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Diabetes and Vascular Disease

SUN-518 - Outcomes in Adults with Type 1 Diabetes Treated with Triple Therapy: Insulin, Sodium-Glucose Cotransporter-2 Inhibitors, and Glucagon-Like Peptide-1 ± Glucose-Dependent Insulinotropic Polypeptide Receptor Agonists

Sunday, June 14, 2026
9:00 AM - 4:00 PM CT
Location: ENDOExpo; Poster Floor
Disclosure(s):
Tasma Harindhanavudhi, MD: No financial relationships to disclose
Background
Adjunctive non-insulin therapies, including sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 ± glucose-dependent insulinotropic polypeptide (GLP-1 ± GIP) receptor agonists, are increasingly used in type 1 diabetes (T1D). However, real-world outcomes data in adults with T1D treated with triple therapy (insulin, SGLT2i, and GLP-1 ± GIP receptor agonists) is limited. We aimed to evaluate glycemic and metabolic outcomes in adults with T1D treated with triple therapy.
Methods
We identified adults with T1D treated between 1/1/2017 and 3/20/2025 at an academic health system in the Upper Midwest, United States, by adapting the SUPREME-DM and Klompas algorithms to our electronic health record. Among these individuals, we identified those treated concurrently with triple therapy. Co-primary outcomes were differences in HbA1c and BMI between treatment periods (i.e., insulin monotherapy vs. dual therapy [insulin + SGLT2i or insulin + GLP-1 ± GIP] vs. triple therapy). HbA1c and BMI were compared across treatment periods using linear mixed-effects models.
Results
We analyzed a cohort of 25 adults (mean age 55.3 ± 14.2 years; 44% female). At baseline, 36% had chronic kidney disease, 12% had heart failure, 24% had cardiovascular disease, 36% had obstructive sleep apnea, and 76% had BMI ≥ 30 kg/m2. Dual therapy consisted of insulin + SGLT2i in 17 patients (68%) and insulin + GLP-1 ± GIP in 8 patients (32%). Compared to insulin monotherapy (HbA1c 8.4 ± 1.1%), HbA1c was significantly lower with insulin + SGLT2i (7.9 ± 1.0%, p< 0.001), insulin + GLP-1 ± GIP (7.6 ± 0.8%, p< 0.001), and triple therapy (8.1 ± 1.2%, p=0.004).
Compared to insulin monotherapy (mean BMI 35.0 ± 5.9 kg/m²), the mean BMI was significantly lower with insulin + SGLT2i (33.5 ± 7.3 kg/m², p=0.010) and triple therapy (31.2 ± 7.8 kg/m², p=0.001), but not insulin + GLP-1 ± GIP (30.4 ± 5.6 kg/m², p=0.063).
Triple therapy achieved significantly lower BMI compared to insulin + SGLT2i (p=0.043) but not insulin + GLP-1 ± GIP (p=0.977). There were no DKA-related hospitalizations during dual or triple therapy. Two patients had a hypoglycemia-related emergency department visit or hospitalization during triple therapy.
Discussion
In this real-world cohort of adults with T1D, triple therapy with insulin, SGLT2i, and GLP-1 ± GIP significantly reduced HbA1c and BMI compared to insulin monotherapy. While limited by the small cohort and retrospective design, these findings support the need for a randomized controlled trial to establish the efficacy and safety of triple therapy in adults with T1D.

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