The following is a summary of the “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,” published in the March 2023 issue of Diabetes and Endocrinology by Laffel, et al.

Young people are developing type 2 diabetes at an alarming rate, but few effective therapies exist to combat this epidemic. So they compared empagliflozin to placebo and linagliptin to a placebo to see which was more effective at lowering high blood sugar levels in young people with type 2 diabetes. Participants with type 2 diabetes (aged 10-17 years; HbA_1c 6.5-10% [48-91 mmol/mol]) who had previously been treated with metformin or insulin were randomly assigned (1:1:1) to receive either oral empagliflozin 10 mg, oral linagliptin 5 mg, or placebo in this double-blind, placebo-controlled trial conducted in 108 centers across 15 countries. Those in the empagliflozin group whose HbA_1c wasn’t below 7% (53 mmol/mol) by week 12 were randomized again (1:1) at week 14 to continue with 10 mg or increase to 25 mg. 

Patients in the placebo group were switched to either linagliptin 5 mg or one of the empagliflozin doses (10 mg or 25 mg) in a double-blind, random fashion at week 26 (1:1:1). At the time of the initial randomization and the re-randomizations at weeks 14 and 26 investigators received medication kits for all participants that had been pre-assigned to them in a blinded fashion through interactive response technology. The primary endpoint was the difference in HbA_1c levels between the beginning and end of the 26-week study period. All participants who took empagliflozin were included in a single statistical analysis. Evaluation of risk-free operation continued up to week 52; of the 262 individuals who were initially screened between April 26, 2018, and May 26, 2022, 158 (60%) were randomized to treatment (53 (34%) to placebo, 52 (33%) to empagliflozin 10 mg, and 53 (34%) to linagliptin). 

For the primary outcome, the adjusted mean HbA_1c change from baseline at week 26 was -0·84% [-9·2 mmol/mol] in the empagliflozin pooled group versus placebo (95% CI -1·50 to -0·19 [-16·4 to −2·1]; p=0·012); the corresponding change from baseline for linagliptin versus placebo was -0·34% [-3·8 mmol/mol; 95% CI -0·99 to 0·30 [-10·8 to 3·3]; p=0·29). Up to week 26, 34 people in the placebo group, 40 in the combined empagliflozin group, and 37 in the linagliptin group experienced adverse events. Two (4%) people in the placebo group, one (2%) person in the combined empagliflozin and linagliptin group, and one (2%) person in the linagliptin group reported severe adverse events. The most common adverse effect observed was hypoglycemia, which occurred more frequently in the active drug group than in the placebo group. Severe cases of hypoglycemia were not reported.

Compared to linagliptin, empagliflozin reduced HbA_1c by a clinically meaningful amount after considering the placebo effect, suggesting that it could be an effective treatment for young people with type 2 diabetes.

Source: sciencedirect.com/science/article/abs/pii/S2213858722003874