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    Home > Active Ingredient News > Endocrine System > Diabetes Obes Metab: Effects of Exenatide and Dapagliflozin Monotherapy or Combination Therapy on Renal Function Markers in Obesity Patients with Type 2 Diabetes twice a day

    Diabetes Obes Metab: Effects of Exenatide and Dapagliflozin Monotherapy or Combination Therapy on Renal Function Markers in Obesity Patients with Type 2 Diabetes twice a day

    • Last Update: 2021-11-11
    • Source: Internet
    • Author: User
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    Purpose: Sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RAs) are used to improve blood sugar control, induce weight loss, and lower blood pressure in patients with type 2 diabetes.
    Sugar medicine

    .
    In addition, SGLT2 inhibitors have been specifically studied to prove that they can
    reduce the risk of renal failure in patients with chronic kidney disease
    .
    The secondary analysis of cardiovascular outcome trials in patients with type 2 diabetes showed that
    GLP-1RAs can also delay the progression of decreased renal function in patients with type 2 diabetes
    .
    The purpose of this study is to evaluate the sodium-glucose cotransporter-2 (SGLT2) inhibitor dadagliflozin and the glucagon-like peptide-1 receptor agonist (GLP-1RA) exenatide single agent and combination The effect of application on renal function

    .

    Hypoglycemic drugs that improve blood sugar control, induce weight loss, and lower blood pressure in patients with type 2 diabetes reduce the risk of renal failure in patients with chronic kidney disease GLP-1RAs can also delay the progression of decreased renal function in patients with type 2 diabetes

    Methods: In the secondary analysis of the weight reduction trial, we recruited 66 obese patients with type 2 diabetes for a 16-week randomized, double-blind, placebo-controlled clinical trial.
    And a clinical follow-up will be carried out after 16 weeks

    .
    Participants collected 24-hour urine samples after baseline, 1.
    5-week, and 16-week follow-ups

    .
    At these time points, blood samples were also collected to assess clinical chemistry variables

    .
    After the baseline measurement, an independent experimental pharmacist used computer-generated numbers to randomly divide the participants into 1:1:1:1 blocks to randomly assign the participants to: dapagliflozin 10mg once a day, placebo Exenatide 2 times a day; Exenatide 10 μg/day, placebo dapagliflozin; Dapagliflozin 10 mg, once a day; Exenatide 10 μg, twice a day; or placebo Dapagliflozin and placebo exenatide

    .
    The starting dose of Exenatide (or matching placebo) was 5 μg twice a day, and the dose was increased to 10 μg within 4 weeks, which was maintained until the end of the study

    .
    During the 16-week treatment period, instruct participants to inject exenatide (or placebo) 15-30 minutes before breakfast and dinner, and take dapagliflozin (or matching placebo) at 8:00 in the evening

    .
    Follow up compliance by counting remaining capsules and injection pens

    .
    All study drugs were provided by AstraZeneca

    .
    In order to keep the participants and researchers double-blind throughout the study, the participants received two injections and one tablet per day in a double-blind design

    .
    There is no difference in appearance between exenatide and placebo injections or dapagliflozin or placebo capsules

    .
    The main result of this study is the change in urine albumin:creatinine ratio (UACR) from baseline to week 16, assessed by 24-hour urine collection

    .
    Other endpoints include estimated glomerular filtration rate (calculated by the [CKD-EPI] formula and the CKD-EPI Cystatin C equation to calculate serum creatinine), urine kidney injury molecule-1 (KIM-1) and creatinine ratio (KIM -1: Cr) and changes in systolic blood pressure

    .

    Results: At week 16, compared with baseline, the average change in UACR in the exenatide group was 39.
    6% (95% CI 58.
    6, 11.
    9, P=0.
    001), and the average change in UACR in the dapagliflozin group was 18.
    1% ( 95% CI 43.
    1, 18.
    0, P=0.
    278), the average change in UACR in the exenatide group was 15.
    6% (95% CI 41.
    4, 21.
    6, P=0.
    357), and the average change in UACR in the placebo group was 11.
    0% (95% CI 39.
    8, 31.
    5, P=0.
    552)

    .
    Compared with placebo, the difference in UACR at week 16 in the exenatide-dapagliflozin group was 32.
    2% (95% CI 60.
    7, 16.
    9; P=0.
    159)

    .
    The effect was similar among 37 participants who used angiotensin-converting enzyme inhibitors or angiotensin receptor blockers at baseline

    .
    Compared with placebo, the glomerular filtration rate of the exenatide-dapagliflozin group dropped sharply (the estimated glomerular filtration rate of creatinine was -4.
    0mL/min/1.
    73m
    2 [95%CI- 9.
    3, 1.
    2]; P=0.
    129) and cystatin C estimated glomerular filtration rate (-10.
    4mL/min/1.
    73m
    2 [95%CI-14.
    9,-5.
    8]; P<0.
    001)

    .
    The average KIM-1:Cr difference between the combination treatment group and the placebo group was -43.
    8% (95%CI-73.
    5, 18.
    9; P=0.
    129)

    .

    2 2

    Table Baseline characteristics of subjects

    Table Baseline characteristics of subjects

    Figure taking placebo (red, n=14), exenatide (grey, n=16), dapagliflozin (light blue, n=16) and exenatide-dapagliflozin (dark blue) , N=16) Changes in renal function after 16 weeks
    .
    A, changes in urine albumin: creatinine ratio (UACR;%)

    .
    B, The change of urinary albumin excretion in 24 hours (%)

    .
    C, Changes in UACR of 37 participants (placebo, n=10; exenatide n = 12; dapagliflozin, n = 5; exenatide-dapagliflozin, n=10), use Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers

    .
    D, Change in urine kidney injury molecule-1:creatinine ratio (%)

    .
    E, the change in the estimated glomerular filtration rate of creatinine (eGFRcreat; mL / min / 1.
    73 square meters)

    .
    F, estimated GFR of cystatin c (eGFRcystC; mL / min / 1.
    73 square meters)

    .
    CI, confidence interval; KIM, kidney injury molecule-1

    Figure taking placebo (red, n=14), exenatide (grey, n=16), dapagliflozin (light blue, n=16) and exenatide-dapagliflozin (dark blue) , N=16) Changes in renal function after 16 weeks
    .
    A, changes in urine albumin: creatinine ratio (UACR;%)

    .
    B, The change of urinary albumin excretion in 24 hours (%)

    .
    C, Changes in UACR of 37 participants (placebo, n=10; exenatide n = 12; dapagliflozin, n = 5; exenatide-dapagliflozin, n=10), use Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers

    .
    D, Change in urine kidney injury molecule-1:creatinine ratio (%)

    .
    E, the change in the estimated glomerular filtration rate of creatinine (eGFRcreat; mL / min / 1.
    73 square meters)

    .
    F, estimated GFR of cystatin c (eGFRcystC; mL / min / 1.
    73 square meters)

    .
    CI, confidence interval; KIM, kidney injury molecule-1

    Conclusion: This study shows that the combination of dapagliflozin and exenatide may have a synergistic effect on renal function indicators in obese patients with type 2 diabetes compared with monotherapy or placebo
    .

    This study shows that, compared with monotherapy or placebo, the combination of dapagliflozin and exenatide may have a synergistic effect on renal function indicators in obese patients with type 2 diabetes
    .

    Original source:

    van Ruiten CC, van der Aart-van der Beek AB, IJzerman RG,et al.
    Effect of exenatide twice daily and dapagliflozin, alone and in combination, on markers of kidney function in obese patients with type 2 diabetes: A prespecified secondary analysis of a randomized controlled clinical trial .
    Diabetes Obes Metab 2021 Aug;23(8)

    Effect of exenatide twice daily and dapagliflozin, alone and in combination, on markers of kidney function in obese patients with type 2 diabetes: A prespecified secondary analysis of a randomized controlled clinical trial

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