LX4211 Therapy Reduces Postprandial Glucose Levels in Patients With Type 2 Diabetes Mellitus and Renal Impairment Despite Low Urinary Glucose Excretion

2015 ◽  
Vol 37 (1) ◽  
pp. 71-82.e12 ◽  
Author(s):  
Brian Zambrowicz ◽  
Pablo Lapuerta ◽  
Paul Strumph ◽  
Phillip Banks ◽  
Alan Wilson ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Renal Impairment ◽  
Postprandial Glucose ◽  
Urinary Glucose Excretion ◽  
Glucose Levels ◽  
Urinary Glucose ◽  
Glucose Excretion

Abstract 11267: LX4211, a Dual Inhibitor of Sodium-Glucose Cotransporters 1 and 2, Reduces Systolic Blood Pressure in Patients With Type 2 Diabetes Mellitus and Moderate to Severe Renal Impairment

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Pablo Lapuerta ◽  
Paul Strumph ◽  
Philip Banks ◽  
Ikenna Ogbaa ◽  
Brian Zambrowicz ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Renal Impairment ◽  
Systolic Blood Pressure ◽  
Severe Renal Impairment ◽  
Postprandial Glucose ◽  
Dual Inhibitor

Introduction: Selective sodium-glucose cotransporter 2 (SGLT2) inhibitors target only the kidney, and they have reduced efficacy when patients with type 2 diabetes mellitus (T2DM) have renal impairment (RI). LX4211 blocks sodium and glucose absorption in the gastrointestinal tract by inhibition of SGLT1, and it enhances urinary sodium and glucose excretion in the urine through inhibition of SGLT2. The dual SGLT1/2 action of LX4211 was anticipated to reduce systolic blood pressure (SBP) in addition to improving glucose control in the setting of RI. Methods: This analysis explored the effect of LX4211 on SBP in a clinical trial of patients with T2DM and moderate to severe RI. Patients (N=31) were randomly assigned to be treated with LX4211 (400 mg, N=16) or placebo (N=15) qd for 7 consecutive days. Postprandial glucose levels after a standard high glucose meal served as the primary measure of pharmacodynamic activity. Baseline and Day 8 trough SBP measures were each an average of 3 seated assessments. Results: Mean baseline characteristics included age 66.4 years, estimated glomerular filtration rate (eGFR) 43.4 mL/min/1.73 m 2 , and SBP 130.9 mmHg. Postprandial glucose area under the curve (sampled from pre-dose to 4 hours post meal) was reduced from Baseline to Day 7 by 169.3 mg*hr/dL on LX4211 compared to placebo (p=0.003). Day 8 SBP reductions were 11.4 mmHg on LX4211 and 0.0 mmHg on placebo (p=0.045 for difference between groups). Patients with greater RI (eGFR <45 mL/min/1.73 m2) treated with LX4211 (N=6) had a 10.5 mmHg SBP reduction compared to 0.3 mmHg on placebo (N=9). The difference between seated and standing SBP did not change with LX4211 (0.0 mmHg change, Day 8 vs. Baseline). There were no reports of hypotension, hypovolemia, no serious adverse events, and no patient discontinued due to an adverse event. Mild hypoglycemia was reported in 1 LX4211 patient compared to 2 placebo patients. Conclusions: LX4211 may reduce SBP and enhance glycemic control in T2DM patients with moderate to severe RI.

Influence of Diabetogenic Factors on Fasting and Postprandial Glucose Levels in Patients with Type 2 Diabetes Mellitus

2019 ◽  
Vol 17 (9) ◽  
pp. 465-471
Author(s):  
Yuan-Tung Chang ◽  
Chung-Ze Wu ◽  
Chang-Hsun Hsieh ◽  
Jin-Biou Chang ◽  
Yao-Jen Liang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Postprandial Glucose ◽  
Glucose Levels

scholarly journals Effects of Acute Resistance Exercise with and without Whole-Body Electromyostimulation and Endurance Exercise on the Postprandial Glucose Regulation in Patients with Type 2 Diabetes Mellitus: A Randomized Crossover Study

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4322
Author(s):  
Roman Holzer ◽  
Benedikt Schulte-Körne ◽  
Jan Seidler ◽  
Hans-Georg Predel ◽  
Christian Brinkmann
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Resistance Exercise ◽  
Endurance Exercise ◽  
Postprandial Glucose ◽  
Whole Body ◽  
Moderate Intensity ◽  
Glucose Levels

Background: Long hyperglycemic episodes trigger complications in type 2 diabetes mellitus (T2DM) patients. Postprandial glucose excursions can be reduced by acute physical activity. However, it is not yet clear which type of exercise has the best effect on postprandial glucose levels. Methods: Six T2DM patients participated in three 20-min moderate-intensity exercise sessions after breakfast in a randomized order: resistance exercise with whole-body electromyostimulation (WB-EMS), resistance exercise without electromyostimulation (RES) and cycling endurance exercise (END). A continuous glucose monitoring system recorded glucose dynamics. Results: Postprandially-increased glucose levels decreased in all cases. Time to baseline (initial value prior to meal intake) was quite similar for WB-EMS, RES and END. Neither glucose area under the curve (AUC), nor time in range from the start of the experiment to its end (8 h later) differed significantly. A Friedman analysis of variance, however, revealed an overall significant difference for AUC in the post-exercise recovery phase (END seems to have superior effects, but post-hoc tests failed statistical significance). Conclusions: There are no notable differences between the effects of the different types of exercise on glucose levels, especially when comparing values over a longer period of time.

scholarly journals Effect of Renal Impairment on the Pharmacokinetics and Pharmacodynamics of Tofogliflozin (A SELECTIVE SGLT2 Inhibitor) in Patients with Type 2 Diabetes Mellitus

Drug Research ◽  
2018 ◽  
Vol 69 (06) ◽  
pp. 314-322 ◽  
Author(s):  
Sachiya Ikeda ◽  
Yasuki Takano ◽  
Dietmar Schwab ◽  
Agnes Portron ◽  
Nahoko Kasahara-Ito ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Renal Function ◽  
Renal Impairment ◽  
Normal Renal Function ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Urinary Glucose ◽  
Dose Study

Abstract Purpose Tofogliflozin is an orally available selective inhibitor of sodium-glucose co-transporter 2 for treatment of type 2 diabetes mellitus (T2DM). Two studies were conducted to evaluate the effect of renal impairment on pharmacokinetics and pharmacodynamics of tofogliflozin. Methods The studies were: 1) single dose study in T2DM patients with normal renal function and mild, moderate and severe renal impairment, and 2) multiple dose study for 24 weeks in T2DM patients with normal renal function and moderate renal impairment. Results Renal function did not have a clinically relevant effect on the PK of tofogliflozin. Urinary glucose excretion up to 24 h after administration of tofogliflozin (UGE24h) decreased with decreasing glomerular filtration rate. Lowering UGE24h resulted in waning glycemic control but not body weight reduction. Conclusions Single and multiple administrations of tofogliflozin were generally well tolerated in T2DM patients with various renal functions. As far as investigated here, these studies indicate no dose adjustment is required for patients with renal impairment.

scholarly journals The frequency of Tim-3 on circulating Tfh cells was increased in type 2 diabetes mellitus patients

2020 ◽  
Vol 18 ◽  
pp. 205873922098280
Author(s):  
Shuai Guo ◽  
Xujie Yu ◽  
Limei Wang ◽  
Jing Jing ◽  
Yuanyuan Sun ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
High Glucose ◽  
C Peptide ◽  
Glucose Levels ◽  
Tfh Cells ◽  
Fasting Plasma ◽  
Healthy Donors

Type 2 diabetes mellitus (T2DM) is a chronic, low-grade inflammation disease. T follicular helper (Tfh) cells and T cell immunoglobulin and mucin domain 3 (Tim-3) are implicated in many immune diseases. This study aims to explore whether Tim-3 expression on Tfh cells is associated with T2DM progression. White blood cells (WBCs) were harvested from 30 patients with T2DM and 20 healthy donors. The abundance of circulating Tfh cells (cTfh) and the frequency of Tim-3 were analyzed by flow cytometry. Levels of fasting plasma glucose (FPG), insulin, hemoglobin A1C (HbA1C), and fasting plasma C-peptide were measured. Body mass index (BMI) and diabetes duration were also recorded. Patients with T2DM had higher numbers of cTfh cells. In addition, cTfh cells showed a negative correlation with HbA1C and diabetes duration, a positive correlation with fasting plasma C-peptide. The frequency of Tim-3 on cTfh cells was higher among T2DM patients compared with healthy donors. The in vitro experiment showed that high glucose levels increased the abundance cTfh cells but had no effect on Tim-3 expression. Our results suggest that cTfh cells and associated Tim-3 frequency may contribute to the progression of T2DM, and high glucose levels may influence cTfh cells directly.

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