The importance of addressing multiple risk markers in type 2 diabetes: Results from the LEADER and SUSTAIN 6 trials

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  • Emilie H. Zobel
  • Bernt Johan von Scholten
  • Tine W. Hansen
  • Frederik Persson
  • Søren Rasmussen
  • Benjamin Wolthers
  • Rossing, Peter

Aims: To investigate to what extent multiple risk marker improvements confer lower risk of cardiovascular and kidney complications in a contemporary type 2 diabetes population. Materials and methods: Post-hoc analysis of the LEADER (n = 8638; median follow-up 3.8 years) and SUSTAIN 6 (n = 3040; median follow-up 2.1 years) cardiovascular outcome trials. Participants were those with baseline and year-1 assessment of at least one of the parameters of interest; we pooled the liraglutide-/semaglutide- and placebo-treated groups and categorized them by number of risk markers with clinically relevant improvements after 1 year of study participation. We investigated risk of major adverse cardiovascular events (MACE), expanded MACE, cardiovascular death and nephropathy. Predefined clinically relevant changes: body weight loss ≥5%; reductions in: glycated haemoglobin ≥1%, systolic blood pressure ≥5 mmHg and low-density lipoprotein cholesterol ≥0.5 mmol/L; estimated glomerular filtration rate change ≥0 ml/min/1.73 m2 and urinary albumin-to-creatinine ratio change ≥30% of baseline value. Cox regression analysed risk of outcomes adjusted for baseline risk marker levels and treatment group and stratified by trial. Results: Participants with two, three, or four or more improved risk markers versus participants with no risk marker improvement had reduced risk of expanded MACE [hazard ratio (95% confidence interval) 0.80 (0.67-0.96); 0.80 (0.66-0.97); 0.82 (0.66-1.02)], cardiovascular death [0.66 (0.45-0.96), 0.67 (0.45-0.99), 0.60 (0.38-0.94)] and nephropathy [0.71 (0.52-0.97), 0.48 (0.34-0.68), 0.43 (0.29-0.65)]. Conclusions: In persons with type 2 diabetes, improvements in ≥2 risk markers conferred cardiovascular risk reduction versus none or one improved risk marker. The nephropathy risk decreased with improvement in more risk markers. These findings stress the importance of multifactorial interventions targeting all risk markers.

Original languageEnglish
JournalDiabetes, Obesity and Metabolism
Volume24
Issue number2
Pages (from-to)281-288
Number of pages8
ISSN1462-8902
DOIs
Publication statusPublished - Feb 2022

Bibliographical note

Funding Information:
Data contained within this manuscript was accepted as an abstract at the European Renal Association - European Dialysis and Transplant Association congress, 5-8 June 2021. Medical writing support was provided by Brendan Deeney, BSc, and editorial assistance provided by Izabel James, MBBS, both of Ashfield MedComms, an Ashfield Health company, funded by Novo Nordisk A/S. Role of the sponsor: this study was supported by Novo Nordisk, which also had a role in the design, analysis and reporting of the trials.

Funding Information:
Data contained within this manuscript was accepted as an abstract at the European Renal Association ‐ European Dialysis and Transplant Association congress, 5‐8 June 2021. Medical writing support was provided by Brendan Deeney, BSc, and editorial assistance provided by Izabel James, MBBS, both of Ashfield MedComms, an Ashfield Health company, funded by Novo Nordisk A/S. Role of the sponsor: this study was supported by Novo Nordisk, which also had a role in the design, analysis and reporting of the trials.

Funding Information:
EHZ is now a Novo Nordisk A/S full‐time employee, but work related to this article was carried out when EHZ was employed full‐time by Steno Diabetes Center Copenhagen. BW, BJvS and SR are Novo Nordisk A/S full‐time employees and BW, BJvS, SR and TWH are Novo Nordisk shareholders. FP reports research grants from AstraZeneca and lecture fees from AstraZeneca, MSD, Janssen, Eli Lilly, Boehringer Ingelheim, Novo Nordisk A/S and Novartis, as well as being a consultant/advisory board member for AstraZeneca, Bayer, Amgen and MSD. PR has received honoraria from Steno Diabetes Center Copenhagen for advisory work, and for consultancy/education from Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, MSD, Merck, Mundipharma, Novo Nordisk, Vifor and Sanofi.

Publisher Copyright:
© 2021 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

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