Treatment Intensification Strategies and Metabolic Outcomes in Individuals With Type 2 Diabetes on GLP-1 RA Therapy

Context Despite the efficacy of glucagon-like peptide 1 receptor agonists (GLP-1 RAs), many patients with type 2 diabetes (T2D) require additional therapy to achieve glycated hemoglobin (HbA1c) targets. Few studies have explored real-world outcomes following GLP-1 RA failure. Objective This analysis evaluates different intensification approaches, timing, and outcomes in patients with T2D on GLP-1 RAs. Methods This retrospective cohort study was based on the AMD Annals database. From 191 041 patients on GLP-1 RAs between 2010 and 2022, individuals receiving a first therapeutic intensification were selected. Patients were stratified by intensification strategy; baseline characteristics were compared alongside HbA1c and weight changes at 6 and 12 months. Results Among the 37 198 intensified patients, the majority received oral antihyperglycemic drugs (OADs), particularly those with higher body mass index, lower HbA1c, and shorter disease duration. Basal insulin (BI) was mainly added in those with higher HbA1c (8.9%) and longer diabetes. Intensification with BI or switch to fixed ratio combinations (FRCs) yielded the greatest HbA1c reduction (-0.92 and -0.85%; P < .001) and weight neutrality, whereas OADs led to a higher target achievement rate (36% with HbA1c < 7%) and persistent weight loss. Switching to BB was reserved for more complicated patients and it was associated with weight gain (+2.9 kg; P < .001) and lower target achievement rate (16.8% HbA1c < 7%). Suboptimal insulin titration was observed across all strategies. Conclusion Adding OADs or BI/FRCs to GLP-1 RAs are optimal intensification strategies to provide glycemic control while avoiding weight gain. Target achievement rates are poor in individuals switched to insulin therapy. Therapeutic inertia remains a critical issue in clinical practice.