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

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.

Letter by Fung et al Regarding Article, “Frailty and Clinical Outcomes in Heart Failure: A Systematic Review and Meta-analysis”

2018 ◽  
Vol 19 (12) ◽  
pp. 1143-1146
Author(s):  
Erik Fung ◽  
Xiaobo Yang ◽  
Phillip J. Newton ◽  
Caleb Ferguson ◽  
Paloma Gastelurrutia ◽  
...  
Keyword(s):  
Heart Failure ◽  
Systematic Review ◽  
Clinical Outcomes ◽  
Meta Analysis

scholarly journals The safety and efficacy of SDLT-2 (Sodium-glucose co-transporter 2) inhibitor versus placebo in the treatment of heart failure in patients with or without T2DM (Type 2 diabetes mellitus): A Systemic Review and Meta-analysis.

2020 ◽  
Author(s):  
Qian Zhang ◽  
Xiaofei Wang ◽  
Peipei Ge ◽  
Aizhen Hu ◽  
Xuexun Li
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Sglt2 Inhibitor ◽  
Systemic Review ◽  
Cochrane Library ◽  
Volume Depletion ◽  
Patients With Heart Failure ◽  
Safety Outcomes

Abstract Background Sodium-glucose co-transporter 2 (SGLT2) inhibitor which is a type of drug used for the treatment of diabetes mellitus, has been reported by many trials that it could be beneficial for patients with established heart failure. A meta-analysis on this subject could obtain more reliable estimates of the efficacy and safety outcomes. Methods A systematic review and meta-analysis of randomized, placebo-controlled trials of SGLT2 inhibitor in patients with heart failure was conducted. We searched PubMed, Cochrane Library, and Web of Science for trials published from inception to March, 2018. PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) was used to conduct the review. For quality assessment of included studies. The methodological quality of the included trials was assessed using the Cochrane tool for assessing randomized clinical trials (RCT). Efficacy outcomes included hospitalization for heart failure and all-cause death. Safety outcomes consisted of serious adverse event (SAE) and volume depletion. Results We included data from 5 identified studies and 8775 patients (aged 64.9, female 29.8%). A total of 3930 (44.8%) patients were known to have diabetes mellitus. Compared with placebo, SGLT2 inhibitor decrease the incidence of hospitalization for heart failure (RR 0.692; 95%CI, 0.611-0.784 P<0.001), and all-cause death (RR 0.824; 95%CI, 0.736-0.922 P=0.001). The incidence of SAE in patients with a treatment of SGLT2 inhibitor was low (RR 0.869; 95%CI, 0.779-0.970 P=0.012). SGLT2 inhibitor didn’t increase the incidence of volume depletion (RR1.165, 95%CI, 0.977-1.390 P=0.089). Conclusion Our results confirm that SGLT2 inhibitor is effective and safe for patients with heart failure regardless of presence of diabetes mellitus.

Pioglitazone for the Primary and Secondary Prevention of Cardiovascular and Renal Outcomes in Patients with or at High Risk of Type 2 Diabetes Mellitus: A Meta-Analysis

2019 ◽  
Vol 105 (5) ◽  
pp. 1670-1681 ◽  
Author(s):  
Yue Zhou ◽  
Yajing Huang ◽  
Xiaoyun Ji ◽  
Xiang Wang ◽  
Liyan Shen ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Myocardial Infarction ◽  
Heart Failure ◽  
High Risk ◽  
Meta Analysis ◽  
Cardiovascular Death ◽  
Primary And Secondary Prevention ◽  
All Cause Mortality ◽  
History Of

Abstract Context The goal of the meta-analysis was to evaluate the effect of pioglitazone on the primary and secondary prevention of cardiovascular diseases (CVDs) and renal adverse events in patients with or at high risk of type 2 diabetes mellitus (T2DM). Design Randomized controlled trials (RCTs) comparing pioglitazone with any control were identified through PubMed, Embase, and the Cochrane Library. Cardiovascular outcomes included major adverse cardiovascular events (MACEs, defined as the composite of nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death), hospitalization for heart failure, and all-cause mortality. Renal outcomes included change in urinary albumin to creatinine ratio and 24-hour urinary protein excretion. Weighted mean difference (WMD) and risk ratio (RR) with 95% confidence intervals (CIs) were pooled. Results A total of 26 studies with 19 645 participants were enrolled. Pioglitazone reduced the risk of MACE (RR, 0.8 [95% CI, 0.7–0.9]), with benefit only seen in patients with a history of established CVDs (0.8 [0.7–0.9]) and not in those without (1.0 [0.7–1.3]). Regarding the individual components, pioglitazone reduced the risk of nonfatal myocardial infarction (0.8 [0.6–1.0]) and nonfatal stroke (0.8 [0.7–0.9]), which was confined to patients with a history of established CVDs, whereas no treatment effect was found on cardiovascular death (1.0 [0.7–1.2]) regardless of the presence of established CVDs. Pioglitazone increased the risk of hospitalization for heart failure (1.3 [1.1–1.6]) and had no treatment effect on all-cause mortality (1.0 [0.8–1.1]). Pioglitazone reduced albuminuria by 18.5% (WMD 18.5% [95% CI, 21.1-16.0]), with a similar benefit in patients with different renal function categories. Conclusions Pioglitazone should be considered in patients with or at high risk of T2DM for the prevention of cardiovascular endpoints, especially in those with a history of established CVD who might benefit the most. Robust reductions in progression of renal disease are seen regardless of baseline renal function degree.

P960Association of peri-procedural intravenous morphine use on clinical outcomes in ST-elevation myocardial infarction treated by percutaneous coronary intervention: systematic review and meta-analysis

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
R Batchelor ◽  
D Liu ◽  
J Bloom ◽  
S Noaman ◽  
W Chan
Keyword(s):  
Myocardial Infarction ◽  
Systematic Review ◽  
Percutaneous Coronary Intervention ◽  
Clinical Outcomes ◽  
Odds Ratio ◽  
Meta Analysis ◽  
Coronary Intervention ◽  
Increased Risk ◽  
Percutaneous Coronary ◽  
St Elevation

Abstract Background Morphine analgesia may affect absorption of co-prescribed P2Y12 antagonists attenuating platelet inhibition. The impact of peri-procedural intravenous (IV) morphine administration on clinical outcomes in patients undergoing primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction (STEMI) is not well defined. Purpose To conduct a systematic review and meta-analysis exploring clinical outcomes with peri-procedural IV morphine in patients undergoing PPCI for STEMI. Methods Analysis of the electronic databases MEDLINE, EMBASE, CENTRAL, Scopus, Web of Science and ClinicalTrials.gov for association of peri-PCI IV morphine use with myocardial infarction (MI) and mortality. Primary and secondary outcomes were in-hospital or 30-day MI and all-cause mortality respectively. Results Eleven studies (1 randomised controlled trial; 10 cohort studies) were included for systematic review. Five studies, including 3,748 patients were included in meta-analysis of the primary outcome. Of 3,748 patients, 2,239 were treated concurrently with ticagrelor, 1,256 treated with clopidogrel and 253 with prasugrel. As shown in the Figure, there was a trend towards increased risk of myocardial infarction with IV morphine (odds ratio 1.88; 95% CI 0.87–4.09, I2 0%). Across seven studies and 6585 patients, no increased risk of mortality at the same composite time endpoint was evident (odds ratio 0.70, 95% CI 0.40–1.23, I2 19%). Figure 1. MI in hospital or at 30 days Conclusion Based on current literature, evidence of an association between IV morphine and myocardial infarction in patients undergoing PPCI for STEMI is limited by observational methodology and conflicting results. There is no evidence of an association between intravenous peri-procedural morphine and mortality. Clinical trial evidence with strong documentation of adverse events data is required to demonstrate association or causality. Acknowledgement/Funding None

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