scholarly journals Sodium-glucose co-transporter inhibitors in insulin-treated diabetes: a meta-analysis

2021 ◽  
Author(s):  
Joao Pedro Ferreira ◽  
Ana Cristina Oliveira ◽  
Francisca A. Saraiva ◽  
Francisco Vasques-Nóvoa ◽  
Adelino Leite-Moreira
Keyword(s):  
Cardiovascular Events ◽  
Insulin Treatment ◽  
Meta Analysis ◽  
Cardiovascular Death ◽  
Major Adverse Cardiovascular Events ◽  
Significant Heterogeneity ◽  
Random Effects Models ◽  
Sodium Glucose Cotransporter ◽  
Q Statistic ◽  
Insulin Use

Background: Patients with insulin-treated type 2 diabetes (T2D) have a high risk of major adverse cardiovascular events. Sodium-glucose cotransporter inhibitors (SGLTi) improve outcomes without hypoglycemic risk. Aims: To study the effect of SGLTi in patients with T2D with and without background insulin-treatment in outcome-driven RCTs. Methods: Random effects models. Results: A total of 54,374 patients with T2D were included in the analysis, of which 26,551 (48.8%) were treated with insulin. For 3P-MACE in patients without insulin treatment, the HR (95%CI) for the effect of SGLTi vs. placebo was 0.93 (0.81-1.05), with moderate heterogeneity (I2 =49.2%, Q statistic P =0.11). In insulin-treated patients, the HR (95%CI) was 0.88 (0.82-0.95), without evidence of heterogeneity (I2 =0.0%, Q statistic P =0.91). The pooled effect evidenced a 10% reduction of 3P-MACE with SGLTi (HR 0.90, 95%CI 0.85-0.96), without SGLTi-by-insulin interactionP=0.53. For the composite outcome of HF hospitalisation or cardiovascular death in patients without insulin treatment, the HR (95%CI) for the effect of SGLTi vs. placebo was 0.77 (0.61-0.92), with marked heterogeneity (I2 =66.8%, Q statistic P =0.02). In insulin-treated patients, the HR (95%CI) was 0.77 (0.68-0.86), without significant heterogeneity (I2 =31.7%, Q statistic P =0.25). The pooled effect evidenced a 23% reduction of HF hospitalisations or cardiovascular death with SGLTi (HR 0.77, 95%CI 0.68-0.85), without SGLTi -by-insulin interactionP=0.98. Conclusion:SGLTi reduce cardiovascular events regardless of insulin use. However, the treatment effect is more homogeneous among insulin-treated patients, supporting the use of SGLTi for the treatment of patients with T2D requiring insulin for glycemic control.

scholarly journals Sodium glucose cotransporter 2 inhibitors and risk of major adverse cardiovascular events: multi-database retrospective cohort study

BMJ ◽  
2020 ◽  
pp. m3342 ◽  
Author(s):  
Kristian B Filion ◽  
Lisa M Lix ◽  
Oriana HY Yu ◽  
Sophie Dell’Aniello ◽  
Antonios Douros ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Events ◽  
Retrospective Cohort ◽  
Meta Analysis ◽  
Cardiovascular Death ◽  
Sglt2 Inhibitors ◽  
Major Adverse Cardiovascular Events ◽  
Site Specific ◽  
Sodium Glucose Cotransporter ◽  
All Cause Mortality

Abstract Objective To compare the risk of cardiovascular events between sodium glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors among people with type 2 diabetes in a real world context of clinical practice. Design Multi-database retrospective cohort study using a prevalent new user design with subsequent meta-analysis. Setting Canadian Network for Observational Drug Effect Studies (CNODES), with administrative healthcare databases from seven Canadian provinces and the United Kingdom, 2013-18. Population 209 867 new users of a SGLT2 inhibitor matched to 209 867 users of a DPP-4 inhibitor on time conditional propensity score and followed for a mean of 0.9 years. Main outcome measures The primary outcome was major adverse cardiovascular events (MACE, a composite of myocardial infarction, ischaemic stroke, or cardiovascular death). Secondary outcomes were the individual components of MACE, heart failure, and all cause mortality. Cox proportional hazards models were used to estimate site specific adjusted hazards ratios and 95% confidence intervals, comparing use of SGLT2 inhibitors with use of DPP-4 inhibitors in an as treated approach. Site specific results were pooled using random effects meta-analysis. Results Compared with DPP-4 inhibitors, SGLT2 inhibitors were associated with decreased risks of MACE (incidence rate per 1000 person years: 11.4 v 16.5; hazard ratio 0.76, 95% confidence interval 0.69 to 0.84), myocardial infarction (5.1 v 6.4; 0.82, 0.70 to 0.96), cardiovascular death (3.9 v 7.7; 0.60, 0.54 to 0.67), heart failure (3.1 v 7.7; 0.43, 0.37 to 0.51), and all cause mortality (8.7 v 17.3; 0.60, 0.54 to 0.67). SGLT2 inhibitors had more modest benefits for ischaemic stroke (2.6 v 3.5; 0.85, 0.72 to 1.01). Similar benefits for MACE were observed with canagliflozin (0.79, 0.66 to 0.94), dapagliflozin (0.73, 0.63 to 0.85), and empagliflozin (0.77, 0.68 to 0.87). Conclusions In this large observational study conducted in a real world clinical practice context, the short term use of SGLT2 inhibitors was associated with a decreased risk of cardiovascular events compared with the use of DPP-4 inhibitors. Trial registration ClinicalTrials.gov NCT03939624 .

scholarly journals The Effects of Dapagliflozin in Patients With Heart Failure Complicated With Type 2 Diabetes: A Meta-Analysis of Placebo-Controlled Randomized Trials

2021 ◽  
Vol 2 ◽  
Author(s):  
Miaobo Zhai ◽  
Xin Du ◽  
Changmei Liu ◽  
Huipu Xu
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Meta Analysis ◽  
Cardiovascular Death ◽  
Major Adverse Cardiovascular Events ◽  
Significant Heterogeneity ◽  
Sodium Glucose Cotransporter ◽  
All Cause Mortality ◽  
Incidence Of Hospitalization

BackgroundCardiovascular disease threatens the health and quality of life of individuals, particularly those with type II diabetes. Recently, some studies have reported the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors in reducing the rates of hospitalization or urgent visits, resulting in IV therapy for heart failure in patients with type 2 diabetes mellitus (T2DM).MethodsWe did a comprehensive search in electronic databases from inception through July 2020 for randomized-controlled trials, using the keywords “sodium-glucose cotransporter-2 inhibitor”, “dapagliflozin”, “heart failure”, “cardiovascular outcomes”, “major adverse cardiovascular events”, “all-cause mortality”, and “cardiovascular death”. Random-effects summary odds ratios (OR) were constructed using M-L heterogeneity model.ResultsFive trials with 5,252 patients were ultimately included. The incidence of hospitalization for heart failure (HHF) (n=4, OR=0.74; 95% CI, 0.61 to 0.88; I2 = 0%) and all-cause mortality (ACM, n=4, OR=0.76; 95% CI, 0.66 to 0.94; I2 = 0%); was reduced by dapagliflozin, respectively, in all heart failure patients, without obvious heterogeneity. The incidence of cardiovascular death in dapagliflozin was lower than that in placebo without statistically significant (CVD, n=5, OR=0.84; 95% CI, 0.69 to 1.03; I2 = 0%). In HFrEF subgroup, dapagliflozin was associated with a reduced incidence of hospitalization for heart failure (n=4, OR=0.74; 95% CI, 0.60 to 0.91; I2 = 0%), cardiovascular death (n=4, OR=0.72; 95% CI, 0.58 to 0.91; I2 = 8%), and all-cause mortality (n=3, OR=0.70; 95% CI, 0.50 to 0.99; I2 = 43%) without significant heterogeneity. In contrast, in the HFpEF subgroup, there was no difference in the incidence of cardiovascular death (n=2, OR=1.45; 95% CI, 0.95 to 2.22; I2 = 0%) and all-cause mortality (n=2, OR=1.04; 95% CI, 0.76 to 1.43; I2 = 0%) between dapagliflozin and placebo.ConclusionIn our study, dapagliflozin performed a statistical reduction in the rate of heart failure hospitalization, cardiovascular death, and all-cause mortality in patients with HFrEF and diabetes. However, in the HFpEF subgroup, dapagliflozin did not show a significant cardiovascular protective effect.

scholarly journals Early Change in Albuminuria with Canagliflozin Predicts Kidney and Cardiovascular Outcomes: A PostHoc Analysis from the CREDENCE Trial

2020 ◽  
Vol 31 (12) ◽  
pp. 2925-2936 ◽  
Author(s):  
Megumi Oshima ◽  
Brendon L. Neuen ◽  
JingWei Li ◽  
Vlado Perkovic ◽  
David M. Charytan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Cardiovascular Events ◽  
Renin Angiotensin System ◽  
Cardiovascular Death ◽  
Cardiovascular Outcomes ◽  
Major Adverse Cardiovascular Events ◽  
Early Change ◽  
Sodium Glucose Cotransporter

BackgroundThe association between early changes in albuminuria and kidney and cardiovascular events is primarily based on trials of renin-angiotensin system blockade. It is unclear whether this association occurs with sodium-glucose cotransporter 2 inhibition.MethodsThe Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial enrolled 4401 patients with type 2 diabetes and CKD (urinary albumin-creatinine ratio [UACR] >300 mg/g). This post hoc analysis assessed canagliflozin’s effect on albuminuria and how early change in albuminuria (baseline to week 26) is associated with the primary kidney outcome (ESKD, doubling of serum creatinine, or kidney death), major adverse cardiovascular events, and hospitalization for heart failure or cardiovascular death.ResultsComplete data for early change in albuminuria and other covariates were available for 3836 (87.2%) participants in the CREDENCE trial. Compared with placebo, canagliflozin lowered UACR by 31% (95% confidence interval [95% CI], 27% to 36%) at week 26, and significantly increased the likelihood of achieving a 30% reduction in UACR (odds ratio, 2.69; 95% CI, 2.35 to 3.07). Each 30% decrease in UACR over the first 26 weeks was independently associated with a lower hazard for the primary kidney outcome (hazard ratio [HR], 0.71; 95% CI, 0.67 to 0.76; P<0.001), major adverse cardiovascular events (HR, 0.92; 95% CI, 0.88 to 0.96; P<0.001), and hospitalization for heart failure or cardiovascular death (HR, 0.86; 95% CI, 0.81 to 0.90; P<0.001). Residual albuminuria levels at week 26 remained a strong independent risk factor for kidney and cardiovascular events, overall and in each treatment arm.ConclusionsIn people with type 2 diabetes and CKD, use of canagliflozin results in early, sustained reductions in albuminuria, which were independently associated with long-term kidney and cardiovascular outcomes.

scholarly journals Clinical Efficacy of Sodium-Glucose Co-Transporter-2 (SGLT2) Inhibitor in Cardiovascular Outcomes Among Patients with and Without Heart Failure: A Systematic Review and Meta-Analysis

2021 ◽  
Author(s):  
Mei-Chuan Lee ◽  
Yi-Ming Hua ◽  
Chun-Ting Yang ◽  
Wei-Ting Chang ◽  
Fang-Hsiu Kuo ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Clinical Efficacy ◽  
Cardiovascular Events ◽  
Meta Analysis ◽  
Sglt2 Inhibitor ◽  
Cardiovascular Death ◽  
Sglt2 Inhibitors ◽  
Major Adverse Cardiovascular Events ◽  
All Cause Mortality ◽  
Clinical Benefits

Abstract BackgroundHeart failure (HF) has become a healthcare challenge worldwide. Recently, certain trials on sodium-glucose co-transporter-2 (SGLT2) inhibitor showed benefits for patients with HF. This study aimed to systematically review the literature and investigate the clinical efficacy of SGLT2 inhibitors in cardiovascular events among patients with and without HF. Methods We searched randomized controlled trials (RCTs) in PubMed, Cochrane databases, Embase, and ClinicalTrials.gov registry form inception to October 2020. Dichotomous variables were pooled using a random-effects model and presented with a risk ratio (RR) and 95% confidence interval (CI). Subgroup meta-analyses were carried out by high/low SGLT2/SGLT1 selectivity and individual SGLT2 inhibitor.ResultsA total of 10 RCTs comprised of 52,607 patients were eligible for the analyses. SGLT2 inhibitors reduced the risk of total cardiovascular death or hospitalization for HF (RR 0.79, [95% CI: 0.74 to 0.84]; p < 0.01, I2 = 31%). Apart from stroke, SGLT2 inhibitors contributed to a risk reduction in major adverse cardiovascular events (MACE, RR 0.93, [95% CI: 0.88 to 0.99]; p = 0.03, I2 = 0), all-cause mortality (RR 0.92, [95% CI: 0.85 to 0.99]; p = 0.03, I2 = 0), cardiovascular death (RR 0.91, [95% CI: 0.83 to 0.99]; p = 0.03, I2 = 0), hospitalization for HF (RR 0.72, [95% CI: 0.66 to 0.79]; p < 0.01, I2 = 0), and myocardial infarction (RR 0.89, [95% CI: 0.80 to 0.99]; p = 0.03, I2 = 0). For HF patients, SGLT2 inhibitors had more clinical benefits in terms of all-cause mortality and cardiovascular death, while advantages were observed in MACE and myocardial infarction for non-HF patients. Furthermore, SGLT2 inhibitors with low SGLT2/SGLT1 selectivity have better efficacy for hospitalization of HF, compared with high-selectivity inhibitors (RR 0.51 [95% CI: 0.35-0.75] versus 0.73 [95% CI: 0.66-0.81] for HF patients). ConclusionsSGLT2 inhibitors significantly mitigate hospitalization for HF. Between HF and non-HF populations, this regimen reduce mortality for HF patients and improve MACE and myocardial infarction for non-HF patients. The SGLT2 inhibitor, mixed with the effect of SGLT1 inhibitors, may lead to a lower risk of hospitalization for HF.

scholarly journals The Association between Baseline Insulin Treatment and Cardiovascular Events: A Meta-Analysis

2020 ◽  
Author(s):  
Joanna E Khatib ◽  
Yixue Shao ◽  
Lizheng Shi ◽  
Vivian A Fonseca
Keyword(s):  
Treatment Group ◽  
Cardiovascular Events ◽  
Meta Analysis ◽  
New Drugs ◽  
Major Adverse Cardiovascular Events ◽  
Insulin Regimen ◽  
Antidiabetic Drug ◽  
Number Of Patients ◽  
Insulin Use

Abstract We conducted a meta-analysis to compare major adverse cardiovascular events (MACE) in recent diabetes type 2 drugs cardiovascular outcome trials (CVOTs) in the subgroups that used insulin at baseline to the subgroups that did not. English publications from 2010 to 2019 were searched in PubMed and Google Scholar. We searched published clinical trials for CVOTs with new drugs for type 2 diabetes and found 12 publications, of which 8 provided outcomes according to insulin use. We compared the event rate of the primary outcome in the group taking insulin with the one not taking insulin. Data was extracted by two investigators independently including: CVOT drug, publication year, sample size, duration of diabetes, mean hemoglobin A1c, mean age, number of patients in each treatment group. We included 8 trials in the analysis: DECLARE, EMPAREG, EXSCEL, HARMONY, LEADER, SUSTAIN6, EXAMINE, and SAVOR-TIMI. The pooled relative risk was 1.52 (95% CI: 1.43~1.62) when comparing the treatment group with insulin at baseline with the treatment group of patients without insulin use. In recent CVOTs, patient on Insulin regimen along with the new antidiabetic drug had higher RR of cardiovascular events than patients who used the new antidiabetic drug alone.

scholarly journals Relation of insulin treatment for type 2 diabetes to the risk of major adverse cardiovascular events after acute coronary syndrome: an analysis of the BETonMACE randomized clinical trial

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Gregory G. Schwartz ◽  
Stephen J. Nicholls ◽  
Peter P. Toth ◽  
Michael Sweeney ◽  
Christopher Halliday ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Events ◽  
Insulin Treatment ◽  
Hdl Cholesterol ◽  
Major Adverse Cardiovascular Events ◽  
Evidence Based ◽  
Coronary Syndrome ◽  
Low Hdl ◽  
Insulin Use

Abstract Background In stable patients with type 2 diabetes (T2D), insulin treatment is associated with elevated risk for major adverse cardiovascular events (MACE). Patients with acute coronary syndrome (ACS) and T2D are at particularly high risk for recurrent MACE despite evidence-based therapies. It is uncertain to what extent this risk is further magnified in patients with recent ACS who are treated with insulin. We examined the relationship of insulin use to risk of MACE and modification of that risk by apabetalone, a bromodomain and extra-terminal (BET) protein inhibitor. Methods The analysis utilized data from the BETonMACE phase 3 trial that compared apabetalone to placebo in patients with T2D, low HDL cholesterol, andACS. The primary MACE outcome (cardiovascular death, myocardial infarction, or stroke) was examined according to insulin treatment and assigned study treatment. Multivariable Cox regression was used to determine whether insulin use was independently associated with the risk of MACE. Results Among 2418 patients followed for median 26.5 months, 829 (34.2%) were treated with insulin. Despite high utilization of evidence-based treatments including coronary revascularization, intensive statin treatment, and dual antiplatelet therapy, the 3-year incidence of MACE in the placebo group was elevated among insulin-treated patients (20.4%) compared to those not-treated with insulin (12.8%, P = 0.0001). Insulin treatment remained strongly associated with the risk of MACE (HR 2.10, 95% CI 1.42–3.10, P = 0.0002) after adjustment for demographic, clinical, and treatment variables. Apabetalone had a consistent, favorable effect on MACE in insulin-treated and not insulin-treated patients. Conclusion Insulin-treated patients with T2D, low HDL cholesterol, and ACS are at high risk for recurrent MACE despite the use of evidence-based, contemporary therapies. A strong association of insulin treatment with risk of MACE persists after adjustment for other characteristics associated with MACE. There is unmet need for additional treatments to mitigate this risk. Trial registration ClinicalTrials.gov NCT02586155, registered October 26, 2015

scholarly journals Effect of somatometric parameters on the prevalence and severity of varicocele: a systematic review and meta-analysis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Runqing Li ◽  
Junjie Liu ◽  
Yushan Li ◽  
Quanxian Wang
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Cochrane Library ◽  
China National Knowledge Infrastructure ◽  
Random Effects Models ◽  
Knowledge Infrastructure ◽  
Regression Test ◽  
Mean Differences ◽  
Q Statistic ◽  
The Relationship

Abstract Background Published studies have shown contradictory results regarding the relationship between somatometric parameters and varicoceles. We performed a systematic review and meta-analysis to investigate the possible effects of age, height, weight, and body mass index (BMI) on the presence and severity of varicoceles. Methods Databases including EMBASE, MEDLINE, PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), Web of Science, and Google Scholar were systematically searched to identify relevant articles published up to March 2020. Two researchers independently identified eligible articles and extracted data. Cochran’s Q statistic and I2 statistics were used to assess heterogeneity. Meta-analysis was performed using StataSE 12.0 software (StataCorp LP, USA). Random-effects models were used to obtain the weighted mean differences (WMDs) and 95% confidence intervals (CIs). Publication bias was assessed using Begg’s funnel plot and Egger’s regression test. Results The search strategy produced 272 articles, of which 18 articles were eligible according to the inclusion/exclusion criteria. A total of 56,325 patients with varicocele and 1,334,694 patients without varicocele were included in the meta-analysis to evaluate the effect of somatometric parameters on the presence and severity of varicocele. The overall results demonstrated that the presence of varicoceles was significantly associated with height (WMD = 1.41, 95% CI = 1.07 to 1.74, P < 0.001) and inversely correlated with BMI (WMD = − 1.35, 95% CI = -1.67 to − 1.03, P < 0.001) but not with age (WMD = -0.93, 95% CI = -2.19 to 0.33, P = 0.149) or weight (WMD = 0.24, 95% CI = -2.24 to 2.72, P = 0.850). The severity of varicocele was inversely correlated with increased BMI but not with age. Conclusion The presence of varicoceles was significantly associated with height and inversely correlated with BMI.

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