Daily GLP-1 Receptor Agonists Showed Glycemic Efficacy in T1D but Faced Hypoglycemia and Ketosis Safety Issues

Type 1 diabetes (T1D) is an autoimmune condition requiring lifelong insulin therapy, yet achieving optimal glycemic control without increasing hypoglycemia risk remains challenging. Current insulin regimens often struggle to manage postprandial glucose excursions and associated weight gain, leaving a gap for adjunctive therapies. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are well-established for Type 2 diabetes and obesity due to their glucose-dependent insulinotropic effects, glucagon suppression, and gastric emptying delay, making them a logical candidate for T1D adjunct therapy.

This review synthesized findings from past Phase 2 and Phase 3 clinical trials investigating daily injectable GLP-1 receptor agonists as adjunct therapy for Type 1 diabetes. It examined efficacy on glycemic control and weight, alongside reported safety profiles, particularly concerning hypoglycemia and ketosis. The analysis considered the historical context of these trials, noting the absence of widespread continuous glucose monitoring (CGM) and the use of "one size fits all" insulin titration rules, which may have influenced outcomes.

Phase 2 clinical trials demonstrated promising signals for efficacy of daily GLP-1RAs on glycemic control and weight reduction in Type 1 diabetes. These beneficial effects were subsequently confirmed in larger Phase 3 trials. > However, these larger trials were accompanied by significant safety issues, including increased rates of hypoglycemia and ketosis. Notably, these trials were conducted before the widespread availability of continuous glucose monitoring (CGM) and utilized simple, standardized "one size fits all" rules for insulin dose titration, which likely contributed to the observed adverse events. The findings highlight the critical need for more individualized insulin management strategies when GLP-1RAs are used in T1D.