Cardiovascular outcomes with sodium–glucose cotransporter-2 inhibitors in patients with type II diabetes mellitus: A meta-analysis of placebo-controlled randomized trials

Saad, Marwan; Mahmoud, Ahmed; Elgendy, Islam Y.; Abu‐Zaid, Ahmed; Barakat, Amr F.; Al‐Ani, Mohammad; Mentias, Amgad; Nairooz, Ramez; Bavry, Anthony A.; Mukherjee, Debabrata

doi:10.1016/j.ijcard.2016.11.181

Cited by 62 publications

(38 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…When we searched PubMed for other relevant meta-analyses, we found 3 that analyzed cardiovascular outcomes of SGLT2 inhibitors. [31][32][33] In all cases, the prior meta-analyses were limited to RCTs, primarily to evaluate the glucose-lowering effects of SGLT2 inhibitors (except the EMPA-REG OUTCOME trial) but not the cardiovascular safety outcomes. In these trials, cardiovascular outcomes were not predefined and independently adjudicated, and thus detection bias was not negligible.…”

Section: Comparisons With Other Meta-analysesmentioning

confidence: 99%

Cardiovascular Safety, Long‐Term Noncardiovascular Safety, and Efficacy of Sodium–Glucose Cotransporter 2 Inhibitors in Patients With Type 2 Diabetes Mellitus: A Systemic Review and Meta‐Analysis With Trial Sequential Analysis

Zhang

Zhu

Chen

et al. 2018

JAHA

108

View full text Add to dashboard Cite

BackgroundThe cardiovascular and long‐term noncardiovascular safety and efficacy of SGLT2 (sodium–glucose cotransporter 2) inhibitors have not been well documented.Methods and ResultsFor cardiovascular outcomes, we performed a meta‐analysis with trial sequential analysis of randomized controlled trials and adjusted observational studies, each with a minimum of 26 weeks and 2000 patient‐years of follow‐up. For long‐term noncardiovascular safety and efficacy outcome analyses, we included only randomized controlled trials with at least 2 years and 1000 patient‐years of follow‐up. Five studies with 351 476 patients were included in cardiovascular outcomes analysis. Meta‐analyses showed that SGLT2 inhibitors significantly reduced the risks of major adverse cardiac events (hazard ratio [HR]: 0.80; 95% confidence interval [CI], 0.69–0.92; P=0.002), all‐cause mortality (HR: 0.67; 95% CI, 0.54–0.84; P<0.001), cardiovascular mortality (HR: 0.77; 95% CI, 0.60–0.98; P=0.03), nonfatal myocardial infarction (HR: 0.86; 95% CI, 0.76–0.98; P=0.02), hospitalization for heart failure (HR: 0.62; 95% CI, 0.55–0.69; P<0.001), and progression of albuminuria (HR: 0.68; 95% CI, 0.58–0.81; P<0.001). No significant difference in nonfatal stroke was found. Analyses limited to randomized controlled trials showed similar findings. Trial sequential analysis provided firm evidence of a 20% reduction in major adverse cardiac events, all‐cause mortality, and hospitalization for heart failure with SGLT2 inhibitors, but evidence remains inconclusive for cardiovascular mortality. Nine randomized controlled trials contributed to long‐term noncardiovascular and efficacy analyses. SGLT2 inhibitors reduced incidence of hypoglycemia and acute kidney injury but increased the risks of urinary tract and genital infections.Conclusions SGLT2 inhibitors showed remarkable cardiovascular‐ and renal‐protective effects and good long‐term noncardiovascular safety with sustained efficacy.

show abstract

Section: Comparisons With Other Meta-analysesmentioning

confidence: 99%

Cardiovascular Safety, Long‐Term Noncardiovascular Safety, and Efficacy of Sodium–Glucose Cotransporter 2 Inhibitors in Patients With Type 2 Diabetes Mellitus: A Systemic Review and Meta‐Analysis With Trial Sequential Analysis

Zhang

Zhu

Chen

et al. 2018

JAHA

108

View full text Add to dashboard Cite

show abstract

“…A detailed explanation of the methods was discussed in a prior publication [4]. A comprehensive search of the MEDLINE, CENTRAL, Web of Science, Embase and Clinialtrials.gov databases was conducted without language restrictions from inception until July 2016 for randomized trials that compared SGLT-2 inhibitors with placebo in patients with type 2 diabetes, and reported cardiovascular outcomes.…”

Section: Methodsmentioning

confidence: 99%

Does Gender Influence the Cardiovascular Benefits Observed with Sodium Glucose Co-Transporter-2 (SGLT-2) Inhibitors? A Meta-Regression Analysis

et al. 2016

Self Cite

View full text Add to dashboard Cite

IntroductionAlthough a large recent trial had shown improved cardiovascular outcomes of diabetic patients on sodium glucose co-transporter-2 (SGLT-2) inhibitors, the influence of gender differences on such outcomes is not known. Thus, we aimed to assess the impact of gender on such outcomes in the patients with type 2 diabetes mellitus receiving SGLT-2 inhibitors.MethodsA search of electronic databases was conducted for all randomized trials comparing SGLT-2 inhibitors with placebo in patients with diabetes mellitus. Primary outcomes were all-cause mortality and cardiovascular mortality. Random effects meta-regression was conducted using the percentage of women included in the SGLT-2 inhibitor arm of each trial with a P value of <0.1 for statistical significance.ResultsA total of 22,256 patients from 26 trials were included. The overall odds ratio (OR) of all-cause mortality [OR = 0.72, 95% confidence interval (CI) 0.60–0.86, P < 0.001, I 2 = 0%], and cardiovascular mortality (OR = 0.67, 95% CI 0.53–0.84, P = 0.001, I 2 = 23%) were lower with SGLT-2 inhibitors. Meta-regression suggested a possible incremental increase in the OR for all-cause mortality and cardiovascular mortality as the percentage of women in the SGLT-2 inhibitor arm increased (P = 0.07 and 0.08, respectively).ConclusionGender might influence the cardiovascular benefits observed with SGLT-2 inhibitors in patients with type 2 diabetes mellitus.Electronic supplementary materialThe online version of this article (doi:10.1007/s40119-016-0075-1) contains supplementary material, which is available to authorized users.

show abstract

“…The reduction in all-cause mortality was noticed with empagliflozin but not with other SGLT2 inhibitors. 77 A potential harm was observed with dapagliflozin on CV mortality (OR 2.15; 95% CI, 0.92-5.04; P ¼ .08). 77…”

Section: S24mentioning

confidence: 99%

Cardiovascular Protection in the Treatment of Type 2 Diabetes: A Review of Clinical Trial Results Across Drug Classes

Paneni

Lüscher

2017

The American Journal of Cardiology

View full text Add to dashboard Cite

Patients with type 2 diabetes (T2DM) have a significantly higher risk of developing cardiovascular disease (CVD)-namely myocardial infarction, heart failure, and stroke. Despite clear advances in the prevention and treatment of CVD, the impact of T2DM on CVD outcome remains high and continues to escalate. Available evidence indicates that the risk of macrovascular complications increases with the severity of hyperglycemia, thus suggesting that the relation between metabolic disturbances and vascular damage is approximately linear. Although current antidiabetic drugs are highly effective for the management of hyperglycemia, most T2DM patients remain exposed to a substantial and concrete risk of CVD. Over the last decade many glucose-lowering agents have been tested for their safety and efficacy in T2DM with CVD. Noteworthy, most of these studies failed to show a significant benefit in terms of CV morbidity and mortality, despite intensive glycemic control. The recent trials Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUTCOME); Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes (SUSTAIN-6); Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER); and Insulin Resistance Intervention After Stroke (IRIS) have shed some light on this important clinical issue, thus showing a convincing effect of empagliflozin, liraglutide, and pioglitazone on CVD outcomes. Here we provide a critical and updated overview of the main glucose-lowering agents and their risk/benefit ratio for the prevention of CVD in patients with T2DM.

show abstract

Cardiovascular outcomes with sodium–glucose cotransporter-2 inhibitors in patients with type II diabetes mellitus: A meta-analysis of placebo-controlled randomized trials

Cited by 62 publications

References 32 publications

Cardiovascular Safety, Long‐Term Noncardiovascular Safety, and Efficacy of Sodium–Glucose Cotransporter 2 Inhibitors in Patients With Type 2 Diabetes Mellitus: A Systemic Review and Meta‐Analysis With Trial Sequential Analysis

Cardiovascular Safety, Long‐Term Noncardiovascular Safety, and Efficacy of Sodium–Glucose Cotransporter 2 Inhibitors in Patients With Type 2 Diabetes Mellitus: A Systemic Review and Meta‐Analysis With Trial Sequential Analysis

Does Gender Influence the Cardiovascular Benefits Observed with Sodium Glucose Co-Transporter-2 (SGLT-2) Inhibitors? A Meta-Regression Analysis

Cardiovascular Protection in the Treatment of Type 2 Diabetes: A Review of Clinical Trial Results Across Drug Classes

Contact Info

Product

Resources

About