Durable Improvement in HbA1c in Youth-Onset T2D-A Post Hoc Analysis of the DINAMO Trial of Empagliflozin and Linagliptin vs. Placebo

The increasing prevalence of childhood overweight and obesity has led to a substantial increase in T2D in youth. The clinical course of youth-onset T2D is more aggressive than in adults, with a faster decline in beta‑cell function leading to worse glycemic control and an early onset of complications. The DINAMO trial compared the efficacy and safety of empagliflozin and linagliptin with placebo in 157 participants aged 10-17 years. Participants were randomized (1:1:1) to linagliptin 5 mg, empagliflozin 10 mg, or placebo. At Week 12, those in the empagliflozin group who did not attain HbA1c <7.0% were re‑randomized (1:1) to empagliflozin 10 or 25 mg. Responders were defined as having no rescue medication and a HbA1c change from baseline ≤-0.5% or attained HbA1c <7.0% at Week 26. Empagliflozin results were pooled. Significantly more participants responded to empagliflozin vs placebo (rate difference 23.6, 95% CI 4.3-41.4; p=0.01); this response was maintained to Week 52 by 40% of the group. Results for linagliptin vs placebo were not significant. Empagliflozin provided a clinically meaningful response even at higher HbA1c and FPG levels (Table). These results show that empagliflozin provides a clinically relevant, statistically significant, and durable improvement in glycemic control, suggesting SGLT2 inhibitors could be a new therapy for T2D in youth. Disclosure L. M. Laffel: Advisory Panel; Medtronic, Lilly Diabetes, Novo Nordisk, Vertex Pharmaceuticals Incorporated, Roche Diagnostics, Provention Bio, Inc., Consultant; Dexcom, Inc., Janssen Pharmaceuticals, Inc., Medscape. T. Danne: Research Support; Abbott Diabetes, AstraZeneca, Bayer Inc., Boehringer-Ingelheim, Dexcom, Inc., Eli Lilly and Company, Novo Nordisk A/S, Sanofi, Medtronic, Stock/Shareholder; DreaMed Diabetes, Ltd. W. V. Tamborlane: None. G. J. Klingensmith: Advisory Panel; Boehringer Ingelheim Inc., Consultant; AstraZeneca, Boehringer Ingelheim Inc., Novo Nordisk, Takeda Pharmaceutical Co., Ltd. D. Neubacher: Employee; Boehringer Ingelheim Pharma GmbH&Co. KG. I. Tartakovsky: Employee; Boehringer Ingelheim International GmbH. J. Marquard: Employee; Boehringer Ingelheim Inc. P. Zeitler: Consultant; Eli Lilly and Company, Boehringer Ingelheim Inc., Johnson & Johnson. S. M. Willi: Advisory Panel; Boehringer Ingelheim International GmbH, Medtronic. Funding Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance