@article{3d70544e29ef4b3c8930a1a870ecd0e7,
title = "Cardiovascular outcomes and safety with linagliptin, a dipeptidyl peptidase-4 inhibitor, compared with the sulphonylurea glimepiride in older people with type 2 diabetes: A subgroup analysis of the randomized CAROLINA trial",
abstract = "Aim: To compare the cardiovascular (CV) safety of linagliptin with glimepiride in older and younger participants in the CAROLINA trial in both prespecified and post hoc analyses. Materials and Methods: People aged 40 to 85 years with relatively early type 2 diabetes, inadequate glycaemic control and elevated CV risk were randomly assigned to linagliptin 5 mg or glimepiride 1 to 4 mg. The primary endpoint was time to first occurrence of three-point major adverse CV events (MACE: CV death, non-fatal myocardial infarction, or non-fatal stroke). We evaluated clinical and safety outcomes across age groups. Results: Of 6033 participants, 50.7% were aged <65 years, 35.3% were aged 65 to 74 years, and 14.0% were aged ≥75 years. During the 6.3-year median follow-up, CV/mortality outcomes did not differ between linagliptin and glimepiride overall (hazard ratio [HR] for three-point MACE 0.98, 95.47% confidence interval [CI] 0.84, 1.14) or across age groups (interaction P >0.05). Between treatment groups, reductions in glycated haemoglobin were comparable across age groups but moderate-to-severe hypoglycaemia was markedly reduced with linagliptin (HR 0.18, 95% CI 0.15, 0.21) with no differences among age groups (P = 0.23). Mean weight was −1.54 kg (95% CI –1.80, –1.28) lower for linagliptin versus glimepiride. Adverse events increased with age, but were generally balanced between treatment groups. Significantly fewer falls or fractures occurred with linagliptin. Conclusions: Linagliptin and glimepiride were comparable for CV/mortality outcomes across age groups. Linagliptin had significantly lower risk of hypoglycaemia and falls or fractures than glimepiride, including in “older-old” individuals for whom these are particularly important treatment considerations.",
keywords = "DPP-4 inhibitor, cardiovascular disease, clinical trial, hypoglycaemia, linagliptin, sulphonylureas",
author = "Espeland, {Mark A.} and Pratley, {Richard E.} and Julio Rosenstock and Takashi Kadowaki and Yutaka Seino and Bernard Zinman and Nikolaus Marx and McGuire, {Darren K.} and Andersen, {Knut Robert} and Michaela Mattheus and Annett Keller and Maria Weber and Johansen, {Odd Erik}",
note = "Funding Information: M.A.E. reports receiving consulting fees from Boehringer Ingelheim during the conduct of the study, and Ironwood Pharmaceuticals, and grants from the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute on Aging outside the submitted work. R.E.P. has received research funding from Lexicon Pharmaceuticals, Lilly, Merck, Novo Nordisk, Sanofi Aventis US, LLC and Takeda, speaker fees from AstraZeneca, Boehringer Ingelheim, Novo Nordisk and Takeda, and consultancy fees from AstraZeneca, Boehringer Ingelheim, Janssen Scientific Affairs, LLC, Ligand Pharmaceuticals, Inc, Lilly, Merck, Novo Nordisk, Sanofi Aventis US, LLC and Takeda. All honoraria and fees are directed to a non‐profit organization; he received no direct compensation. J.R. has served on scientific advisory boards and received honoraria or consulting fees from Applied Therapeutics, Eli Lilly, Sanofi, Novo Nordisk, Janssen, Oramed, Boehringer Ingelheim and Intarcia, and has also received grants/research support from Applied Therapeutics, Merck, Pfizer, Sanofi, Novo Nordisk, Oramed, Eli Lilly, GlaxoSmithKline, Genentech, Janssen, Lexicon, Boehringer Ingelheim and Intarcia. T.K. reports consulting/lecture fees from Abbott, Asahi Mutual Life Insurance, Astellas Pharma Inc., AstraZeneca K.K., Bayer, Boehringer Ingelheim, Cosmic, Daiichi Sankyo Company, Limited, Eli Lilly and Company, Fujifilm, FUJIREBIO, Johnson & Johnson Co., Ltd., Kissei Pharmaceutical Co., Ltd., Kowa Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Medical Review, Medscape Education, Medtronic Sofamor Danek, Mitsubishi Tanabe Pharma Corporation, MSD, Musashino Foods, Nipro, Novartis International AG, Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi S.A., SANWA KAGAKU KENKYUSHO CO., LTD., Sumitomo Dainippon, Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited and Terumo, grants from Astellas Pharma Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Kissei Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, MSD, Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi S.A., Sumitomo Dainippon, Taisho Pharmaceutical Co., Ltd. and Takeda Pharmaceutical Company Limited, contracted research from AstraZeneca K.K. and Takeda Pharmaceutical Company Limited, joint research from Daiichi Sankyo Company, Limited, and endowed chair fromAsahi Mutual Life Insurance, Boehringer Ingelheim, Kowa Co., Ltd., Mitsubishi Tanabe Pharma Corporation, MSD, Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd and Takeda Pharmaceutical Company Limited. Y.S. has received consulting/lecture fees from MSD K.K., Kao, Taisho, Boehringer Ingelheim, Eli Lilly, Becton Dickinson, Takeda and Novo Nordisk, and research support from Terumo, Boehringer Ingelheim, Ono, Arkray Marketing, Sumitomo Dainippon, Taisho and Novo Nordisk. B.Z. has received research grants awarded to his institution from Boehringer Ingelheim, AstraZeneca and Novo Nordisk, and honoraria from Janssen, Sanofi, Eli Lilly and Company, Boehringer Ingelheim, Novo Nordisk and Merck Sharp & Dohme. N.M. is funded by the German Research Foundation SFB TRR 219 (projects M‐03 and M‐05), reports giving lectures for and receiving honoraria from Amgen, Boehringer Ingelheim, Sanofi‐Aventis, Merck Sharp & Dohme, Bristol‐Myers Squibb, AstraZeneca, Lilly, Novo Nordisk, receiving unrestricted research grants from Boehringer Ingelheim; serving as an advisor for Amgen, Bayer, Boehringer Ingelheim, Sanofi‐Aventis, Merck Sharp & Dohme, Bristol‐Myers Squibb, AstraZeneca and Novo Nordisk, serving in trial leadership for Boehringer Ingelheim and Novo Nordisk, and declining all personal compensation from pharmaceutical and device companies. D.K.M. reports receiving personal fees from Boehringer Ingelheim, Janssen Research and Development LLC, Sanofi, CSL Behring, Merck Sharp & Dohme, Eli Lilly USA, Novo Nordisk, GlaxoSmithKline, AstraZeneca, Lexicon, Eisai, Esperion, Pfizer, Metavant and Applied Therapeutics. K.R.A., M.M., A.K. and M.W. are employees of Boehringer Ingelheim. O.E.J. was an employee of Boehringer Ingelheim at the time of study conduct, but is now employed by Nestl{\'e} Health Science. Funding Information: Data from this study were presented at the Virtual 80th Scientific Sessions of the American Diabetes Association, June 12?16, 2020. Funding Information: The CAROLINA trial was funded by Boehringer Ingelheim. Medical writing assistance, supported financially by Boehringer Ingelheim, was provided by Giles Brooke, PhD, CMPP, of Elevate Scientific Solutions during the preparation of this manuscript. Funding information Publisher Copyright: {\textcopyright} 2020 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.",
year = "2021",
month = feb,
doi = "10.1111/dom.14254",
language = "English (US)",
volume = "23",
pages = "569--580",
journal = "Diabetes, Obesity and Metabolism",
issn = "1462-8902",
publisher = "Wiley-Blackwell",
number = "2",
}