Comparison of Glycemic and Lipid Response to Pioglitazone Treatment in Mexican-Americans and Non-Hispanic Caucasians With Type 2 Diabetes

King, Allen B.; Armstrong, Dana; Chinnapongse, Sithiphol

doi:10.2337/diacare.26.1.245

Cited by 8 publications

(4 citation statements)

References 5 publications

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“…A number of studies examined racial or ethnic groups and all noted that results among these populations (Mexican-Americans and Hispanics [67], an Indian and Pakistani population in the United Kingdom [16,17,40], and a mixed Asian and Caucasian population [68]) were similar to those reported in largely Caucasian populations.…”

Section: Type 2 Diabetesmentioning

confidence: 54%

Comparative Effectiveness of Pioglitazone and Rosiglitazone in Type 2 Diabetes, Prediabetes,and the Metabolic Syndrome: A Meta-Analysis

Norris

Carson

Roberts

2007

CDR

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Objective -To assess the comparative efficacy and safety of pioglitazone and rosiglitazone.Research design and methods -Multiple electronic databases were searched for randomized, controlled trials (RCTs) of efficacy or effectiveness and for studies of any design which reported adverse events. Pooled estimates were calculated using a random effects model.Results -Eighty-seven RCTs fulfilled our inclusion criteria for efficacy or effectiveness and 42 studies examined safety or tolerability. Two head-to-head RCTs of type 2 diabetes demonstrated significant improvements in A1c in both groups at follow-up with no significant difference between groups; a third study found no significant change in A1c in either group. The pooled estimate of effect on A1c for pioglitazone compared to placebo was -0.99% (95% confidence interval [CI], -1.18, -0.81) and for rosiglitazone was -0.92% (95% CI, -1.2, -0.64). Indirect comparison revealed no significant difference in A1c (between-drug difference -0.07% [95% CI, -0.41, 0.27]). Rosiglitazone increased total cholesterol compared to pioglitazone (net between-drug effect 13.91 mg/dl [95% CI, 1.20 to 26.62]). Both drugs increased weight by 2 to 3 kg and rates of adverse events were similar for the two drugs. Data were insufficient to assess comparative effects on health outcomes such as cardiovascular events.Conclusions -Based largely on indirect evidence, the two thiazolidinediones appear to have similar effects on glycemic control and similar side-effect profiles. Rosiglitazone may increase total cholesterol compared to pioglitazone. Studies are needed which provide direct comparisons between the two drugs, particularly for long-term health outcomes.

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Section: Type 2 Diabetesmentioning

confidence: 54%

Comparative Effectiveness of Pioglitazone and Rosiglitazone in Type 2 Diabetes, Prediabetes,and the Metabolic Syndrome: A Meta-Analysis

Norris

Carson

Roberts

2007

CDR

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“…Their characterization provides novel scaffold information and a framework that may enable rational design of PAM with desired signal bias for GLP-1R. Low GLP-1 levels and decreased response to its treatment were found in some T2DM patients, − and β-arrestin 1/2 has been implicated in GLP-1R-mediated insulin secretion. , Therefore, the PAMs discovered here may offer a new therapeutic strategy to combat this deadly disease.…”

Section: Resultsmentioning

confidence: 89%

Allosteric Modulators Enhancing GLP-1 Binding to GLP-1R via a Transmembrane Site

et al. 2021

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The glucagon-like peptide-1 receptor (GLP-1R) is a well-established drug target for the treatment of type II diabetes. The development of small-molecule positive allosteric modulators (PAMs) of GLP-1R is a promising therapeutic strategy. Here, we report the discovery and characterization of PAMs with distinct chemotypes, binding to a cryptic pocket formed by the cytoplasmic half of TM3, TM5, and TM6. Molecular dynamic simulations and mutagenesis studies indicate that the PAM enlarges the orthosteric pocket to facilitate GLP-1 binding. Further signaling assays characterized their probe-dependent signaling profiles. Our findings provide mechanistic insights into fine-tuning GLP-1R via this allosteric pocket and open up new avenues to design small-molecule drugs for class B G-protein-coupled receptors.

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“…Low levels and a decreased response of GLP-1 have been observed in some type 2 patients. − Therefore, it will be of interest to determine whether compounds M_4 and M_9 can act as an allosteric modulator of GLP-1R and enhance the bioactivity of endogenous GLP-1. The activation of GLP-1R by M_4 (24.71 μM) in combination with different concentrations of GLP-1 (0.014–1450 nM) was studied by luciferase activity responding to cAMP production using HEK293-CREB cells transiently expressing human GLP-1R.…”

Section: Resultsmentioning

confidence: 99%

Structural Modeling and in Silico Screening of Potential Small-Molecule Allosteric Agonists of a Glucagon-like Peptide 1 Receptor

Redij

Chaudhari

et al. 2019

ACS Omega

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The glucagon-like peptide 1 receptor (GLP-1R) belongs to the pharmaceutically important class B family of G-protein-coupled receptors (GPCRs), and its incretin peptide ligand GLP-1 analogs are adopted drugs for the treatment of type 2 diabetes. Despite remarkable antidiabetic effects, GLP-1 peptide-based drugs are limited by the need of injection. On the other hand, developing nonpeptidic small-molecule drugs targeting GLP-1R remains elusive. Here, we first constructed a three-dimensional structure model of the transmembrane (TM) domain of human GLP-1R using homology modeling and conformational sampling techniques. Next, a potential allosteric binding site on the TM domain was predicted computationally. In silico screening of druglike compounds against this predicted allosteric site has identified nine compounds as potential GLP-1R agonists. The independent agonistic activity of two compounds was subsequently confirmed using a cAMP response element-based luciferase reporting system. One compound was also shown to stimulate insulin secretion through in vitro assay. In addition, this compound synergized with GLP-1 to activate human GLP-1R. These results demonstrated that allosteric regulation potentially exists in GLP-1R and can be exploited for developing small-molecule agonists. The success of this work will help pave the way for small-molecule drug discovery targeting other class B GPCRs through allosteric regulations.

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Comparison of Glycemic and Lipid Response to Pioglitazone Treatment in Mexican-Americans and Non-Hispanic Caucasians With Type 2 Diabetes

Cited by 8 publications

References 5 publications

Comparative Effectiveness of Pioglitazone and Rosiglitazone in Type 2 Diabetes, Prediabetes,and the Metabolic Syndrome: A Meta-Analysis

Comparative Effectiveness of Pioglitazone and Rosiglitazone in Type 2 Diabetes, Prediabetes,and the Metabolic Syndrome: A Meta-Analysis

Allosteric Modulators Enhancing GLP-1 Binding to GLP-1R via a Transmembrane Site

Structural Modeling and in Silico Screening of Potential Small-Molecule Allosteric Agonists of a Glucagon-like Peptide 1 Receptor

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