Faculty Opinions recommendation of Dulaglutide versus insulin glargine in patients with type 2 diabetes and moderate-to-severe chronic kidney disease (AWARD-7): a multicentre, open-label, randomised trial.

Background: Treatment with bardoxolone methyl (Bard) in a multinational phase 3 trial, Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes (BEACON), resulted in increases in estimated glomerular filtration rate with concurrent reductions in serum magnesium. We analyzed data from several trials to characterize reductions in magnesium with Bard. Methods: BEACON randomized patients (n = 2,185) with type 2 diabetes (T2DM) and stage 4 chronic kidney disease (CKD) 1:1 to receive Bard (20 mg) or placebo once daily. In a separate open-label study, magnesium levels from 24-hour urine and sublingual epithelial cell samples were analyzed in patients with stage 3b-4 CKD and T2DM administered 20 mg Bard for 56 consecutive days. Results: BEACON patients randomized to Bard experienced significant reductions in serum magnesium from baseline relative to patients randomized to placebo (–0.17 mEq/L, 95% CI –0.18 to –0.60 mEq/L; p < 0.001). A separate study showed intracellular and urinary magnesium levels were unchanged with Bard treatment. Conclusions: Bard treatment results in significant decreases in serum magnesium that are not associated with changes in intracellular and urinary magnesium levels, indicating that magnesium decreases are not due to renal magnesium wasting or total body magnesium depletion. Importantly, the decreases in serum magnesium with Bard are not associated with adverse effects on QT interval.

Download Full-text

Exenatide once weekly versus insulin glargine for type 2 diabetes (DURATION-3): 3-year results of an open-label randomised trial

The Lancet Diabetes & Endocrinology ◽

10.1016/s2213-8587(14)70029-4 ◽

2014 ◽

Vol 2 (6) ◽

pp. 464-473 ◽

Cited By ~ 104

Author(s):

Michaela Diamant ◽

Luc Van Gaal ◽

Bruno Guerci ◽

Stephen Stranks ◽

Jenny Han ◽

...

Keyword(s):

Type 2 Diabetes ◽

Insulin Glargine ◽

Randomised Trial ◽

Diabetes Duration ◽

Open Label

Download Full-text

The Comparison of 24-Hour Urinary Sodium, Albumin, and Protein Excretion in Chronic Kidney Disease Patients with Type 2 Diabetes Mellitus Using Insulin Detemir or Insulin Glargine

Clinical Drug Investigation ◽

10.1007/s40261-013-0118-5 ◽

2013 ◽

Vol 33 (10) ◽

pp. 773-778

Author(s):

Baris Afsar

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Chronic Kidney Disease ◽

Type 2 Diabetes Mellitus ◽

Kidney Disease ◽

Insulin Glargine ◽

Insulin Detemir ◽

Urinary Sodium ◽

Protein Excretion

Download Full-text

Renoprotective effects of canagliflozin, a sodium glucose cotransporter 2 inhibitor, in type 2 diabetes patients with chronic kidney disease: A randomized open-label prospective trial

Diabetes and Vascular Disease Research ◽

10.1177/1479164118782872 ◽

2018 ◽

Vol 15 (5) ◽

pp. 469-472 ◽

Cited By ~ 10

Author(s):

Hiroyuki Takashima ◽

Yoshinori Yoshida ◽

Chinami Nagura ◽

Tetsuya Furukawa ◽

Ritsukou Tei ◽

...

Keyword(s):

Type 2 Diabetes ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Adverse Events ◽

Prospective Trial ◽

Control Group ◽

Open Label ◽

And Control ◽

Diabetes Patients

Background: To evaluate the renoprotective effects of canagliflozin, we assessed the albuminuria-lowering effect in Japanese type 2 diabetes patients with chronic kidney disease (CKD). Methods: In this prospective, open-label, parallel-group study, type 2 diabetes patients with CKD were randomized to receive either oral canagliflozin (100 mg/day) or usual care (control group) for 52 weeks. Endpoints included changes in urinary albumin-to-creatinine ratio (UACR), other urinary biomarkers, laboratory parameters, and adverse events. Results: Both groups included 20 patients in the analysis. Mean changes in UACR was −83 (−266 to −31) mg/gCr and 27 (−11 to 131) mg/gCr, in the canagliflozin and control groups, respectively ( p = 0.004). Urinary liver-type free acid binding protein, N-acetyl-β-d-glucosaminidase, and β2-microglobulin levels were also significantly decreased in the canagliflozin group, but not in the control group. Mean change in estimated glomerular filtration rate at the end of the study was 0.7 and −3.4 mL/min/1.73 m2 in the canagliflozin and control group, respectively ( p = 0.024). Canagliflozin treatment led to improvement of glycaemic control and reduction in body weight, blood pressure, and liver transaminase. There were no adverse events associated with canagliflozin. Conclusion: Canagliflozin was associated with slower progression of kidney disease and reduction in albuminuria and tubulointerstitial markers in diabetes patients with CKD.

Download Full-text

Rationale and design of an investigator-initiated, multicenter, prospective open-label, randomized trial to evaluate the effect of ipragliflozin on endothelial dysfunction in type 2 diabetes and chronic kidney disease: the PROCEED trial

Cardiovascular Diabetology ◽

10.1186/s12933-020-01065-w ◽

2020 ◽

Vol 19 (1) ◽

Author(s):

Atsushi Tanaka ◽

◽

Michio Shimabukuro ◽

Yosuke Okada ◽

Kazuhiro Sugimoto ◽

...

Keyword(s):

Type 2 Diabetes ◽

Chronic Kidney Disease ◽

Endothelial Dysfunction ◽

Kidney Disease ◽

Therapeutic Target ◽

Analysis Of Covariance ◽

Renal Outcome ◽

Open Label ◽

Therapeutic Benefits

Abstract Background Type 2 diabetes (T2D) is associated with renal impairment and vascular endothelial dysfunction. Therefore, this pathological connection is an important therapeutic target. Recent cardiovascular and renal outcome trials demonstrated that sodium glucose cotransporter 2 inhibitors (SGLT2is) consistently reduced the risks of cardiovascular and renal events and mortality in patients with T2D and various other background risks including chronic kidney disease (CKD). However, the precise mechanisms by which SGLT2is accords these therapeutic benefits remain uncertain. It is also unknown whether these SGLT2is-associated benefits are associated with the amelioration of endothelial dysfunction in patients with T2D and CKD. Methods The PROCEED trial is an investigator-initiated, prospective, multicenter, open-label, randomized-controlled trial. The target sample size is 110 subjects. After they furnish informed consent and their endothelial dysfunction is confirmed from their decreased reactive hyperemia indices (RHI), eligible participants with T2D (HbA1c, 6.0–9.0%) and established CKD (30 mL/min/1.73 m2 ≤ estimated glomerular filtration ratio [eGFR] < 60 and/or ≥ urine albumin-to-creatinine ratio 30 mg/g Cr) will be randomized (1:1) to receive either 50 mg ipragliflozin daily or continuation of background treatment (non-SGLT2i). The primary endpoint is the change in RHI from baseline after 24 weeks. To compare the treatment effects between groups, the baseline-adjusted means and their 95% confidence intervals will be estimated by analysis of covariance adjusted for HbA1c (< 7.0% or ≥ 7.0%), age (< 70 y or ≥ 70 y), RHI (< 1.67 or ≥ 1.67), eGFR (< 45 mL/min/1.73 m2 or ≥ 45 mL/min/1.73 m2), and smoking status. Prespecified responder analyses will be also conducted to determine the proportions of patients with clinically meaningful changes in RHI at 24 weeks. Discussion PROCEED is the first trial to examine the effects of ipragliflozin on endothelial dysfunction in patients with T2D and CKD. This ongoing trial will establish whether endothelial dysfunction is a therapeutic target of SGLT2is in this population. It will also provide deep insights into the potential mechanisms by which SGLT2is reduced the risks of cardiovascular and renal events in recent outcome trials. Trial registration Unique Trial Number, jRCTs071190054 (https://jrct.niph.go.jp/en-latest-detail/jRCTs071190054).

Download Full-text