P4A043: Durable Improvement in Glycated Hemoglobin in Youth-onset Type 2 Diabetes: A Post Hoc Analysis of the DINAMO Trial of Empagliflozin and Linagliptin versus Placebo

Background: The increasing prevalence of childhood overweight and obesity has led to a substantial increase in type 2 diabetes (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. There is a dearth of treatments for youth-onset T2D, with metformin the only globally approved oral agent, and all other treatment options requiring injection. Thus, there is an unmet need for additional oral therapies. The DINAMO trial (NCT03429543) compared the efficacy and safety of two oral antidiabetic agents, the sodium-glucose co-transporter-2 (SGLT2) inhibitor empagliflozin, and the dipeptidyl peptidase-4 inhibitor linagliptin, with placebo in 157 participants aged 10–17 years. The aim of this post hoc analysis of the DINAMO trial was to analyze glycemic control in the participants at 26 and 52 weeks.

Methods: 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 glycated hemoglobin (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.

Results: Significantly more participants responded to empagliflozin versus 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 versus placebo were not significant. Empagliflozin provided a clinically meaningful response even at higher HbA1c and fasting plasma glucose levels (Table).

Conclusion: 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.