TY - JOUR
T1 - Cardiovascular safety and lower severe hypoglycaemia of insulin degludec versus insulin glargine U100 in patients with type 2 diabetes aged 65 years or older
T2 - Results from DEVOTE (DEVOTE 7)
AU - On Behalf Of The Devote Study Group
AU - Pratley, Richard E.
AU - Emerson, Scott S.
AU - Franek, Edward
AU - Gilbert, Matthew P.
AU - Marso, Steven P.
AU - McGuire, Darren K.
AU - Pieber, Thomas R.
AU - Zinman, Bernard
AU - Hansen, Charlotte T.
AU - Hansen, Melissa V.
AU - Mark, Thomas
AU - Moses, Alan C.
AU - Buse, John B.
N1 - Funding Information:
S. P. M. has received personal fees from Abbott Vascular, Novo Nordisk, University of Oxford and Bristol-Myers Squibb; and has received research support from Novo Nordisk, the Medicines Company and Terumo Medical.
Funding Information:
R. E. P. has received consultancy and speaker fees from AstraZeneca, Takeda and Novo Nordisk; has received consultancy fees from Boehringer Ingelheim, GlaxoSmithKline, Hanmi Pharmaceutical Co. Ltd., Janssen Scientific Affairs LLC, Ligand Pharmaceuticals, Inc., Eli Lilly, Merck, Pfizer and Eisai, Inc.; and has received research grants from Gilead Sciences, Lexicon Pharmaceuticals, Ligand Pharmaceuticals, Inc., Eli Lilly, Merck, Sanofi US LLC and Takeda, all of which were paid directly to Florida Hospital, a non-profit organization.
Funding Information:
S. S. E. has received personal fees related to Data Monitoring Committees from CTI BioPharma, Arena Pharmaceuticals, SFJ Pharmaceuticals, BioMarin, Medivation, Biom'up, Bristol-Myers Squibb, Dynavax, Genentech, GlaxoSmithKline, Janssen Research, Novartis, Pfizer, Roche, Sarepta Therapeutics and Xoma; has received personal fees related to other statistical consulting from Amgen, AstraZeneca, Celltrion, Daiichi Sankyo, Nektar Pharmaceuticals, Novo Nordisk, Sage Therapeutics, Shire, Sprout Pharmaceuticals, Sanofi, Takeda Pharmaceutical Company, Collegium Pharmaceutical, Intercept, Coherus BioMedical and Emmaus Life Sciences; and has received research grant support from the National Heart, Lung, and Blood Institute (NHLBI).
Funding Information:
B. Z. has received grant support from Boehringer Ingelheim, AstraZeneca and Novo Nordisk; and has received consulting fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk and Sanofi.
Funding Information:
T. R. P. has received research support from Novo Nordisk and AstraZeneca, paid directly to the Medical University of Graz; has received personal fees for consulting from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Novo Nordisk and Roche Diabetes Care; and is the Chief Scientific Officer of CBmed (Center for Biomarker Research in Medicine), a public-funded biomarker research company.
Funding Information:
DEVOTE research activities were supported at numerous US centres by Clinical and Translational Science Awards from the National Institutes of Health's National Center for Advancing Translational Science.
Funding Information:
J. B. B. has received contracted consulting fees, paid to the University of North Carolina, from Adocia, AstraZeneca, Eli Lilly, MannKind, NovaTarg, Novo Nordisk, Senseonics, and vTv Therapeutics; has received grant support from Novo Nordisk, Sanofi and vTv Therapeutics; is a consultant to Neurimmune AG; is supported by a grant from the National Institutes of Health (UL1TR002489); and holds stock options in Mellitus Health, PhaseBio and Stability Health.
Publisher Copyright:
© 2019 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.
PY - 2019/7
Y1 - 2019/7
N2 - Aims: The aim of this study was to describe the risks of cardiovascular (CV) events and severe hypoglycaemia with insulin degludec (degludec) vs insulin glargine 100 units/mL (glargine U100) in patients with type 2 diabetes (T2D) aged 65 years or older. Materials and methods: A total of 7637 patients in the DEVOTE trial, a treat-to-target, randomized, double-blind trial evaluating the CV safety of degludec vs glargine U100, were divided into three age groups (50-64 years, n = 3682; 65-74 years, n = 3136; ≥75 years, n = 819). Outcomes by overall age group and randomized treatment differences were analysed for major adverse cardiovascular events (MACE), all-cause mortality, severe hypoglycaemia and serious adverse events (SAEs). Results: Patients with increasing age had higher risks of CV death, all-cause mortality and SAEs, and there were non-significant trends towards higher risks of MACE and severe hypoglycaemia. Treatment effects on the risk of MACE, all-cause mortality, severe hypoglycaemia and SAEs were consistent across age groups, based on the non-significant interactions between treatment and age with regard to these outcomes. Conclusions: There were higher risks of CV death, all-cause mortality and SAEs, and trends towards higher risks of MACE and severe hypoglycaemia with increasing age after adjusting for baseline differences. The effects across age groups of degludec vs glargine U100 on MACE, all-cause mortality and severe hypoglycaemia were comparable, suggesting that the risk of MACE, as well as all-cause mortality, is similar and the risk of severe hypoglycaemia is lower with degludec regardless of age. Evidence is conclusive only until 74 years of age.
AB - Aims: The aim of this study was to describe the risks of cardiovascular (CV) events and severe hypoglycaemia with insulin degludec (degludec) vs insulin glargine 100 units/mL (glargine U100) in patients with type 2 diabetes (T2D) aged 65 years or older. Materials and methods: A total of 7637 patients in the DEVOTE trial, a treat-to-target, randomized, double-blind trial evaluating the CV safety of degludec vs glargine U100, were divided into three age groups (50-64 years, n = 3682; 65-74 years, n = 3136; ≥75 years, n = 819). Outcomes by overall age group and randomized treatment differences were analysed for major adverse cardiovascular events (MACE), all-cause mortality, severe hypoglycaemia and serious adverse events (SAEs). Results: Patients with increasing age had higher risks of CV death, all-cause mortality and SAEs, and there were non-significant trends towards higher risks of MACE and severe hypoglycaemia. Treatment effects on the risk of MACE, all-cause mortality, severe hypoglycaemia and SAEs were consistent across age groups, based on the non-significant interactions between treatment and age with regard to these outcomes. Conclusions: There were higher risks of CV death, all-cause mortality and SAEs, and trends towards higher risks of MACE and severe hypoglycaemia with increasing age after adjusting for baseline differences. The effects across age groups of degludec vs glargine U100 on MACE, all-cause mortality and severe hypoglycaemia were comparable, suggesting that the risk of MACE, as well as all-cause mortality, is similar and the risk of severe hypoglycaemia is lower with degludec regardless of age. Evidence is conclusive only until 74 years of age.
KW - basal insulin
KW - cardiovascular disease
KW - hypoglycaemia
KW - type 2 diabetes
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U2 - 10.1111/dom.13699
DO - 10.1111/dom.13699
M3 - Article
C2 - 30850995
AN - SCOPUS:85064525797
VL - 21
SP - 1625
EP - 1633
JO - Diabetes, Obesity and Metabolism
JF - Diabetes, Obesity and Metabolism
SN - 1462-8902
IS - 7
ER -