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    Home > Active Ingredient News > Endocrine System > Qiu Fuyu: From mechanism to evidence-based, let's take a look at how new hypoglycemic drugs can protect the heart and kidney

    Qiu Fuyu: From mechanism to evidence-based, let's take a look at how new hypoglycemic drugs can protect the heart and kidney

    • Last Update: 2021-06-05
    • Source: Internet
    • Author: User
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    In recent years, more and more studies have shown that new hypoglycemic drugs can not only lower blood sugar, but also protect the heart and kidneys of non-diabetic patients.

    So what are the effects of these drugs on the heart and kidneys of non-diabetic patients? What is the particularity of its mechanism? Let's take a look at what the experts say about it! On May 29, 2021, Professor Qiu Fuyu of Zhejiang University gave a lecture on appeal issues at the 15th Oriental Cardiology Conference (OCC2021).

    This article summarizes the relevant introduction, while referring to the effects of hypoglycemic drugs on the cardiovascular system, it focuses on introducing the renal benefits and related mechanisms of hypoglycemic drugs.

     Diabetes-lowering drugs open heart and kidney benefits.
    A new cross-border exploration.
    Professor Qiu introduced that the research of traditional hypoglycemic drugs is mainly focused on diabetic patients, and there are contradictions.

    In summary, some traditional hypoglycemic drugs can have an impact on the cardiovascular and kidneys of patients with type 2 diabetes, as shown in the figure below (Figure 1).

    Figure 1 The effect of traditional hypoglycemic drugs on cardiovascular and kidney in patients with type 2 diabetes.
    Source: Professor Qiu Fuyu's lecture on OCC2021.
    Among the new hypoglycemic drugs, sodium-glucose cotransporter 2 inhibitors (SGLT-2 inhibitors) are A very representative drug, which has a good protective effect on the cardiovascular and kidneys.

    Therefore, Professor Qiu focused on the cardiorenal benefits of SGLT-2 inhibitors for non-diabetic patients.

    Exploration of SGLT-2 Inhibitors in Cardiovascular Diseases Without Diabetes.
    The 2019ESC released the results of the DAPA-HF study.
    The primary endpoint showed that dapagliflozin can significantly reduce the risk of cardiovascular death or heart failure worsening by 26%, and significantly reduce the risk of heart failure.
    The risk of vascular death was 18%, and the risk of worsening heart failure was significantly reduced by 30%.

    As for the secondary endpoint, dapagliflozin can significantly reduce the risk of all-cause death in patients with heart failure by 17%, and significantly improve the KCCQ score of patients with an improvement rate of 15%.

     In addition, studies have shown that in non-diabetic people with heart failure, the ratio of doubling the serum creatinine of dapagliflozin tends to decrease.

     In terms of safety, the interruption rate of dapagliflozin treatment is low, and the main hypoglycemia time of non-diabetic population is zero.

     Enpagliflozin can significantly reduce cardiovascular death or hospitalization for heart failure by 25% in patients with chronic ejection fraction reduction and heart failure with or without type 2 diabetes, and significantly reduce the risk of renal composite endpoints (dialysis, Renal transplantation or glomerular filtration rate is significantly reduced) up to 50%.

    A total of 3730 patients were enrolled, and 50.
    2% of patients were not accompanied by type 2 diabetes.

     Expert consensus and heart failure guidelines have slowed down.
    In the 2021 ACC expert consensus, SGLT-2 inhibitors have been included in the first-line treatment for patients with heart failure that reduce ejection fraction.

    Both domestic and foreign heart failure guidelines list SGLT-2 inhibitors in the standard treatment of heart failure.
    These guidelines include the diagnosis and treatment guidelines for primary treatment of chronic heart failure (2019), the Canadian Heart Association/Canadian Heart Failure Association Heart Failure Guidelines (2020) and the primary care Guidelines for Comprehensive Management of Cardiovascular Diseases (2020).

     Exploration of SGLT-2 Inhibitors in Kidney Diseases Without DiabetesProfessor Qiu introduced that in the dapagliflozin prevention of adverse outcomes in chronic kidney disease (DAPA-CKD) study, the result of the primary endpoint was a significant reduction in the primary composite endpoint ( eGFR continued to decrease ≥50%, end-stage renal disease, death due to nephropathy or cardiovascular events) reached 39%.

    In terms of secondary endpoints, the renal-specific endpoints (eGFR continued to decrease ≥50%, end-stage renal disease, or death due to renal disease) were significantly reduced by 44%, and the composite endpoint of cardiovascular death or heart failure hospitalization was significantly reduced by 29%.
    The risk of death from all causes is 31%.

    Other information of DAPA-CKD research is shown in the figure below (Figure 2).

    Figure 2 Other sources of information for the DAPA-CKD study: Professor Qiu Fuyu’s lecture on OCC2021 For CKD patients without diabetes, dapagliflozin can significantly reduce the risk of cardiorenal end-point events.
    For the vascular composite endpoint and all-cause mortality, the hazard ratio was 0.
    50 (95% CI, 0.
    35-0.
    72; P=0.
    24); for the kidney-specific endpoint, the hazard ratio was 0.
    51 (95% CI, 0.
    34-0.
    75; P= 0.
    57); for the cardiovascular composite endpoint, the hazard ratio was 0.
    79 (95% CI, 0.
    40-1.
    55; P=0.
    78); for all-cause mortality, the hazard ratio was 0.
    52 (95% CI, 0.
    29-0.
    93; P=0.
    25) .

    In terms of safety, there was no significant difference between the dapagliflozin group and the placebo group.

     Professor Qiu made it clear that the KDIGO clinical guidelines: recommend SGLT-2 inhibitors (1A) and metformin (1B) as first-line treatments for patients with diabetes and CKD.
    The specific recommendations are shown in the figure below (Figure 3).

    Figure 3 KDIGO's recommended content source for SGLT-2 inhibitors: Professor Qiu Fuyu's lecture at OCC2021 Professor Qiu believes that as more and more trials focus on patients with non-type 2 diabetes, more SGLT-2 inhibitors will be available in the future Used in non-diabetic patients, for these people, the heart and kidney will get certain benefits.

    Exploring the potential mechanism of SGLT-2 inhibitors' new kidney benefits Professor Qiu introduced that SGLT-2 inhibitors have a unique sugar-exhausting mechanism that can improve energy and hemodynamics.

    SGLT-2 inhibitors inhibit the renal tubular sodium-glucose cotransporter, lower the renal glucose valve, reduce the reabsorption of glucose in the urine, and thereby reduce the level of glucose.

    In this case, the extra urine output per day can be increased by 300-400ml.

    The potential mechanism of SGLT-2 inhibitors to improve the outcome of heart failure is shown in the figure below (Figure 4).

    Figure 4 The potential mechanism of SGLT-2 inhibitors to improve the resolution of heart failure.
    Source: Professor Qiu Fuyu's lecture on OCC2021.
    In terms of renal resolution, the pharmacological properties of SGLT-2 inhibitors can improve renal outcome.

    SGLT-2 inhibitors can reduce glomerular pressure, improve neurohormones, reduce inflammation and fibrosis, reduce kidney workload and hypoxia, and achieve the following clinical effects, such as eGFR stabilization, decreased blood pressure, renal tubules and glomeruli Decreased damage, decreased albuminuria, decreased renal ischemic damage, and increased hemoglobin or hematocrit.

    It will ultimately help preserve kidney function.
    Please see the figure below for the specific process (Figure 5).

    Figure 5 Sources of potential effects of SGLT-2 inhibitors in improving renal outcomes: Professor Qiu Fuyu’s lecture on OCC2021 Explores the new kidney benefits of other hypoglycemic drugs Professor Qiu introduced that GLP-1 receptor agonists have not yet been explored for their benefits Clinical studies on improving the heart and kidney function of non-diabetic patients, but some studies have found that GLP-1 receptor agonists can effectively reduce weight and improve cardiometabolic risk factors.

    Simeglutide can improve the 10-year risk of atherosclerotic cardiovascular disease in overweight or obese patients, and the continuous use of smeglutide 2.
    4mg can continuously improve cardiometabolic risk factors.

    In the future, there may be more experimental results supporting the protective effect of GLP-1 receptor agonists on the heart and kidney of non-diabetic patients.

     Finally, Professor Qiu summarized as follows: Conclusion ➤Traditional hypoglycemic drugs have limited cardiovascular and renal benefits.
    After the rosiglitazone event, new hypoglycemic drugs start from the cardiovascular outcome research, and SGLT-2 inhibitors gradually open the heart and kidney New exploration of cross-border benefits; ➤Dapagliflozin and Enpagliflozin have sufficient research evidence for the reduction of ejection fraction of non-diabetic patients with heart failure, and SGLT-2 inhibitors have been included as the first-line treatment for patients with heart failure with reduced ejection fraction Drugs; ➤DAPA-CKD research suggests that dapagliflozin significantly reduces the risk of cardiorenal end-point events in non-diabetic CKD patients, which provides more possibilities for the treatment of CKD patients; ➤SGLT-2 inhibitor's unique glycogen excretion mechanism, initiation To reduce the reabsorption of glucose and sodium ions in the proximal convoluted tubules, the follow-up effect acts on the whole body, bringing cardiorenal protection; ➤We look forward to more researches in the future to provide experimental data support for the cardiorenal protection of hypoglycemic drugs in non-diabetic patients.

    Professor Qiu Fuyu is the director of the Department of Cardiology at the Run Run Run Run Shaw Hospital of Zhejiang University School of Medicine.
    He gave a lecture on the theme of "Heart and Kidney Benefits of Hypoglycemic Drug Therapy for Non-diabetics" at the 15th Oriental Cardiology Conference.

    This article is organized according to the lecture content to form the above content.


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