Empagliflozin tied to meaningful reduction of HbA1c compared to linagliptin in young diabetes patients: Lancet

A new study published in The Lancet Diabetes & Endocrinology suggests that linagliptin did not reduce HbA1c in a clinically meaningful way, however empagliflozin did, suggesting a potential new therapy option for young patients with type 2 diabetes.

Type 2 diabetes is becoming more common among young people, yet there are few effective therapies. In order to evaluate the effectiveness and safety of an empagliflozin dosage regimen over placebo and linagliptin versus placebo on glycemic management in young persons with type 2 diabetes, Lori Laffel and colleagues conducted this study.

Participants with type 2 diabetes (aged 10–17; HbA1c 6–5–10% [48–91 mmol/mol]; previously treated with metformin or insulin) were randomized (1:1:1) to receive oral oral linagliptin 5 mg, empagliflozin 10 mg, or placebo in this double-blind, placebo-controlled trial conducted in 108 centers across 15 countries. During week 14, participants in the empagliflozin group received a second double-blinded randomization (1:1) to decide whether to continue taking 10 mg or increase to 25 mg if their HbA1c was not below 7 percent (53 mmol/mol) at that time. During week 26, participants in the placebo group were reassigned (1:1:1) to receive either linagliptin 5 mg or one of the empagliflozin dosages (10 mg or 25 mg). For the initial randomization and for the re-randomizations at weeks 14 and 26, all participants were randomly assigned to receive blinded medicine kits, and the investigators were kept anonymous throughout the experiment. Change from baseline in HbA1c at 26 weeks was the main result. Results for empagliflozin were based on a combined analysis of data from all subjects. Up until week 52, safety was evaluated.

The key findings of this study were:

1. 262 individuals were tested between April 26, 2018, and May 26, 2022; 158 (60%) were randomly allocated to therapy with empagliflozin 10 mg and 53 (34%), respectively.

2. The adjusted mean HbA1c change from baseline at week 26 for the main endpoint for the empagliflozin pooled group was -084%, whereas the change from baseline for linagliptin versus placebo was -034%. Until week 26, there were 34 (64%) people in the placebo group, 40 (77%) in the pooled group receiving empagliflozin, and 37 (71%) in the group receiving linagliptin who experienced adverse events.

3. Two (4%) people in the placebo group, one (2%) in the combined group using empagliflozin, and one (2%) in the group taking linagliptin reported having had serious side effects.

4. The most often reported adverse event was hypoglycemia, which occurred more frequently in patients receiving active medication than in those receiving a placebo.

5. There were no occurrences of severe hypoglycemia recorded.

Reference:

Laffel, L. M., Danne, T., Klingensmith, G. J., Tamborlane, W. V., Willi, S., Zeitler, P., Neubacher, D., Marquard, J., Bardymova, T., Barrientos Perez, M., Bethin, K., Bjornstad, P., Bondar, I., Chen, M., Choi, J.-H., Deerochanawong, C., … Yupanqui Lozno, H. (2023). Efficacy and safety of the SGLT2 inhibitor empagliflozin versus placebo and the DPP-4 inhibitor linagliptin versus placebo in young people with type 2 diabetes (DINAMO): a multicentre, randomised, double-blind, parallel group, phase 3 trial. In The Lancet Diabetes & Endocrinology (Vol. 11, Issue 3, pp. 169–181). Elsevier BV. https://doi.org/10.1016/s2213-8587(22)00387-4