Glucose-lowering drugs or strategies and cardiovascular outcomes in patients with or at risk for type 2 diabetes: a meta-analysis of randomised controlled trials

被引:198
作者
Udell, Jacob A. [1 ,2 ,3 ]
Cavender, Matthew A. [4 ]
Bhatt, Deepak L. [4 ]
Chatterjee, Saurav [5 ]
Farkouh, Michael E. [3 ]
Scirica, Benjamin M. [4 ]
机构
[1] Univ Toronto, Womens Coll, Res Inst, Toronto, ON, Canada
[2] Univ Toronto, Dept Med, Womens Coll Hosp, Div Cardiovasc, Toronto, ON, Canada
[3] Univ Toronto, Peter Munk Cardiac Ctr, Univ Hlth Network, Heart & Stroke Richard Lewar Ctr Excellence, Toronto, ON, Canada
[4] Harvard Univ, Brigham & Womens Hosp, Div Cardiovasc, Sch Med, Boston, MA 02115 USA
[5] Mt Sinai Hlth Syst, St Lukes Roosevelt Hosp, Div Cardiol, New York, NY USA
关键词
CONGESTIVE-HEART-FAILURE; DIPEPTIDYL PEPTIDASE-4 INHIBITORS; ACUTE MYOCARDIAL-INFARCTION; LIFE-STYLE INTERVENTION; GLYCEMIC CONTROL; INSULIN-TREATMENT; FASTING GLUCOSE; CLINICAL-TRIALS; MELLITUS; DISEASE;
D O I
10.1016/S2213-8587(15)00044-3
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background Some glucose-lowering drugs or strategies adversely affect cardiovascular outcomes. We aimed to assess the extent to which glucose lowering by various drugs or strategies increases the risk of heart failure in patients with or at risk for type 2 diabetes, and to establish whether risk is associated with achieved differences in glycaemia or weight control. Methods We searched Ovid Medline, the Cochrane Library, and meeting abstracts up to Feb 20, 2015, for large randomised controlled trials of glucose-lowering drugs or strategies that assessed cardiovascular outcomes. The primary endpoint was incidence of heart failure. We derived pooled risk ratios (RRs) with random-effects models. Findings We included data from 14 trials, with mean duration 4.3 (2.3) years, comprising 95 502 patients, of whom 3907 (4%) patients developed a heart failure event. Glucose-lowering drugs or strategies were associated with a 0.50% (SD 0.33) reduction in HbA(1c) and a 1.7 kg (2.8) weight gain. Overall, glucose-lowering drugs or strategies increased the risk of heart failure compared with standard care (RR 1.14, 95% CI 1.01-1.30; p=0.041). The magnitude of this effect varied dependent on the method of glucose lowering (p for interaction=0.00021). Across drug classes, risk was highest with peroxisome proliferator-activated receptor agonists (RR 1.42, 95% CI 1.15-1.76; six trials), intermediate with dipeptidyl peptidase-4 inhibitors (1.25, 1.08-1.45; two trials), and neutral with insulin glargine (0.90, 0.77-1.05; one trial). Target-based intensive glycaemic control strategies (RR 1.00, 95% CI 0.88-1.13; four trials) and intensive weight loss (0.80, 95% CI 0.62-1.04; one trial) were also not associated with development of heart failure. Meta-regression analysis showed that for every 1.0 kg of weight gain associated with glucose-lowering drugs or strategies, there was a 7.1% (95% CI 1.0-13.6) relative increase in the risk of heart failure compared with standard care (p=0.022). Interpretation Compared with standard care, glycaemic lowering by various drugs or strategies might increase the risk of heart failure, with the magnitude of risk dependent on the method of glucose lowering and, potentially, weight gain.
引用
收藏
页码:356 / 366
页数:11
相关论文
共 65 条
[31]   ROLE OF DIABETES IN CONGESTIVE HEART-FAILURE - FRAMINGHAM STUDY [J].
KANNEL, WB ;
HJORTLAND, M ;
CASTELLI, WP .
AMERICAN JOURNAL OF CARDIOLOGY, 1974, 34 (01) :29-34
[32]   Systematic Review: Glucose Control and Cardiovascular Disease in Type 2 Diabetes [J].
Kelly, Tanika N. ;
Bazzano, Lydia A. ;
Fonseca, Vivian A. ;
Thethi, Tina K. ;
Reynolds, Kristi ;
He, Jiang .
ANNALS OF INTERNAL MEDICINE, 2009, 151 (06) :394-W130
[33]  
Knowler William C, 2002, N Engl J Med, V346, P393, DOI 10.1056/NEJMoa012512
[34]   Congestive heart failure and cardiovascular death in patients with prediabetes and type 2 diabetes given thiazolidinediones: a meta-analysis of randomised clinical trials [J].
Lago, Rodrigo M. ;
Singh, Premranjan P. ;
Nesto, Richard W. .
LANCET, 2007, 370 (9593) :1129-1136
[35]   Effect of Aleglitazar on Cardiovascular Outcomes After Acute Coronary Syndrome in Patients With Type 2 Diabetes Mellitus The AleCardio Randomized Clinical Trial [J].
Lincoff, A. Michael ;
Tardif, Jean-Claude ;
Schwartz, Gregory G. ;
Nicholls, Stephen J. ;
Ryden, Lars ;
Neal, Bruce ;
Malmberg, Klas ;
Wedel, Hans ;
Buse, John B. ;
Henry, Robert R. ;
Weichert, Arlette ;
Cannata, Ruth ;
Svensson, Anders ;
Volz, Dietmar ;
Grobbee, Diederick E. .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2014, 311 (15) :1515-1525
[36]  
Malmberg K, 1996, EUR HEART J, V17, P1337
[37]   FASTTRACK Intense metabolic control by means of insulin in patients with diabetes mellitus and acute myocardial infarction (DIGAMI 2):: effects on mortality and morbidity [J].
Malmberg, K ;
Rydén, L ;
Wedel, H ;
Birkeland, K ;
Bootsma, A ;
Dickstein, K ;
Efendic, S ;
Fisher, M ;
Hamsten, A ;
Herlitz, J ;
Hildebrandt, P ;
MacLeod, K ;
Laakso, M ;
Torp-Pedersen, C ;
Waldenström, A .
EUROPEAN HEART JOURNAL, 2005, 26 (07) :650-661
[38]   Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus [J].
Malmberg, K .
BRITISH MEDICAL JOURNAL, 1997, 314 (7093) :1512-1515
[39]   The Association of Hemoglobin A1c With Incident Heart Failure Among People Without Diabetes: The Atherosclerosis Risk in Communities Study [J].
Matsushita, Kunihiro ;
Blecker, Saul ;
Pazin-Filho, Antonio ;
Bertoni, Alain ;
Chang, Patricia P. ;
Coresh, Josef ;
Selvin, Elizabeth .
DIABETES, 2010, 59 (08) :2020-2026
[40]   Heart failure: a cardiovascular outcome in diabetes that can no longer be ignored [J].
McMurray, John J. V. ;
Gerstein, Hertzel C. ;
Holman, Rury R. ;
Pfeffer, Marc A. .
LANCET DIABETES & ENDOCRINOLOGY, 2014, 2 (10) :843-851