scholarly journals Dapagliflozin : manfaat dan risiko pada diabetes melitus tipe 2

2019 ◽  
Vol 2 (2) ◽  
pp. 81-89
Author(s):  
Joice Viladelvia Kalumpiu
Keyword(s):  
Cardiovascular Events ◽  
Major Adverse Cardiovascular Events ◽  
Sodium Glucose Cotransporter ◽  
Cardiovascular Assessment ◽  
European Society Of Cardiology ◽  
Excess Glucose ◽  
Cardiology Guideline ◽  
Outcome Event ◽  
Diabetes Melitus

Dapagliflozin merupakan salah satu obat antidiabetes pemberian oral golongan penghambat sodium-glucose cotransporter-2 (SGLT2) yang digunakan pada penderita diabetes melitus tipe 2 (DMT2). Berbeda dengan antidiabetes oral lain yang bekerja menstimulasi sekresi insulin atau meningkatkan sensitivitas insulin, dapagliflozin bekerja di ginjal dengan cara menghambat secara kompetitif protein SGLT2 secara reversibel yang berperan dalam reabsorpsi glukosa di glomerulus sehingga menurunkan kadar gula dalam darah penderita DMT2. Beberapa studi telah dilakukan untuk melihat efek penghamabat SGLT2 dalam menurunkan kejadian kardiovaskular seperti Empagliflozin Cardiovascular Outcome Event Trial in Type-2 Diabetes Patients-Remove Excess Glucose, Canagliflozin Cardiovascular Assessment Study, dan studi multisenter yang mengevaluasi efek dapagliflozin pada insiden kejadian kardiovaskular yaitu Dapagliflozin Effect on Cardiovascular Events (DECLARE-TIMI 58) menunjukkan hasil yang kontradiksi. DECLARE-TIMI58 menunjukkan dapagliflozin tidak meningkatkan atau menurunkan risiko major adverse cardiovascular events (MACE) berbeda dengan obat golongan penghambat SGLT2 lainnya, namun studi ini menunjukkan dapagliflozin dapat menurunkan tingkat kematian dan rawat inap akibat penyakit gagal jantung.  The American College of Cardiology, the American Diabetes Association (ADA), dan The European Society of Cardiology guideline saat ini sudah merekomendasikan penggunaan penghambat SGLT2 (empagliflozin dan canagliflozin) sebagai obat tambahan pada pasien DMT2 dengan aterosklerosis. Hingga saat ini dapagliflozin belum direkomendasikan penggunaannya untuk penyakit kardiovaskular pencegahan aterosklerosis pada pasien DMT2 karena masih kurangnya studi-studi yang mendukung. Ketoasidosis  merupakan risiko yang perlu dipantau pada penggunaan obat penghambat SGLT2. Baru-baru ini FDA mengeluarkan adanya peringatan kejadian Fournier’s gangrene. Selain itu, peningkatan risiko fraktur dilaporkan pada penggunaan dapagliflozin dan perlu dipantau bila dimanfaatkan pada penderita DMT2 dalam praktik klinik.

scholarly journals Possible Sodium-Glucose Cotransporter-2 (SGLT-2) Inhibitors for Reducing Effects of Blood Glucose and also Blood Pressure

2020 ◽  
Vol 3 (3) ◽  
pp. 186-190
Author(s):  
Bando H
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Events ◽  
Hypoglycemic Agents ◽  
Outcome Study ◽  
Sodium Glucose Cotransporter ◽  
Target Values ◽  
Cardiovascular Assessment ◽  
Excess Glucose ◽  
Outcome Event

Sodium-glucose Cotransporter-2 Inhibitors (SGLT2i) has been in focus for the pharmacotherapy of diabetes. SGLT2i contributes to decreasing blood pressure (BP) to some degree. BP changes were analyzed in 4 well-known mega-studies. They are Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUTCOME) study, Canagliflozin cardioVascular Assessment Study (CANVAS), Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) and Dapagliflozin Effect on CardiovascuLAR Events (DECLARE)-TIMI 58. The ultimate goal of antihypertensive and hypoglycemic agents is not the achievement of target values, but the suppression of cardiovascular events. SGLT-2i show excellent strategy for event suppression and adjunct method for hypertension.

scholarly journals Clinical Influence of Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors for Cardiovascular and Renal Points of View

2020 ◽  
Vol 2 (S1) ◽  
pp. 9-13 ◽  
Author(s):  
Bando H
Keyword(s):  
Sglt2 Inhibitors ◽  
Outcome Study ◽  
Sodium Glucose Cotransporter ◽  
Cardiovascular Assessment ◽  
Points Of View ◽  
Long Term Prognosis ◽  
Excess Glucose ◽  
Outcome Event

Diabetes has been a major medical and health problem worldwide. Adequate glycemic control has shown a clinically beneficial effect for long-term prognosis, with recent anti-diabetic agents. There are some mega studies concerning Sodium-glucose cotransporter 2 (SGLT2) inhibitors. They are i) Canagliflozin cardioVascular Assessment Study (CANVAS), ii) Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE), iii) Dapagliflozin Effect on CardiovascuLAR Events (DECLARE) -TIMI 58, iv) Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUTCOME) study. Current topics of SGLT2 inhibitors for cardiovascular and renal points of view were described.

scholarly journals Early Change in Albuminuria with Canagliflozin Predicts Kidney and Cardiovascular Outcomes: A PostHoc Analysis from the CREDENCE Trial

2020 ◽  
Vol 31 (12) ◽  
pp. 2925-2936 ◽  
Author(s):  
Megumi Oshima ◽  
Brendon L. Neuen ◽  
JingWei Li ◽  
Vlado Perkovic ◽  
David M. Charytan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Cardiovascular Events ◽  
Renin Angiotensin System ◽  
Cardiovascular Death ◽  
Cardiovascular Outcomes ◽  
Major Adverse Cardiovascular Events ◽  
Early Change ◽  
Sodium Glucose Cotransporter

BackgroundThe association between early changes in albuminuria and kidney and cardiovascular events is primarily based on trials of renin-angiotensin system blockade. It is unclear whether this association occurs with sodium-glucose cotransporter 2 inhibition.MethodsThe Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial enrolled 4401 patients with type 2 diabetes and CKD (urinary albumin-creatinine ratio [UACR] >300 mg/g). This post hoc analysis assessed canagliflozin’s effect on albuminuria and how early change in albuminuria (baseline to week 26) is associated with the primary kidney outcome (ESKD, doubling of serum creatinine, or kidney death), major adverse cardiovascular events, and hospitalization for heart failure or cardiovascular death.ResultsComplete data for early change in albuminuria and other covariates were available for 3836 (87.2%) participants in the CREDENCE trial. Compared with placebo, canagliflozin lowered UACR by 31% (95% confidence interval [95% CI], 27% to 36%) at week 26, and significantly increased the likelihood of achieving a 30% reduction in UACR (odds ratio, 2.69; 95% CI, 2.35 to 3.07). Each 30% decrease in UACR over the first 26 weeks was independently associated with a lower hazard for the primary kidney outcome (hazard ratio [HR], 0.71; 95% CI, 0.67 to 0.76; P<0.001), major adverse cardiovascular events (HR, 0.92; 95% CI, 0.88 to 0.96; P<0.001), and hospitalization for heart failure or cardiovascular death (HR, 0.86; 95% CI, 0.81 to 0.90; P<0.001). Residual albuminuria levels at week 26 remained a strong independent risk factor for kidney and cardiovascular events, overall and in each treatment arm.ConclusionsIn people with type 2 diabetes and CKD, use of canagliflozin results in early, sustained reductions in albuminuria, which were independently associated with long-term kidney and cardiovascular outcomes.

Sodium–Glucose Cotransporter–2 (SGLT-2) Inhibitors and the Treatment of Type 2 Diabetes

2019 ◽  
Vol 70 (1) ◽  
pp. 323-334 ◽  
Author(s):  
Caroline K. Kramer ◽  
Bernard Zinman
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Cardiovascular Events ◽  
Acute Effect ◽  
Metabolic Effects ◽  
Major Adverse Cardiovascular Events ◽  
Cardiovascular Safety ◽  
Sodium Glucose Cotransporter

Clinical studies evaluating the cardiovascular safety/impact of sodium–glucose cotransporter–2 (SGLT-2) inhibitors demonstrated a reduction in major adverse cardiovascular events driven primarily by a reduced cardiovascular mortality in individuals with type 2 diabetes and previous cardiovascular disease. These somewhat unexpected results are coupled with SGLT-2 inhibitors’ known acute effect of improvement in glycemia, reduction in blood pressure, and weight loss. In this review, we summarize the mechanism of action of SGLT-2 inhibitors, the metabolic effects of this class of medication, and the remarkable results of cardiovascular safety trials. In addition, we discuss adverse effects associated with these medications and the current recommendations for the use of these agents in the management of diabetes.

scholarly journals Serum urate and cardiovascular events in the DCCT/EDIC study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alicia J. Jenkins ◽  
Barbara H. Braffett ◽  
Arpita Basu ◽  
Ionut Bebu ◽  
Samuel Dagogo-Jack ◽  
...  
Keyword(s):  
Cardiovascular Events ◽  
Serum Urate ◽  
Continuous Variable ◽  
Major Adverse Cardiovascular Events ◽  
Normal Range ◽  
The Metabolic Syndrome ◽  
Routine Measurement

AbstractIn type 2 diabetes, hyperuricemia is associated with cardiovascular disease (CVD) and the metabolic syndrome (MetS), but associations in type 1 diabetes (T1D) have not been well-defined. This study examined the relationships between serum urate (SU) concentrations, clinical and biochemical factors, and subsequent cardiovascular events in a well-characterized cohort of adults with T1D. In 973 participants with T1D in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study (DCCT/EDIC), associations were defined between SU, measured once in blood collected 1997–2000, and (a) concurrent MetS and (b) incident ‘any CVD’ and major adverse cardiovascular events (MACE) through 2013. SU was higher in men than women [mean (SD): 4.47 (0.99) vs. 3.39 (0.97) mg/dl, respectively, p < 0.0001], and was associated with MetS features in both (men: p = 0.0016; women: p < 0.0001). During follow-up, 110 participants (11%) experienced “any CVD”, and 53 (5%) a MACE. Analyzed by quartiles, SU was not associated with subsequent CVD or MACE. In women, SU as a continuous variable was associated with MACE (unadjusted HR: 1.52; 95% CI 1.07–2.16; p = 0.0211) even after adjustment for age and HbA1c (HR: 1.47; 95% CI 1.01–2.14; p = 0.0467). Predominantly normal range serum urate concentrations in T1D were higher in men than women and were associated with features of the MetS. In some analyses of women only, SU was associated with subsequent MACE. Routine measurement of SU to assess cardiovascular risk in T1D is not merited.Trial registration clinicaltrials.gov NCT00360815 and NCT00360893.

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