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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

2023; Elsevier BV; Volume: 11; Issue: 3 Linguagem: Inglês

10.1016/s2213-8587(22)00387-4

2213-8595

Lori M. Laffel, Thomas Danne, Georgeanna J. Klingensmith, William V. Tamborlane, Steven M. Willi, Philip Zeitler, Dietmar Neubacher, Jan Marquard, Т. П. Бардымова, Margarita Barrientos Perez, Kathleen E. Bethin, Petter Bjornstad, Ирина Аркадьевна Бондарь, Mimi Chen, Jin‐Ho Choi, Mark A. Clements, Javier Ricardo Colomar, Mark Daniels, Chaicharn Deerochanawong, Vivek S Desai, Jean-Claude G Desmangles, Robert G Dillon, Naznin Dixit, Hongwei Du, Rachel Edelen, Diego Espinoza Peralta, María Verónica Felipe Gacioppo, Tânia Ferraz, Galina Galkina, Mary Patricia Gallagher, Minu George, Edgar R. Gonzalez, Michael Gottschalk, Giancarlo Guido, Amir Ali Hassan, Eli Hershkovitz, Lina Huerta‐Saenz, Jin Soon Hwang, Jaime Orlando Ibarra Gomez, Lydia Irizarry Gonzalez, Nina Jain, David H. Jelley, Ho-Seong Kim, T. A. Kovalenko, Lori M. Laffel, Steven B. Leichter, Raphael Del Roio Liberatore, Jane Lynch, Farid H. Mahmud, Oleg Arturovich Malievskiy, Andrew Muir, Bryce Nelson, Luis Alejandro Nevarez Ruiz, Micah L. Olson, Emilia Susana Pelayo Orozco, Valentina Peterkova, Fernando Ramón Ramírez Mendoza, Konda Mohan Reddy, Henry Rodriguez, Javier Andres Saenz, Julia Samoilova, Karl‐Otfried Schwab, S. Shah, Naim Shehadeh, Ashley H. Shoemaker, Yulia Skorodok, Aleksandr Sobolev, Silvana Ernestina Solís, Shylaja Srinivasan, William V. Tamborlane, Eva Tsalikian, Ф. В. Валеева, Carl D Vance, Pedro Velasquez‐Mieyer, R. Ortiz, Olga Votyakova, Haiyan Wei, Ruth S. Weinstock, Mark D. Wheeler, Brandy Wicklow, Steven M. Willi, Kupper A. Wintergerst, Risa M. Wolf, Jamie Wood, Chandan Yaliwal, Hernán Yupanqui Lozno,

Diabetes Management and Research

Summary Background The incidence of type 2 diabetes in young people is increasing, but treatments remain limited. We aimed to assess the efficacy and safety of an empagliflozin dosing regimen versus placebo and linagliptin versus placebo on glycaemic control in young people with type 2 diabetes. Methods In this double-blind, placebo-controlled trial done in 108 centres in 15 countries, participants with type 2 diabetes (aged 10–17 years; HbA 1c 6·5–10·5% [48–91 mmol/mol]) who had been previously treated with metformin or insulin were randomly assigned (1:1:1) to oral empagliflozin 10 mg, oral linagliptin 5 mg, or placebo. Participants in the empagliflozin group who did not have HbA 1c below 7·0% (<53 mmol/mol) by week 12 underwent a second double-blinded randomisation (1:1) at week 14, either remaining on 10 mg or increasing to 25 mg. Participants in the placebo group were randomly reassigned (1:1:1) in a double-blinded manner at week 26 to linagliptin 5 mg or one of the empagliflozin doses (10 mg or 25 mg). Investigators were masked throughout the trial and received assignments of blinded medication kits through interactive response technology for all participants at the initial randomisation and for the re-randomisations at weeks 14 and 26. The primary outcome was change from baseline in HbA 1c at 26 weeks. For empagliflozin, results were based on a pooled analysis for all participants on empagliflozin. Safety was assessed until week 52. This trial is registered with ClinicalTrials.gov, NCT03429543. Findings Between April 26, 2018, and May 26, 2022, of 262 screened participants, 158 (60%) were randomly assigned 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). Adverse events occurred in 34 (64%) participants in the placebo group, 40 (77%) in the empagliflozin pooled group, and 37 (71%) in the linagliptin group, up to week 26. Of these, severe adverse events were reported in two (4%) participants in the placebo group, one (2%) in the empagliflozin pooled group, and one (2%) in the linagliptin group. Hypoglycaemia was the most frequently reported adverse event with higher rates for those on active drug treatment compared with placebo. No severe hypoglycaemia cases were reported. Interpretation Empagliflozin provided clinically relevant placebo-corrected reductions in HbA 1c , whereas linagliptin did not, and might offer a new treatment option for young people with type 2 diabetes. Funding The Boehringer Ingelheim and Eli Lilly and Company Alliance.