Clinical and Safety Outcomes With GLP-1 Receptor Agonists and SGLT2 Inhibitors in Type 1 Diabetes: A Real-World Study

Abstract

Context: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) are used off-label in the management of type 1 diabetes mellitus (T1DM) in real-world practice as adjuvant therapies to insulin. There are few real-world data regarding efficacy and safety of this practice.

Objective: This work aimed to determine the efficacy and safety of GLP-1RAs and sodium-glucose SGLT2is in the management of T1DM in real-world practice.

Methods: A retrospective chart review was performed of all instances of GLP-1RA and/or SGLT2i use greater than 90 days in adult patients with T1DM at a single academic center. We report the clinical and safety outcomes over the duration of use.

Results: We identified 104 patients with T1DM who ever used a GLP-1RA (76 patients) or SGLT2i (39 patients) for more than 90 days. After 1 year of therapy, GLP-1RA users had statistically significant reductions in weight (90.5 kg to 85.4 kg; P < .001), glycated hemoglobin A1c (HbA1c) (7.7% to 7.3%; P = .007), and total daily dose of insulin (61.8 units to 41.9 units; P < .001). SGLT2i users had statistically significant reductions in HbA1c (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 (P = .027) while HbA1c reduction was comparable between the groups. 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%). Therapy was discontinued because of adverse events 26.9% of the time for GLP-1RA users vs 27.7% for SGLT2i users.

Conclusion: GLP-1RA and SGLT2i use in T1DM is associated with clinically relevant benefits. 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.

Keywords: GLP-1RA; SGLT2i; real-world outcomes; safety; t1DM.