Glucose-lowering drugs or strategies, atherosclerotic cardiovascular events, and heart failure in people with or at risk of type 2 diabetes: an updated systematic review and meta-analysis of randomized cardiovascular outcome trials

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    Original version

    Olivia R Ghosh-Swaby 1, Shaun G Goodman 2, Lawrence A Leiter 3, Alice Cheng 4, Kim A Connelly 5, David Fitchett 3, Peter J√ľni 6, Michael E Farkouh 7, Jacob A Udell 8

    Main idea: Glucose-lowering drugs or strategies overall reduced the risk of fatal and non-fatal atherosclerotic events. The effect on heart failure was neutral overall but varied substantially by intervention type, with interventions associated with weight loss showing a beneficial effect. The cardiovascular and heart failure benefits of interventions associated with weight loss might extend to patients without established cardiovascular disease.

    Abstract

    Background: In our 2015 systematic review and meta-analysis of cardiovascular outcome trials for glucose-lowering drugs or strategies in people with or at risk of type 2 diabetes, we reported a modest reduction in atherosclerotic cardiovascular events and an increased risk of heart failure, but with heterogeneous effects by drug or intervention type. In view of the completion of many large cardiovascular outcome trials since our previous analysis, including trials of novel drugs that have shown beneficial effects on cardiovascular outcomes, we aimed to update our analysis to incorporate these findings.

    Methods: We searched Ovid MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials databases for reports of trials published from Nov 15, 2013 to Nov 20, 2019. We included randomised controlled trials with a minimum of 1000 adults with or at risk of type 2 diabetes, with major adverse cardiovascular events (MACE) as an outcome. The main outcomes of interest were MACE (generally defined as a composite of cardiovascular death, myocardial infarction, or stroke) and heart failure. Findings: Glucose-lowering drugs or strategies lowered the risk of MACE compared with standard care or placebo. However, across drug classes or strategies, the magnitude and directionality of RR for heart failure varied. Meta-regression showed that a decrease in bodyweight of 1 kg was associated with a 5.9% relative decrease in risk of heart failure. Among trials that assessed weight loss, intensive lifestyle changes, GLP-1 receptor agonists, or SGLT2 inhibitors had no effect on heart failure risk in those who lost weight (pinteraction=0 63)

    Medium version

    Main idea: Drugs or strategies that lower blood glucose levels have overall reduced the risk of fatal and non-fatal atherosclerotic events. The effect on heart failure was neutral overall. Still, it varied substantially, with interventions associated with weight loss showing a beneficial effect. The cardiovascular and heart failure benefits of treatments related to weight loss might extend to patients without established cardiovascular disease.

    Abstract

    In 2015, there was a systematic review and meta-analysis of cardiovascular outcome trials for glucose-lowering drugs or strategies in people with or at risk of type 2 diabetes. It showed a modest reduction in atherosclerotic cardiovascular events and an increased risk of heart failure. Still, there was a variety in effects depending on drug or intervention type. Since then, many large cardiovascular outcome trials have been completed, including trials of novel drugs that have shown beneficial effects on cardiovascular outcomes. Therefore, this work aimed to update the research to incorporate these findings.

    The research group investigated Ovid MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials databases for reports of trials published from Nov 15, 2013, to Nov 20, 2019. They included randomized controlled trials with a minimum of 1000 adults with or at risk of type 2 diabetes. The primary outcomes of interest were heart failure and major adverse cardiovascular events (MACE), generally defined as a composite of cardiovascular death, myocardial infarction, or stroke.

    Glucose-lowering drugs or strategies reduced the risk of MACE compared with standard care or placebo. However, the magnitude and directionality of the risk ratio for heart failure varied across drug classes or strategies. It was also shown that a decrease in body weight of 1 kg was associated with a 5.9% relative decrease in risk of heart failure. Among trials that assessed weight loss, intensive lifestyle changes, GLP-1 receptor agonists, or SGLT2 inhibitors had no effect on heart failure risk in those who lost weight.

    Easy version

    Main idea: Drugs or strategies that lower blood sugar levels have overall reduced the risk of problems associated with arteries hardening and narrowing. The effect on heart failure was neutral overall. But interventions related to weight loss showed a beneficial effect.

    Abstract

    Previously, there was a systematic review and meta-analysis of the blood sugar-lowering drugs effects on the cardiovascular system in people with or at risk of type 2 diabetes. It showed a modest reduction in problems associated with arteries hardening and an increased risk of heart failure. Since then, many other trials have been completed, including novel drugs that have shown beneficial effects on cardiovascular outcomes.
    In the current study, the research group investigated databases for reports of trials published from Nov 15, 2013, to Nov 20, 2019. They included randomized controlled trials with a minimum of 1000 adults with or at risk of type 2 diabetes. The primary outcomes of interest were heart failure and major adverse cardiovascular events (MACE).

    Based on the research, drugs or strategies for lowering blood sugar levels reduced the risk of MACE compared with standard care or placebo. It was also shown that a decrease in body weight of 1 kg was associated with a 5.9% relative decrease in risk of heart failure.

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