Effects of non-insulin anti-hyperglycemic agents in persons with type 1 diabetes

Introduction: The only agents approved by the FDA for use in people with Type 1 diabetes mellitus (T1DM) include insulin and pramlintide. The beta-cell centric classification of diabetes provides rationale for using non-insulin agents to target other organ systems to improve glucose management. This study aims to evaluate the efficacy and safety of metformin, sodium-glucose co-transporter 2 (SGLT2) inhibitors, and glucagon-like peptide 1 (GLP-1) receptor agonists for adults with T1DM. Research Question or Hypothesis: Is the use of metformin, SGLT2 inhibitors, or GLP-1 receptor agonists added to insulin safe and effective in adults with T1DM? Study Design: Retrospective, pre-post comparison Methods: Participants with a diagnosis of T1DM, who were initiated on metformin, SGLT2 inhibitors, or GLP-1 receptor between January 2013 and December 2017 were included. People with type 2 diabetes diagnosis, pregnancy, C-peptide level > 0.5 ng/mL, or absence of documented HbA1c at baseline or post initiation were excluded. The primary efficacy endpoint was change in hemoglobin A1c (HbA1c) from baseline to 6 months, while the secondary efficacy endpoint was change in bodyweight from baseline to 6 months. Data was analyzed using Wilcoxon sign-ranked. Results: A total of 171 participants were included. During the study period, the three-month HbA1c decreased from 8.4% (IQR 7.7 - 9.5) to 8.05% (IQR 7.2 - 8.9) (P = 0.002). The six-month HbA1c decreased from 8.4% (IQR 7.6 - 9.3) to 8.1% (IQR 7.3 - 9) (P = 0.006). The sixmonth weight comparison decreased from 92.5 kg (IQR 79.5 - 104.8) to 90.0 kg (IQR 75.8 - 103) (P < 0.0001). There was more weight loss with GLP-1 receptor agonists, with a weight lowering of 6 kg from baseline. Conclusion: In this real world study, both weight and HbA1c decreased at three and six months after initiation of non-insulin agents in people with T1DM. The study was not large enough to detect differences between classes.