Mixed-effects modelling to quantify the effect of empagliflozin on renal glucose reabsorption in patients with type 2 diabetes

2016 ◽  
Vol 18 (3) ◽  
pp. 241-248 ◽  
Author(s):  
J. Mondick ◽  
M. Riggs ◽  
T. Sasaki ◽  
A. Sarashina ◽  
U. C. Broedl ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Mixed Effects ◽  
Glucose Reabsorption ◽  
Renal Glucose Reabsorption

Mechanisms of Protective Effects of SGLT2 Inhibitors in Cardiovascular Disease and Renal Dysfunction

2019 ◽  
Vol 19 (20) ◽  
pp. 1818-1849 ◽  
Author(s):  
Ban Liu ◽  
Yuliang Wang ◽  
Yangyang Zhang ◽  
Biao Yan
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Renal Dysfunction ◽  
Sglt2 Inhibitors ◽  
Sodium Glucose Cotransporter ◽  
Glucose Reabsorption ◽  
Renal Glucose Reabsorption

: Type 2 diabetes mellitus is one of the most common forms of the disease worldwide. Hyperglycemia and insulin resistance play key roles in type 2 diabetes mellitus. Renal glucose reabsorption is an essential feature in glycaemic control. Kidneys filter 160 g of glucose daily in healthy subjects under euglycaemic conditions. The expanding epidemic of diabetes leads to a prevalence of diabetes-related cardiovascular disorders, in particular, heart failure and renal dysfunction. Cellular glucose uptake is a fundamental process for homeostasis, growth, and metabolism. In humans, three families of glucose transporters have been identified, including the glucose facilitators GLUTs, the sodium-glucose cotransporter SGLTs, and the recently identified SWEETs. Structures of the major isoforms of all three families were studied. Sodium-glucose cotransporter (SGLT2) provides most of the capacity for renal glucose reabsorption in the early proximal tubule. A number of cardiovascular outcome trials in patients with type 2 diabetes have been studied with SGLT2 inhibitors reducing cardiovascular morbidity and mortality. : The current review article summarises these aspects and discusses possible mechanisms with SGLT2 inhibitors in protecting heart failure and renal dysfunction in diabetic patients. Through glucosuria, SGLT2 inhibitors reduce body weight and body fat, and shift substrate utilisation from carbohydrates to lipids and, possibly, ketone bodies. These pleiotropic effects of SGLT2 inhibitors are likely to have contributed to the results of the EMPA-REG OUTCOME trial in which the SGLT2 inhibitor, empagliflozin, slowed down the progression of chronic kidney disease and reduced major adverse cardiovascular events in high-risk individuals with type 2 diabetes. This review discusses the role of SGLT2 in the physiology and pathophysiology of renal glucose reabsorption and outlines the unexpected logic of inhibiting SGLT2 in the diabetic kidney.

Targeting Renal Glucose Reabsorption for the Treatment of Type 2 Diabetes Mellitus Using the SGLT2 Inhibitor Dapagliflozin

2012 ◽  
Vol 124 (4) ◽  
pp. 62-73 ◽  
Author(s):  
Serge A. Jabbour ◽  
Jean M. Whaley ◽  
Mark Tirmenstein ◽  
Simon M. Poucher ◽  
Timothy P. Reilly ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Sglt2 Inhibitor ◽  
Glucose Reabsorption ◽  
Renal Glucose Reabsorption

scholarly journals New Insights into the Efficacy of Aspalathin and Other Related Phytochemicals in Type 2 Diabetes—A Review

2021 ◽  
Vol 23 (1) ◽  
pp. 356
Author(s):  
Christo J. F. Muller ◽  
Elizabeth Joubert ◽  
Nireshni Chellan ◽  
Yutaka Miura ◽  
Kazumi Yagasaki
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Receptor ◽  
Tyrosine Phosphatase ◽  
Dietary Exposure ◽  
Therapeutic Effects ◽  
Glucose Reabsorption ◽  
Flavone Derivatives ◽  
Renal Glucose Reabsorption

In the pursuit of bioactive phytochemicals as a therapeutic strategy to manage metabolic risk factors for type 2 diabetes (T2D), aspalathin, C-glucosyl dihydrochalcone from rooibos (Aspalathus linearis), has received much attention, along with its C-glucosyl flavone derivatives and phlorizin, the apple O-glucosyl dihydrochalcone well-known for its antidiabetic properties. We provided context for dietary exposure by highlighting dietary sources, compound stability during processing, bioavailability and microbial biotransformation. The review covered the role of these compounds in attenuating insulin resistance and enhancing glucose metabolism, alleviating gut dysbiosis and associated oxidative stress and inflammation, and hyperuricemia associated with T2D, focusing largely on the literature of the past 5 years. A key focus of this review was on emerging targets in the management of T2D, as highlighted in the recent literature, including enhancing of the insulin receptor and insulin receptor substrate 1 signaling via protein tyrosine phosphatase inhibition, increasing glycolysis with suppression of gluconeogenesis by sirtuin modulation, and reducing renal glucose reabsorption via sodium-glucose co-transporter 2. We conclude that biotransformation in the gut is most likely responsible for enhancing therapeutic effects observed for the C-glycosyl parent compounds, including aspalathin, and that these compounds and their derivatives have the potential to regulate multiple factors associated with the development and progression of T2D.

scholarly journals Characterization of Renal Glucose Reabsorption in Response to Dapagliflozin in Healthy Subjects and Subjects With Type 2 Diabetes

Diabetes Care ◽  
2013 ◽  
Vol 36 (10) ◽  
pp. 3169-3176 ◽  
Author(s):  
R. A. DeFronzo ◽  
M. Hompesch ◽  
S. Kasichayanula ◽  
X. Liu ◽  
Y. Hong ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Healthy Subjects ◽  
Glucose Reabsorption ◽  
Renal Glucose Reabsorption

scholarly journals Effect of tofogliflozin on arterial stiffness in patients with type 2 diabetes: prespecified sub-analysis of the prospective, randomized, open-label, parallel-group comparative UTOPIA trial

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Naoto Katakami ◽  
◽  
Tomoya Mita ◽  
Hidenori Yoshii ◽  
Toshihiko Shiraiwa ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Conventional Treatment ◽  
Mixed Effects ◽  
Mixed Effects Models ◽  
Open Label ◽  
Parallel Group ◽  
History Of

Abstract Background Tofogliflozin, an SGLT2 inhibitor, is associated with favorable metabolic effects, including improved glycemic control and serum lipid profile and decreased body weight, visceral adipose tissue, and blood pressure (BP). This study evaluated the effects of tofogliflozin on the brachial-ankle pulse wave velocity (baPWV) in patients with type 2 diabetes (T2DM) without a history of apparent cardiovascular disease. Methods The using tofogliflozin for possible better intervention against atherosclerosis for type 2 diabetes patients (UTOPIA) trial is a prospective, randomized, open-label, multicenter, parallel-group, comparative study. As one of the prespecified secondary outcomes, changes in baPWV over 104 weeks were evaluated in 154 individuals (80 in the tofogliflozin group and 74 in the conventional treatment group) who completed baPWV measurement at baseline. Results In a mixed-effects model, the progression in the right, left, and mean baPWV over 104 weeks was significantly attenuated with tofogliflozin compared to that with conventional treatment (– 109.3 [– 184.3, – 34.3] (mean change [95% CI] cm/s, p = 0.005; – 98.3 [– 172.6, – 24.1] cm/s, p = 0.010; – 104.7 [– 177.0, – 32.4] cm/s, p = 0.005, respectively). Similar findings were obtained even after adjusting the mixed-effects models for traditional cardiovascular risk factors, including body mass index (BMI), glycated hemoglobin (HbA1c), total cholesterol, high-density lipoprotein (HDL)-cholesterol, triglyceride, systolic blood pressure (SBP), hypertension, smoking, and/or administration of drugs, including hypoglycemic agents, antihypertensive agents, statins, and anti-platelets, at baseline. The findings of the analysis of covariance (ANCOVA) models, which included the treatment group, baseline baPWV, and traditional cardiovascular risk factors, resembled those generated by the mixed-effects models. Conclusions Tofogliflozin significantly inhibited the increased baPWV in patients with T2DM without a history of apparent cardiovascular disease, suggesting that tofogliflozin suppressed the progression of arterial stiffness. Trial Registration UMIN000017607. Registered 18 May 2015. (https://www.umin.ac.jp/icdr/index.html)

scholarly journals SODIUM-GLUCOSE LINKED COTRANSPORTER 2 INHIBITOR: A NEW HORIZON IN THE TREATMENT OF TYPE-2 DIABETES

2021 ◽  
pp. 45-48
Author(s):  
REKHA BISHT
Keyword(s):  
Type 2 Diabetes ◽  
Adverse Effects ◽  
Antidiabetic Drugs ◽  
Diabetic Patients ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Sodium Glucose Cotransporter ◽  
Glucose Reabsorption ◽  
Glycemic Targets

Hyperglycemia is a key therapeutic focus in the management of patients with type 2 diabetes (T2D) mellitus. The various therapeutic classes of antidiabetic drugs presently existing in the market are not sufficiently effective in maintaining long-term glycemic control in most of the diabetic patients, even when used in combination. The undesirable adverse effects of these drugs, such as hypoglycemia, weight gain, and hepatic and renal toxicity, have escalated the demand for the discovery of new and safer antidiabetic drugs. The progressive nature of T2D requires practitioners to periodically evaluate patients and intensify glucose-lowering treatment once glycemic targets are not attained. Sodium-glucose cotransporter 2 inhibitors (SGLT2-is) are the new class of antidiabetic medications that are approved (2013) by the Food and Drug Administration recently for treating diabetes. These inhibitors block the SGLT2 protein involved in glucose reabsorption from the proximal renal tubule resulting in escalated glucose excretion and lower blood glucose levels. These inhibitors exhibit favorable effects beyond glucose control, such as consistent body weight, blood pressure, and serum uric acid reductions. This review highlighted the brief updates of SGLT2-i, their benefits, and adverse effects.

P1050THE EFFICACY AND RENAL SAFETY OF SWITCHING FROM DAPAGLIFLOZIN TO EMPAGLIFLOZIN IN PATIENTS WITH TYPE 2 DIABETES

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
AI-YU YANG ◽  
Hung-Chun Chen
Keyword(s):  
Type 2 Diabetes ◽  
Hba1c Level ◽  
Adverse Reactions ◽  
Primary Outcome Measure ◽  
Glucose Reabsorption ◽  
Before And After ◽  
The Difference ◽  
Effective Group ◽  
Renal Safety

Abstract Background and Aims Both dapagliflozin (DPG) and empagliflozin (EPG) are highly selective sodium-glucose cotransporter-2 (SGLT-2) inhibitors that inhibit glucose reabsorption and increase its excretion in urine. Previously, DPG was limited to patients with an estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2, while EPG can be used for those with an eGFR ≥ 45 mL/min/1.73 m2. Therefore DPG was switched to EPG in many patients when eGFR decreased. However, the clinical efficacy and safety of these switches are not clear. In this study, we compared the efficacy and renal safety between patients switching from DPG to EPG and those continuing DPG in patients with type 2 diabetes mellitus (T2DM). Method This retrospective observational study included patients with T2DM who were treated with DPG for more than 6 months. This study included patients who switched to EPG and those who continued using DPG. All other hypoglycemic drugs were maintained at the same dosage before and after the study period. The primary outcome measure was the change in hemoglobin A1c (HbA1c) level after 6 months. The EPG group was evaluated for whether the hypoglycemic effect remain effective after drug switching. Patients with HbA1c levels at or lower than the baseline value after 6 months were defined as effective and patients with levels higher than the baseline were defined as invalid. Safety was evaluated by comparing the difference of eGFR between the baseline value and six months after treatment. Results This study included 169 patients. Among them, 72 patients continued DPG and 97 patients switched to EPG. HbA1c level decreased significantly only in EPG group. In EPG group, 59 patients belong to the effective group (60.8%) and 38 patients were invalid (39.2%). There was no significant change in eGFR after treatment in both groups. Ten patients in DPG group develop adverse reactions (three patients felt uncomfortable and seven patients had urinary tract symptoms), but all continued treatment. In EPG group, five patients lacked follow-up records during the study period and it was difficult to determine whether the patient’s willingness to continue treatment was affected by adverse reactions. Conclusion Our study showed that switching from DPG to EPG in patients with T2DM was effective for blood glucose maintenance and caused no significant changes in renal function. In addition, no severe drug-related adverse reactions were found.

scholarly journals Diabetes Research Open Access: Sodium Glucose Cotransporter2 (SGLT2) Inhibitors

2020 ◽  
Vol 2 (S1) ◽  
pp. 14
Author(s):  
Kuşkonmaz SM
Keyword(s):  
Sglt2 Inhibitors ◽  
Diabetes Research ◽  
Oral Antidiabetics ◽  
First Line ◽  
Glucose Lowering ◽  
Sodium Glucose Cotransporter ◽  
Glucose Reabsorption ◽  
New Guidelines ◽  
Renal Glucose Reabsorption

Sodium glucose cotransporter 2 (SGLT2) inhibitors (SGLT2i) are a group of glycosuric drugs approved in the management of type 2 diabetes mellitus. They act on the sodium glucose cotransporter and inhibit renal glucose reabsorption. Canagliflozin dapagliflozin and empagliflozin are members of the SGLT2i group. SGLT2 is supposed to be unique to the kidney. Recent studies showed the benefits of these agents beyond and independent from glucose lowering. New guidelines emphasize these pleiotropic effects such as cardioprotective and renoprotective effects of SGLT2i and suggest them as first line oral antidiabetics in patients with coronary heart disease.

Sign in / Sign up

Export Citation Format

Share Document