1-OR: Analyses of First Plus Recurrent Cardiovascular (CV) and Hospitalization Events in the CAROLINA Trial
Authors: MARX NIKOLAUS , MCGUIRE DARREN K. , JOHANSEN ODD ERIK , ROSENSTOCK JULIO , PFARR EGON , MATTHEUS MICHAELA , GEORGE JYOTHIS T. , ESPELAND MARK , ZINMAN BERNARD 
Published: June 2020

CAROLINA® (CARdiovascular Outcome Study of LINAgliptin Versus Glimepiride in Type 2 Diabetes) was a randomized controlled clinical trial designed to compare the effects of linagliptin (LINA) with glimepiride (GLIM) on CV events and other outcomes in patients with relatively early type 2 diabetes (T2D) with elevated CV risk. To characterize the effects on net CV disease and hospitalization burden of this population, we assessed effects of LINA vs. GLIM on all first plus recurrent CV events and any-cause hospitalizations using a negative binomial model. A total of 6033 participants were enrolled (mean age 64.0 years, HbA1c 7.2%, BMI 30.1 kg/m2, eGFR 77 ml/min/1.73m2, median T2D duration 6.3 years, UACR 9 mg/g, 42% with CV disease, 4.5% with heart failure [HF]). Adding recurrent events increased the number of events for analysis from first event by 10 to 77% across CV/HF outcomes and by 119% for hospitalizations with corresponding increase in rates per 100-patient years in both treatment groups (e.g., 3P-MACE from 2.1 to 2.8 [LINA] and 2.1 to 2.9 [GLIM]), over median 6.3 years. Analyses of first-event and first plus recurrent events are presented (Fig).
In conclusion, no significant differences were observed between LINA or GLIM for either first or recurrent CV or hospitalization events. These data underscore the significant CV disease burden experienced even in relatively early T2D and reinforce the safety of LINA.

Disclosure
N. Marx: Other Relationship; Self; Amgen, AstraZeneca, Bayer Vital, Boehringer Ingelheim International GmbH, Daiichi Sankyo, Kowa Research Institute, Inc., Medtronic, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis. D.K. McGuire: Consultant; Self; Afimmune, Applied Therapeutics, Merck Sharp & Dohme Corp., Metavant. Other Relationship; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eisai Co., Ltd., Eli Lilly and Company, Esperion Therapeutics, Inc., GlaxoSmithKline plc., Janssen Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis. O. Johansen: Employee; Self; Boehringer Ingelheim International GmbH. J. Rosenstock: Research Support; Self; AstraZeneca, Bristol-Myers Squibb, Genentech, Inc., GlaxoSmithKline plc., Lexicon Pharmaceuticals, Inc., Oramed Pharmaceuticals, PegBio Co., Ltd., Pfizer Inc., REMD Biotherapeutics. Other Relationship; Self; Applied Therapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. E. Pfarr: None. M. Mattheus: None. J.T. George: Employee; Self; Boehringer Ingelheim International GmbH. M. Espeland: Other Relationship; Self; Boehringer Ingelheim International GmbH, Ironwood Pharmaceuticals. B. Zinman: Advisory Panel; Self; Abbott, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi-Aventis.

Funding
Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance