Real world study on the Clinical and Safety Outcomes With GLP-1 Receptor Agonists and SGLT2 Inhibitors in Type 1 Diabetes

Abstract

The metabolic benefits of GLP-1 Receptor Agonists and SGLT2 Inhibitors in patients with type 2 diabetes are now well recognised. However, ongoing uncertainties persists regarding their use in people with type 1 diabetes mainly due to safety concerns and lack of evidence from large scale randomised clinical trials. Despite this, Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) are often used off-label in the management of type 1 diabetes mellitus (T1DM) in real-world practice as adjuvant therapies to insulin to improve metabolic outcomes. A recent study published in the Journal of Clinical Endocrinology and Metabolism was therefore aimed to determine the efficacy and safety of GLP-1RAs and sodium-glucose SGLT2is in the management of T1DM in real-world practice. Using a retrospective chart review, the investigators identified 104 patients with T1DM who ever used a GLP-1RA (76 patients) or SGLT2i (39 patients) for more than 90 days. They reported that after 1 year of therapy, GLP-1RA users had statistically significant reductions in weight (90.5 kg to 85.4 kg; P < .001), HbA_1c (7.7% to 7.3%; P = .007), and total daily dose of insulin (61.8 units to 41.9 units; P < .001). SGLT2i users also experienced significant reductions in HbA_1c (7.9% to 7.3%; P < .001) and basal insulin (31.3 units to 25.6 units; P = .003). GLP-1RA users compared to SGLT2i users had greater reduction in weight while HbA_1c reduction was comparable between the groups. Importantly, over a mean total duration of use of 29.5 months/patient for both groups, more SGLT2i users experienced diabetic ketoacidosis (DKA) (12.8% vs 3.9%). Discontinuation rate between the two therapies were comparable (26.9% of the time for GLP-1RA users vs 27.7% for SGLT2i users). Overall, this real world study provided evidence of metabolic benefits in patients with type 1 diabetes. However, DKA remains a clinical concern with SGLT2i use, requiring careful patient selection and monitoring, with the risk to benefit ratio of treatment evaluated at an individual level.