Results of the glucose-lowering effect of WelChol study (GLOWS): A randomized, double-blind, placebo-controlled pilot study evaluating the effect of colesevelam hydrochloride on glycemic control in subjects with type 2 diabetes

Abstract Purpose Diabesity, the combination of obesity and type 2 diabetes, is an ever-growing global health burden. Diabesity-associated dysbiosis of the intestinal microbiome has gained attention as a potential driver of disease and, therefore, a possible therapeutic target by means of pro- or prebiotic supplementation. This study tested the effects of a multispecies synbiotic (i.e. a combination of probiotics and prebiotics) on glucose metabolism, gut microbiota, gut permeability, neutrophil function and quality of life in treatment-experienced diabesity patients. Methods A randomized, double-blind, placebo-controlled pilot study with 26 diabesity patients was conducted in which patients received a daily dose of a multispecies probiotic and a prebiotic (or a placebo) for 6 months. Results There were no changes in glucose metabolism or mixed meal tolerance test responses throughout the study. The analysis of secondary outcomes revealed beneficial effects on hip circumference [− 1 (95% CI − 4; 3) vs +3 (− 1; 8) cm, synbiotics vs. placebo, respectively, p = 0.04], serum zonulin [− 0.04 (− 0.2; 0.1) vs +0.3 (− 0.05; 0.6) ng/ml, p = 0.004)] and the physical role item of the SF36 quality of life assessment [+ 5.4 (− 1.7; 12.5) vs − 5.0 (− 10.1; 0.2) points, p = 0.02] after 3 months of intervention, and lipoprotein (a) [− 2.1 (− 5.7; 1.6) vs +3.4 (− 0.9; 7.9) mg/dl, p = 0.02] after 6 months. There were no significant differences in alpha or beta diversity of the microbiome between groups or time points. Conclusions Glucose metabolism as the primary outcome was unchanged during the intervention with a multispecies synbiotic in patients with diabesity. Nevertheless, synbiotics improved some symptoms and biomarkers of type 2 diabetes and aspects of quality of life suggesting a potential role as adjuvant tool in the management of diabesity. Graphic abstract

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Rapid and dramatic glucose‐lowering effect of bromocriptine in an inadequately controlled type 2 diabetes patient with prolactinoma

Journal of Diabetes Investigation ◽

10.1111/jdi.13369 ◽

2020 ◽

Author(s):

Motoyuki Igata ◽

Yoshitaka Yagi ◽

Satoko Hanatani ◽

Masaji Sakaguchi ◽

Norio Ishii ◽

...

Keyword(s):

Type 2 Diabetes ◽

Diabetes Patient ◽

Glucose Lowering ◽

Lowering Effect ◽

Glucose Lowering Effect

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SLC47A1 gene rs2289669 G>A variants enhance the glucose-lowering effect of metformin via delaying its excretion in Chinese type 2 diabetes patients

Diabetes Research and Clinical Practice ◽

10.1016/j.diabres.2015.05.003 ◽

2015 ◽

Vol 109 (1) ◽

pp. 57-63 ◽

Cited By ~ 24

Author(s):

Rui He ◽

Dandan Zhang ◽

Wei Lu ◽

Taishan Zheng ◽

Lili Wan ◽

...

Keyword(s):

Type 2 Diabetes ◽

Glucose Lowering ◽

Lowering Effect ◽

Glucose Lowering Effect ◽

Diabetes Patients

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What Characteristics at Baseline Are Associated with the Glucose-lowering Effect of Colestimide in Patients with Type 2 Diabetes and Hypercholesterolemia According to Response to Treatment?

Journal of Nippon Medical School ◽

10.1272/jnms.80.211 ◽

2013 ◽

Vol 80 (3) ◽

pp. 211-217 ◽

Cited By ~ 2

Author(s):

Tatsuya Suzuki ◽

Misako Tsunoda-Kubota ◽

Junya Aoyama ◽

Shoko Futami-Suda ◽

Masao Hashimoto ◽

...

Keyword(s):

Type 2 Diabetes ◽

Response To Treatment ◽

Glucose Lowering ◽

Lowering Effect ◽

Glucose Lowering Effect

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The DAWN study of dorzagliatin as add-on therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, phase 3 trial

10.21203/rs.3.rs-733332/v1 ◽

2021 ◽

Author(s):

Li Chen ◽

Wenying Yang ◽

Dalong Zhu ◽

Xiaoying Li ◽

Shenglian Gan ◽

...

Keyword(s):

Type 2 Diabetes ◽

Glycemic Control ◽

Plasma Glucose ◽

Tolerability Profile ◽

Model Assessment ◽

Homeostasis Model Assessment ◽

Phase 3 ◽

Double Blind ◽

Double Blind Placebo

Abstract Metformin is the first-line therapy for the treatment of type 2 diabetes (T2D) through mechanism of reduction in hepatic glucose production and fasting plasma glucose. Dorzagliatin is a novel glucokinase activator (GKA) that improves glucose and insulin sensitivity which significantly reduces post meal plasma glucose. Combination of dorzagliatin with metformin would offer benefits through the synergy of two mechanisms. In this randomized, double-blind, placebo-controlled phase 3 trial (NCT03141073), the efficacy and safety of dorzagliatin add-on to metformin in T2D patients were assessed. Eligible T2D patients (n=767) were randomly assigned in a 1:1 ratio to dorzagliatin group or placebo group add-on to metformin (1500 mg/day) for a 24-week double-blind treatment, then followed by a 28-week open-label treatment with dorzagliatin in all patients. The primary efficacy endpoint was the change from baseline in the glycated hemoglobin(HbA1c) level at week 24 and the safety was assessed throughout the trial. At week 24, the HbA1c was reduced from baseline in dorzagliatin group, superior to placebo (-1.02% vs. -0.36%; ETD, -0.66%; 95% CI, -0.79 to -0.53; P<0.0001), with the effects sustained through 52 weeks. The 2-hour postprandial glucose (2hPPG) was significantly decreased in dorzagliatin group over placebo (-98.10 mg/dl vs. -53.46 mg/dl, P<0.0001), and the homeostasis model assessment 2-β (HOMA2-β) and homeostasis model assessment 2-IR (HOMA 2-IR) were significantly improved at week 24 over placebo. The incidence of adverse events (AEs) was similar between the two groups during the 24 weeks. The hypoglycemia occurred in 4 (1.0%) out of 382 patients in dorzagliatin group during the 52 weeks. No severe hypoglycemia events were reported. In T2D patients with inadequate glycemic control by metformin alone, dorzagliatin demonstrated fast onset and sustained glycemic control with a good safety and tolerability profile for 52 weeks.

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