Influence of Renal Function on the 52-Week Efficacy and Safety of the Sodium Glucose Cotransporter 2 Inhibitor Luseogliflozin in Japanese Patients with Type 2 Diabetes Mellitus

Haneda, Masakazu; Seino, Yutaka; Inagaki, Nobuya; Kaku, Kohei; Sasaki, Takashi; Fukatsu, Atsushi; Kakiuchi, Haruka; Sato, Yuri; Sakai, Soichi; Samukawa, Yoshishige

doi:10.1016/j.clinthera.2015.10.025

Cited by 61 publications

(70 citation statements)

References 33 publications

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“…Furthermore, consistently, both bodyweight and blood pressure also decreased with canagliflozin treatment. A similar renal function‐dependent reduction in HbA1c in patients with type 2 diabetes was also reported using luseogliflozin 2.5 mg daily.…”

Section: Effects Of Glomerular Function On Glycemic Controlsupporting

confidence: 63%

Metabolic and hemodynamic effects of sodium‐dependent glucose cotransporter 2 inhibitors on cardio‐renal protection in the treatment of patients with type 2 diabetes mellitus

Kashiwagi¹,

Maegawa

2017

J of Diabetes Invest

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The specific sodium–glucose cotransporter 2 inhibitors (SGLT2 inhibitors) inhibit glucose reabsorption in proximal renal tubular cells, and both fasting and postprandial glucose significantly decrease because of urinary glucose loss. As a result, pancreatic β‐cell function and peripheral insulin action significantly improve with relief from glucose toxicity. Furthermore, whole‐body energy metabolism changes to relative glucose deficiency and triggers increased lipolysis in fat cells, and fatty acid oxidation and then ketone body production in the liver during treatment with SGLT2 inhibitors. In addition, SGLT2 inhibitors have profound hemodynamic effects including diuresis, dehydration, weight loss and lowering blood pressure. The most recent findings on SGLT2 inhibitors come from results of the Empagliflozin, Cardiovascular Outcomes and Mortality in Type 2 Diabetes trial. SGLT2 inhibitors exert extremely unique and cardio‐renal protection through metabolic and hemodynamic effects, with long‐term durability on the reduction of blood glucose, bodyweight and blood pressure. Although a site of action of SGLT2 inhibitors is highly specific to inhibit renal glucose reabsorption, whole‐body energy metabolism, and hemodynamic and renal functions are profoundly modulated during the treatment of SGLT2 inhibitors. Previous studies suggest multifactorial clinical benefits and safety concerns of SGLT2 inhibitors. Although ambivalent clinical results of this drug are still under active discussion, the present review summarizes promising recent evidence on the cardio‐renal and metabolic benefits of SGLT2 inhibitors in the treatment of type 2 diabetes.

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Section: Effects Of Glomerular Function On Glycemic Controlsupporting

confidence: 63%

Metabolic and hemodynamic effects of sodium‐dependent glucose cotransporter 2 inhibitors on cardio‐renal protection in the treatment of patients with type 2 diabetes mellitus

Kashiwagi¹,

Maegawa

2017

J of Diabetes Invest

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“…It is of significance that, in Japanese type 2 diabetes patients with a moderate BMI, we observed a significant increase in the adiponectin level through SGLT2‐i treatment, along with the observation of the time‐course profile of the body composition. A significant decrease in urine albumin excretion was also observed, supporting a favorable effect on the kidney …”

Section: Discussionmentioning

confidence: 62%

Sodium–glucose cotransporter 2 inhibitor‐induced changes in body composition and simultaneous changes in metabolic profile: 52‐week prospective LIGHT (Luseogliflozin: the Components of Weight Loss in Japanese Patients with Type 2 Diabetes Mellitus) Study

Sasaki

Sato

Fukuda

2018

J of Diabetes Invest

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“…In total, 27 studies yeilded data on biomarkers or on cardiovascular, renal or safety outcomes, with substantial contributions from three large cardiovascular outcome trials of empagliflozin, canagliflozin and dapagliflozin . Of the 27 studies, 18 were individual trials, eight were pooled analyses and one was a regulatory report for ertugliflozin (Figure and Supporting Information Table S2). The eight pooled analyses and one regulatory report combined data from 41 individual trials from which results were not individually available for the CKD population.…”

Section: Resultsmentioning

confidence: 99%

Effect of SGLT2 inhibitors on cardiovascular, renal and safety outcomes in patients with type 2 diabetes mellitus and chronic kidney disease: A systematic review and meta‐analysis

Toyama

Neuen

Jun

et al. 2019

Diabetes Obesity Metabolism

235

159

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Aim The use of sodium glucose co‐transporter 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) has been limited, primarily because glycaemic efficacy is dependent on kidney function. We performed a systematic review and meta‐analysis to assess the efficacy and safety of SGLT2 inhibitors in patients with T2DM and CKD, defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Materials and methods We searched MEDLINE, EMBASE and the Cochrane Library until 7 August 2018 and websites of the US, European and Japanese regulatory authorities until 27 July 2018 for data from randomized controlled trials of SGLT2 inhibitors that included reporting of effects on biomarkers, cardiovascular, renal or safety outcomes in individuals with T2DM and CKD. Random effects models and inverse variance weighting were used to calculate relative risks with 95% confidence intervals. Results Data were obtained from 27 studies with up to 7363 participants involved. In patients with T2DM and CKD, SGLT2 inhibitors lowered glycated haemoglobin (−0.29%; 95% CI, −0.39 to −0.19) as well as blood pressure, body weight and albuminuria. SGLT2 inhibition reduced the risk of cardiovascular death, nonfatal myocardial infarction or nonfatal stroke (RR, 0.81; 95% CI, 0.70‐0.94) and heart failure (RR, 0.61; 95% CI, 0.48‐0.78), without a clear effect on all‐cause mortality (HR, 0.86; 95% CI, 0.73‐1.01). These agents also attenuated the annual decline in eGFR slope (placebo‐subtracted difference of 1.35 mL/1.73 m2/y; 95% CI, 0.78‐1.93) and reduced the risk of the composite renal outcome (HR, 0.71; 95% CI, 0.53‐0.95). There was no evidence of additional risks with SGLT2 inhibition in CKD beyond those already known for the class, although heterogeneity was observed across individual agents for some safety outcomes. Conclusion Currently available data suggest that, despite only modest reductions in glycated haemoglobin, SGLT2 inhibitors reduce the risk of cardiovascular and renal outcomes in patients with T2DM and CKD, without clear evidence of additional safety concerns.

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Influence of Renal Function on the 52-Week Efficacy and Safety of the Sodium Glucose Cotransporter 2 Inhibitor Luseogliflozin in Japanese Patients with Type 2 Diabetes Mellitus

Cited by 61 publications

References 33 publications

Metabolic and hemodynamic effects of sodium‐dependent glucose cotransporter 2 inhibitors on cardio‐renal protection in the treatment of patients with type 2 diabetes mellitus

Metabolic and hemodynamic effects of sodium‐dependent glucose cotransporter 2 inhibitors on cardio‐renal protection in the treatment of patients with type 2 diabetes mellitus

Sodium–glucose cotransporter 2 inhibitor‐induced changes in body composition and simultaneous changes in metabolic profile: 52‐week prospective LIGHT (Luseogliflozin: the Components of Weight Loss in Japanese Patients with Type 2 Diabetes Mellitus) Study

Effect of SGLT2 inhibitors on cardiovascular, renal and safety outcomes in patients with type 2 diabetes mellitus and chronic kidney disease: A systematic review and meta‐analysis

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