of these new drugs.