952-P: Incident and Recurrent Hypoglycemia with Linagliptin and Glimepiride in the CAROLINA Trial

Abstract

Treatment guideline recommendations for individuals with cardiovascular (CV) disease and type 2 diabetes (T2D) focus on medications with proven CV benefits. However, considerations relating to avoidance of hypoglycemia (HYPO) remain important. We report in the CARdiovascular Outcome Study of LINAgliptin Versus Glimepiride in Type 2 Diabetes (CAROLINA) the effects of treatment on a range of HYPO outcomes. CAROLINA recruited adults with relatively early T2D, HbA1c 6.5-8.5%, and elevated CV risk who were randomized to linagliptin 5 mg (LINA) or glimepiride 1-4 mg (GLIM) once daily added to usual care. Time to first or sum of first plus recurrent HYPO was assessed across categories: any, symptomatic with BG ≤70 mg/dL or severe, BG <54 mg/dL or severe, severe, or, leading to hospitalization, using Cox proportional hazards models or negative binomial regression. 6033 participants (mean age 64.0 years, HbA1c 7.2%, median T2D duration 6.3 years, 42% with CV disease) were followed for median 6.3 years. HbA1c over time did not differ between groups, but a significantly lower frequency of HYPO events was observed with LINA (Fig), regardless of definition, a difference further accentuated when including recurrent HYPO. In conclusion, these data demonstrate that LINA, compared with GLIM, has a significantly lower HYPO burden. Given the potentially harmful clinical impact of HYPO, these data may help inform therapy selection. Disclosure 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. 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. O. Johansen: Employee; Self; Boehringer Ingelheim International GmbH. M. Hoeiberg: Employee; Self; Boehringer Ingelheim International GmbH. E. Pfarr: None. M. Mattheus: None. T. Meinicke: None. J.T. George: Employee; Self; Boehringer Ingelheim International GmbH. M. Espeland: Other Relationship; Self; Boehringer Ingelheim International GmbH, Ironwood Pharmaceuticals. 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. 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. S.E. Kahn: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Intarcia Therapeutics, Janssen Scientific Affairs, LLC., Merck & Co., Inc., Novo Nordisk A/S, Pfizer Inc. Funding Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance