SUN-527 - Glucagon-Like Peptide-1 Receptor Agonists in Type 1 Diabetes: Lessons Learned from Medication Use and Agent Switching

Introduction:

The role of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in type 1 diabetes (T1DM) is not well established, and their use remains off-label. Patients with T1DM were excluded from major GLP-1RA cardiovascular and renal outcome trials, leaving a gap in safety and efficacy data. Of particular concern is the development of nausea and vomiting, common adverse effects of this medication class, and the increased risk of hyperglycemia with ketosis observed in trials with liraglutide. We present lessons learned from the case of a young adult with T1DM who presented with diabetic ketoacidosis (DKA) during a switch in his GLP-1RA therapy.

Case Description:

A 31-year-old man with T1DM presented with severe DKA. Initially diagnosed with type 2 diabetes in 2023 and treated with oral agents and basal insulin. In April 2024, after missing two days of insulin therapy, he presented with DKA. Workup revealed GAD-65 antibody positivity and a low C-peptide. At that time, his HbA1c was 12.4%, weight 57.6 kg, and BMI 17.7 kg/m². A diagnosis of T1DM was made and treatment was changed to basal-bolus insulin with continuous glucose monitoring. In November 2024, injectable semaglutide was added off-label and titrated to 1 mg weekly. He tolerated the semaglutide for almost a year with improved outpatient glycemic control (HbA1c 7.1% in July 2025). Following insurance formulary denial, semaglutide was discontinued and, after 2 weeks off therapy, he was started on dulaglutide 3 mg weekly. Soon after the first dulaglutide dose, he developed intractable vomiting with minimal oral intake. He omitted his basal insulin for 24 hours and presented in October 2025 with severe DKA. At this time, his weight was 72 kg, BMI 22.0 kg/m². Laboratory testing showed: HbA1c of 8.0%, glucose 584 mg/dL, anion gap >25, bicarbonate < 5 mEq/L, and β-hydroxybutyrate >9.0 mmol/L. After a 2-day ICU stay, he was discharged on an intensified basal-bolus regimen with reinforced sick-day education. Dulaglutide was discontinued. The patient noted he was not willing to reconsider future treatment with a GLP-1RA even at reduced doses.

Discussion:

This case highlights the utmost importance of education if initiating off-label treatment with GLP-1RAs in individuals with T1DM, and the need for extreme caution when escalating doses or switching to a new GLP-1RA. While stable on low-dose semaglutide, our patient lacked education on medication management during severe nausea/vomiting and the DKA risk associated with insulin omission. If using GLP-1RA in patients with T1DM, clinicians should err on the side of caution when initiating therapy or switching to a new agent, prescribing the lowest dose at initiation, aiming for low maintenance doses, and instructing the patient on needed insulin adjustments. Clinical trials assessing cardiorenal outcomes and safety of GLP-1RAs in T1DM are needed to support their use in practice.

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