Diabetes mellitus, blood glucose and the risk of heart failure: A systematic review and meta-analysis of prospective studies

Abstract Background The most significant manifestation of heart failure is exercise intolerance. This systematic review and meta-analysis was performed to investigate whether dipeptidyl peptidase-4 (DPP-4) inhibitors or glucagon-like peptide 1 receptor agonists (GLP-1 RAs), widely used anti-diabetic drugs, could improve exercise tolerance in heart failure patients with or without type 2 diabetes mellitus. Methods An electronic search of PubMed, EMBASE and the Cochrane Library was carried out through March 8th, 2019, for eligible trials. Only randomized controlled studies were included. The primary outcome was exercise tolerance [6-min walk test (6MWT) and peak O2 consumption], and the secondary outcomes included quality of life (QoL), adverse events (AEs) and all-cause death. Result After the literature was screened by two reviewers independently, four trials (659 patients) conducted with heart failure patients with or without type 2 diabetes met the eligibility criteria. The results suggested that targeting the DPP-4-GLP-1 pathway can improve exercise tolerance in heart failure patients [MD 24.88 (95% CI 5.45, 44.31), P = 0.01] without decreasing QoL [SMD -0.51 (95% CI -1.13, 0.10), P = 0.10]; additionally, targeting the DPP-4-GLP-1 pathway did not show signs of increasing the incidence of serious AEs or mortality. Conclusion Our results suggest that DPP-4 inhibitors or GLP-1 RAs improve exercise tolerance in heart failure patients. Although the use of these drugs for heart failure has not been approved by any organization, they may be a better choice for type 2 diabetes mellitus patients with heart failure. Furthermore, as this pathway contributes to the improvement of exercise tolerance, it may be worth further investigation in exercise-intolerant patients with other diseases.

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Glycated hemoglobin as a surrogate for evaluating the effectiveness of drugs in diabetes mellitus trials: a systematic review and trial-level meta-analysis

International Journal of Technology Assessment in Health Care ◽

10.1017/s0266462321001689 ◽

2021 ◽

Vol 38 (1) ◽

Author(s):

Paola Andrea Rivera ◽

Milton J. M. Rodríguez-Zúñiga ◽

José Caballero-Alvarado ◽

Fabián Fiestas

Keyword(s):

Diabetes Mellitus ◽

Myocardial Infarction ◽

Heart Failure ◽

Systematic Review ◽

Clinical Outcomes ◽

Randomized Clinical Trials ◽

Glycated Hemoglobin ◽

Meta Analysis ◽

Strong Association ◽

Kidney Injury

Abstract Objective The objective of this study was to investigate whether glycated hemoglobin (HbA1c) is a valid surrogate for evaluating the effectiveness of antihyperglycemic drugs in diabetes mellitus (DM) trials. Methods We conducted a systematic review of placebo-controlled randomized clinical trials (RCTs) evaluating the effect of a treatment on HbA1c (mean difference between groups) and clinical outcomes (relative risk of mortality, myocardial infarction, stroke, heart failure, and/or kidney injury) in patients with DM. Then, we investigated the association between treatment effects on HbA1c and clinical outcomes using regression analysis at the trial level. Lastly, we interpreted the correlation coefficients (R) using the cut-off points suggested by the Institute for Quality and Efficiency in Healthcare (IQWiG). HbA1c was considered a valid surrogate if it demonstrated a strong association: lower limit of the 95 percent confidence interval (95 percent CI) of R greater than or equal to .85. Results Nineteen RCTs were identified. All studies included adults with type 2 DM. None of the associations evaluated was strong enough to validate HbA1c as a surrogate for any clinical outcome: mortality (R = .34; 95 percent CI −.14 to .69), myocardial infarction (R = .20; −.30 to .61), heart failure (R = .08; −.40 to .53), kidney injury (R = −.04; −.52 to .47), and stroke (R = .81; .54 to .93). Conclusions The evidence from multiple placebo-controlled RCTs does not support the use of HbA1c as a surrogate to measure the effectiveness of antihyperglycemic drugs in DM studies.

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Tobacco smoking and the risk of heart failure: A systematic review and meta-analysis of prospective studies

European Journal of Preventive Cardiology ◽

10.1177/2047487318806658 ◽

2018 ◽

Vol 26 (3) ◽

pp. 279-288 ◽

Cited By ~ 18

Author(s):

Dagfinn Aune ◽

Sabrina Schlesinger ◽

Teresa Norat ◽

Elio Riboli

Keyword(s):

Heart Failure ◽

Systematic Review ◽

Smoking Cessation ◽

Prospective Studies ◽

Meta Analysis ◽

Adjusted Relative Risk ◽

Increased Risk ◽

Quitting Smoking ◽

Former Smokers ◽

Never Smokers

Background We conducted a systematic review and meta-analysis to clarify the association between smoking and the risk of developing heart failure. Methods PubMed and Embase databases were searched up to 24 July 2018. Prospective studies were included if they reported adjusted relative risk (RR) estimates and 95% confidence intervals (CIs) of heart failure associated with smoking. Summary RRs and 95% CIs were estimated using a random effects model. Results Twenty-six studies were included. The summary RR was 1.75 (95% CI: 1.54–1.99, I2 = 81%, n = 10) for current smokers, 1.16 (95% CI: 1.08–1.24, I2 = 51%, n = 9) for former smokers, and 1.44 (1.34–1.55, I2 = 83%, n = 10) for ever smokers compared with never smokers. The summary RR was 1.41 (95% CI: 1.01–1.96, I2 = 82%, n = 2) per 10 cigarettes per day, 1.11 (95% CI: 1.04–1.18, I2 = 70%, n = 3) and 1.08 (95% CI: 1.02–1.14, I2 = 34%, n = 2) per 10 pack-years among ever smokers and former smokers, respectively, and 0.79 (95% CI: 0.63–1.00, I2 = 96%, n = 2) per 10 years since quitting smoking. The association between smoking cessation and heart failure reached significance at 15 years of smoking cessation, and at 30 years the summary RR was 0.72 (95% CI: 0.57–0.90), only slightly higher than the summary RR for never smokers (0.64 (95% CI: 0.57–0.72)) when compared with current smokers. Conclusion Smoking is associated with increased risk of heart failure, but the risk decreases with increasing duration since smoking cessation. Any further studies should investigate the association between number of cigarettes per day, duration, pack-years and time since quitting smoking and risk of heart failure.

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