SGLTi treatment improves glycemic control and reduces insulin dosing but increases the risk of diabetic ketoacidosis (DKA). Combination therapy (SGLTi + GRA) could augment glycemic and insulin dosing benefits while mitigating DKA risk.
Subjects with T1D (n=12) received 4-week insulin-adjunctive treatments with (a) SGLTi (dapagliflozin 10 mg) + placebo and (b) SGLTi + GRA (volagidemab 70 mg) in a cross-over, double-blind design. At baseline and end of each treatment, CGM and insulin dosing were recorded, and subjects completed an 8-hr insulin withdrawal test (IWT).
Average glucose improved with both SGLTi (138 mg/dL; P < 0.01) and SGLTi + GRA (131 mg/dL; P < 0.01) compared to Baseline (150 mg/dL). Total daily insulin dose was reduced with SGLTi (0.52 U/kg/day) compared to Baseline (0.56 U/kg/day; P = 0.06) and was reduced further with SGLTi + GRA treatment (0.41 U/kg/day; P < 0.01 vs SGLTi). Peak beta-hydroxybutyrate (BHB) concentrations during IWT were lower with SGLTi + GRA treatment (2.03 mmol/L) than with SGLTi alone (2.44 mmol/L; P = 0.04); there was no significant difference in peak BHB with either treatment vs Baseline (2.14 mmol/L).
Treatment with SGLTi + GRA improved glycemic control, reduced insulin use, and mitigated ketosis during hypoinsulinemia. These data suggest that combination adjunctive therapy may be effective to address multiple metabolic abnormalities in T1D.
S.C.Boeder: Consultant; Cecelia Health, Research Support; Dexcom, Inc., REMD Biotherapeutics, Eli Lilly and Company. M.J.Le roux: None. E.R.Giovannetti: None. A.Armstrong: None. L.Carter: None. R.L.Thomas: None. J.M.Gregory: Advisory Panel; Eli Lilly and Company, vTv Therapeutics, Other Relationship; Medtronic. J.Pettus: Advisory Panel; Sanofi, Novo Nordisk, Lilly, MannKind Corporation, Consultant; Carmot Therapeutics, Inc., Diasome.
National Institutes of Health (P30DK063491, UL1TR001442); Diabetes Research Connection
