Effect of linagliptin, a dipeptidyl peptidase-4 inhibitor, compared with the sulfonylurea glimepiride on cardiovascular outcomes in Asians with type 2 diabetes: subgroup analysis of the randomized CAROLINA® trial.

Kadowaki, Takashi; Wang, Guang; Rosenstock, Julio; Yabe, Daisuke; Peng, Yongde; Kanasaki, Keizo; Mu, Yiming; Mattheus, Michaela; Keller, Annett; Okamura, Tomoo; Johansen, Odd Erik; Marx, Nikolaus

Kadowaki, Takashi; Wang, Guang; Rosenstock, Julio; Yabe, Daisuke; Peng, Yongde; Kanasaki, Keizo; Mu, Yiming; Mattheus, Michaela; Keller, Annett; Okamura, Tomoo; Johansen, Odd Erik; Marx, Nikolaus.

Afiliação

Kadowaki T; Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470 Japan.
Wang G; Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Rosenstock J; Dallas Diabetes Research Center at Medical City and University of Texas Southwestern Medical Center, Dallas, TX USA.
Yabe D; Department of Diabetes and Endocrinology, Gifu University Graduate School of Medicine, Gifu, Japan.
Peng Y; Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kobe, Japan.
Kanasaki K; Division of Molecular and Metabolic Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe, Japan.
Mu Y; Department of Endocrinology and Metabolism, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Mattheus M; Internal Medicine 1, Faculty of Medicine, Shimane University, Shimane, Japan.
Keller A; Division of Anticipatory Molecular Food Science and Technology, Medical Research Institute, Kanazawa Medical University, Ishikawa, Japan.
Okamura T; Department of Endocrinology, Chinese People's Liberation Army General Hospital, Beijing, China.
Johansen OE; Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
Marx N; Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.

Diabetol Int ; 12(1): 87-100, 2021 Jan.

Article em En | MEDLINE | ID: mdl-33479584

ABSTRACT

ABSTRACT

OBJECTIVE:

Linagliptin, a dipeptidyl peptidase-4 inhibitor, recently demonstrated cardiovascular (CV) safety versus placebo in Asians with advanced type 2 diabetes mellitus (T2DM) in the CARMELINA® trial. We assessed its CV safety compared with the sulfonylurea glimepiride in Asians with relatively early T2DM in the CAROLINA® trial.

METHODS:

Based on prespecified and post hoc subgroup analyses of the multinational CAROLINA® trial in which adults with relatively early T2DM and elevated CV risk were randomized to linagliptin or glimepiride added to usual care, we analyzed data for participants from Asian countries. This included the primary outcome defined as time to first CV death, non-fatal myocardial infarction, or non-fatal stroke [three-point major adverse cardiovascular events (3P-MACE)].

RESULTS:

Of the 6033 participants, 933 (15.5%) were from Asia. During a median follow-up of 6.2 years, 3P-MACE occurred in 9.5% and 11.1% of the linagliptin and glimepiride groups, respectively (hazard ratio [HR] 0.85; 95% confidence interval [CI] 0.57-1.26]), consistent with the overall population (HR 0.98; 95% CI 0.84-1.13; P = 0.17 for treatment by region interaction). Similarly, there were no significant differences between groups for other outcomes, including CV death (HR 0.73; 95% CI 0.38-1.38), non-CV mortality (HR 0.76; 95% CI 0.37-1.57) and hospitalization for heart failure (HR 0.89; 95% CI 0.36-2.19). Hypoglycemia adverse events occurred in 13.1% of linagliptin patients versus 42.1% of glimepiride patients (HR 0.25; 95% CI 0.19-0.33; P < 0.0001) despite similar glycemic control. Body weight was slightly lower with linagliptin relative to glimepiride weighted average mean difference over 256 weeks of - 1.82 kg (95% CI - 2.28 to - 1.35).