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    Home > Active Ingredient News > Endocrine System > Cardiovasc Diabetol: Mechanisms of antihypertensive effects of dapagliflozin, exenatide and their combination in patients with type 2 diabetes

    Cardiovasc Diabetol: Mechanisms of antihypertensive effects of dapagliflozin, exenatide and their combination in patients with type 2 diabetes

    • Last Update: 2022-05-15
    • Source: Internet
    • Author: User
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    Background: Type 2 diabetes (T2D) is associated with cardiovascular disease (CV) morbidity and mortality due to the combined effects of hyperglycemia and frequently associated obesity, dyslipidemia and hypertension
    .
    In the past few decades, two new classes of drugs have been developed to reduce multiple cardiovascular risk factors: inhibitors of sodium-glucose co-transporter 2 (SGLT2i) and glucagon-like peptide-1 receptor agonists agents (GLP-1RAs)

    .
    SGLT2i improved cardiovascular outcomes (3-MACE), especially heart failure (hospitalization), and improved mortality in patients with atherosclerotic disease, regardless of the presence of diabetes, suggesting that the cardiovascular benefit goes beyond glucose lowering
    .
    Reduction in blood pressure (BP) may contribute to improved cardiovascular outcomes to some extent
    .
    The hypotensive effect of SLGT2i is approximately 4 mm Hg

    .
    The underlying mechanism of the blood pressure-lowering effect is still not fully understood, but persistently reduced plasma volume may play a role

    .
    Since reductions in plasma volume and (arterial) blood pressure do not increase heart rate (HR), it has been suggested that sympathetic nervous system (SNS) activity will also decrease

    .
    Improvements in arterial stiffness and endothelial function are also thought to contribute to long-term lowering of blood pressure
    .

    Background: Type 2 diabetes (T2D) is associated with cardiovascular disease (CV) morbidity and mortality due to the combined effects of hyperglycemia and frequently associated obesity, dyslipidemia and hypertension
    .
    In the past few decades, two new classes of drugs have been developed to reduce multiple cardiovascular risk factors: inhibitors of sodium-glucose co-transporter 2 (SGLT2i) and glucagon-like peptide-1 receptor agonists agents (GLP-1RAs)

    .
    SGLT2i improved cardiovascular outcomes (3-MACE), especially heart failure (hospitalization), and improved mortality in patients with atherosclerotic disease, regardless of the presence of diabetes, suggesting that the cardiovascular benefit goes beyond glucose lowering
    .
    Reduction in blood pressure (BP) may contribute to improved cardiovascular outcomes to some extent
    .
    The hypotensive effect of SLGT2i is approximately 4 mm Hg

    .
    The mechanisms underlying the blood pressure-lowering effect are still not fully understood, but persistently reduced plasma volume may play a role

    .
    Since reductions in plasma volume and (arterial) blood pressure do not increase heart rate (HR), it has been suggested that sympathetic nervous system (SNS) activity will also decrease

    .
    Improvements in arterial stiffness and endothelial function are also thought to contribute to long-term lowering of blood pressure
    .
    Type 2 diabetes (T2D) is associated with cardiovascular disease (CV) morbidity and mortality due to the combined effects of hyperglycemia and frequently associated obesity, dyslipidemia and hypertension
    .
    In the past few decades, two new classes of drugs have been developed to reduce multiple cardiovascular risk factors: inhibitors of sodium-glucose co-transporter 2 (SGLT2i) and glucagon-like peptide-1 receptor agonists agents (GLP-1RAs)

    .
    Reduction in blood pressure (BP) may contribute to improved cardiovascular outcomes to some extent
    .
    The hypotensive effect of SLGT2i is approximately 4 mm Hg

    .
    The underlying mechanism of the blood pressure lowering effect is not fully understood, but persistently reduced plasma volume may play a role

    .
    Since reductions in plasma volume and (arterial) blood pressure do not increase heart rate (HR), it has been suggested that sympathetic nervous system (SNS) activity will also decrease

    .

    Similar to SGLT2i, GLP-1RAs reduce cardiovascular disease (CVD) in patients with T2D, and the mode of action is not fully understood but may be multifactorial
    .
    GLP-1RAs lower blood pressure (the magnitude of the reduction depends on the drug used), which may help reduce cardiovascular disease

    .
    Mechanisms of the hypotensive effect of GLP-1-RA may include decreased vascular resistance, sodium excretion, and weight loss

    .

    Similar to SGLT2i, GLP-1RAs reduce cardiovascular disease (CVD) in patients with T2D, and the mode of action is not fully understood but may be multifactorial
    .
    GLP-1RAs lower blood pressure (the magnitude of the reduction depends on the drug used), which may help reduce cardiovascular disease

    .
    Mechanisms of the hypotensive effect of GLP-1-RA may include decreased vascular resistance, sodium excretion, and weight loss

    .

    OBJECTIVE: The aim of this study was to evaluate the mechanism by which SGLT2i dapagliflozin, GLP-1RA exenatide and dapagliflozin-exenatide lower blood pressure compared with placebo in obese and type 2 diabetic patients
    .

    OBJECTIVE: The aim of this study was to evaluate the mechanism by which SGLT2i dapagliflozin, GLP-1RA exenatide and dapagliflozin-exenatide lower blood pressure compared with placebo in obese and type 2 diabetic patients
    .

    METHODS: Sixty-six patients with type 2 diabetes were randomized to receive dapagliflozin 10 mg/d, exenatide 10 µg/d, dapagliflozin-exenatide or placebo for 16 weeks
    .
    After 10 days and 16 weeks of treatment, the effect of treatment on the following indicators was assessed: (1) plasma volume (calculated by Strauss formula), bioimpedance spectrum, hematocrit, (2) autonomic nervous system activity (heart rate variability), (3) arterial stiffness (pulse wave applanation), (4) systemic hemodynamic parameters (including peripheral vascular resistance, cardiac output, and stroke volume) (all from non-invasive systemic hemodynamic monitoring), (5) Natriuria (24-hour urine collection)

    .

    METHODS: Sixty-six patients with type 2 diabetes were randomized to receive dapagliflozin 10 mg/d, exenatide 10 µg/d, dapagliflozin-exenatide or placebo for 16 weeks
    .
    After 10 days and 16 weeks of treatment, the effect of treatment on the following indicators was assessed: (1) plasma volume (calculated by Strauss formula), bioimpedance spectrum, hematocrit, (2) autonomic nervous system activity (heart rate variability), (3) arterial stiffness (pulse wave applanation), (4) systemic hemodynamic parameters (including peripheral vascular resistance, cardiac output, and stroke volume) (all from non-invasive systemic hemodynamic monitoring), (5) Natriuria (24-hour urine collection)

    .

    Results: After 10 days of administration, dapagliflozin decreased blood pressure by 4.
    7 mm Hg, systolic blood pressure and plasma volume

    .
    After 16 weeks, dapagliflozin reduced blood pressure by 4.
    4 mmHg and decreased sympathetic nervous system activity

    .
    Exenatide had no effect on SBP but decreased parasympathetic nervous system activity after 10 days and 16 weeks of treatment

    .
    After 10 days of treatment, dapagliflozin-exenatide reduced blood pressure by 4.
    2 mm Hg and plasma volume

    .
    After 16 weeks of treatment, dapagliflozin-exenatide reduced blood pressure by 6.
    8 mm Hg, and plasma volume still decreased, but had no significant effect on SNS values

    .

    Results: After 10 days of administration, dapagliflozin decreased blood pressure by 4.
    7 mm Hg, systolic blood pressure and plasma volume

    .
    After 16 weeks, dapagliflozin reduced blood pressure by 4.
    4 mmHg and decreased sympathetic nervous system activity

    .
    Exenatide had no effect on SBP but decreased parasympathetic nervous system activity after 10 days and 16 weeks of treatment

    .
    After 10 days of treatment, dapagliflozin-exenatide reduced blood pressure by 4.
    2 mm Hg and plasma volume

    .
    After 16 weeks of treatment, dapagliflozin-exenatide reduced blood pressure by 6.
    8 mm Hg, and plasma volume still decreased, but had no significant effect on SNS values

    .

    Table 1 Changes in blood pressure and heart rate

    Table 1 Changes in blood pressure and heart rate

    Table 2 Cardiovascular function indicators

    Table 2 Cardiovascular function indicators

    Figure 1 Linear mixed models were used to compare the effects of baseline-corrected treatment and placebo
    .
    Changes in A and B autonomic balance after 10 days and 16 weeks of treatment with dapalizine (blue circle), exenatide (red square), and dapalizine plus exenatide (purple upper triangle)

    .
    Data points represent mean values ​​using scanning electron microscopy

    .
    After correction of the baseline value, the difference between the treatment group and the placebo group was statistically significant: *(P<0.
    001), **(P<0.
    01), *(P<0.
    05)

    .

    Figure 1 Linear mixed models were used to compare the effects of baseline-corrected treatment and placebo
    .
    Changes in A and B autonomic balance after 10 days and 16 weeks of treatment with dapalizine (blue circle), exenatide (red square), and dapalizine plus exenatide (purple upper triangle)

    .
    Data points represent mean values ​​using scanning electron microscopy

    .
    After correction of the baseline value, the difference between the treatment group and the placebo group was statistically significant: *(P<0.
    001), **(P<0.
    01), *(P<0.
    05)

    .

    Conclusion: Plasma volume contraction induced by dapagliflozin may be involved in the initial decrease in SBP, and the decrease in SNS activity may be one of the reasons for the persistent decrease in SBP
    .
    Dapagliflozin-Exenatide had the largest SBP reduction

    .
    The effect on plasma volume was comparable to that of dapagliflozin alone, and SNS activity was not reduced, so there may be other mechanisms contributing to the antihypertensive effect of this combination, which needs further study

    .

    Conclusion: Plasma volume contraction induced by dapagliflozin may be involved in the initial decrease in SBP, and the decrease in SNS activity may be one of the reasons for the persistent decrease in SBP
    .
    Dapagliflozin-Exenatide had the largest SBP reduction

    .
    The effect on plasma volume was comparable to that of dapagliflozin alone, and SNS activity was not reduced, so there may be other mechanisms contributing to the antihypertensive effect of this combination, which needs further study

    .
    Plasma volume contraction induced by dapagliflozin may be involved in the initial decrease in SBP, and the decrease in SNS activity may be one of the reasons for the persistent decrease in SBP
    .
    Dapagliflozin-Exenatide had the largest SBP reduction

    .
    The effect on plasma volume was comparable to that of dapagliflozin alone, and SNS activity was not reduced, so there may be other mechanisms contributing to the antihypertensive effect of this combination, which needs further study

    .

    Original source: van Ruiten CC, Smits MM, Kok MD, et al .
    Mechanisms underlying the blood pressure lowering effects of dapagliflozin, exenatide, and their combination in people with type 2 diabetes: a secondary analysis of a randomized trial
    .
    Cardiovasc Diabetol 2022 Apr 28;21(1)

    Original source: van Ruiten CC, Smits MM, Kok MD, et al .
    Mechanisms underlying the blood pressure lowering effects of dapagliflozin, exenatide, and their combination in people with type 2 diabetes: a secondary analysis of a randomized trial
    .
    Cardiovasc Diabetol 2022 Apr 28;21(1)
    .
    Mechanisms underlying the blood pressure lowering effects of dapagliflozin, exenatide, and their combination in people with type 2 diabetes: a secondary analysis of a randomized trial Leave a


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