Related Experiment Video
Updated: May 15, 2025

A Zebrafish Model of Diabetes Mellitus and Metabolic Memory
Published on: February 28, 2013
Treatment Intensification Strategies and Metabolic Outcomes in Individuals With Type 2 Diabetes on GLP-1 RA Therapy
Pierpaolo Falcetta1, Rita Zilich2, Fabio Baccetti3
1Diabetes Unit, Azienda USL Toscana Centro, 50053 Empoli, Italy.
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.
Related Concept Videos
Glucagon-like Receptor Agonists
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
Oral Hypoglycemic Agents: Biguanides and Glitazones
Diabetes: Management and Pharmacotherapy
Insulin remains the cornerstone of treatment for most patients with type 1 and many...
Insulin: Dosing Regimen and Adverse Effects
The basal dose constitutes about 40%-50% of the total daily dose, with the rest as premeal insulin. The mealtime insulin dose should mirror...
Dipeptidyl Peptidase 4 Inhibitors
Diabetes Mellitus: Type 2 and Gestational

