LY3298176, A Novel Dual GIP And GLP-1 Receptor Agonist For The Treatment Of Type 2 Diabetes Mellitus: From Discovery To Clinical Proof Of Concept

ConclusionsBased on these results, the pharmacology of LY3298176 translates from preclinical to clinical studies. LY3298176 has the potential to deliver clinically meaningful improvement in glycaemic control and body weight. The data warrant further clinical evaluation of LY3298176 for the treatment of T2DM and potentially obesity.
Source: Molecular Metabolism - Category: Endocrinology Source Type: research

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In conclusion, patients with fragility vertebral fractures were predominantly female and tended to be overweight or obese, although male patients tended to have a lower BMI than female patients. PMID: 32238668 [PubMed - as supplied by publisher]
Source: Endocrine Journal - Category: Endocrinology Tags: Endocr J Source Type: research
Conclusions: GCP patients (otherwise systemically healthy) were characterized by increased Th17-proinflammatory cell phenotype positive for the IL-23 receptor in peripheral blood. The proportion of Th17 cells that are negative for the IL-23 receptor in the peripheral blood of systemically healthy patients seemed to be unaffected by the presence or absence of chronic periodontitis.
Source: Journal of Applied Oral Science - Category: Dentistry Source Type: research
In this study, we found that cofilin competes with tau for direct microtubule binding in vitro, in cells, and in vivo, which inhibits tau-induced microtubule assembly. Genetic reduction of cofilin mitigates tauopathy and synaptic defects in Tau-P301S mice and movement deficits in tau transgenic C. elegans. The pathogenic effects of cofilin are selectively mediated by activated cofilin, as active but not inactive cofilin selectively interacts with tubulin, destabilizes microtubules, and promotes tauopathy. These results therefore indicate that activated cofilin plays an essential intermediary role in neurotoxic signaling th...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Conclusions/interpretationMEDI4166 was associated with an acceptable tolerability profile and significantly decreased LDL-cholesterol levels in a dose-dependent manner in overweight or obese patients with type 2 diabetes. However, there were no significant reductions in postprandial glucose levels at any dose of MEDI4166.Trial registrationClinicalTrials.gov NCT02524782FundingThis study was funded by MedImmune LLC, Gaithersburg, MD, USA.
Source: Diabetologia - Category: Endocrinology Source Type: research
CONCLUSIONS: There is insufficient evidence to support the use of metformin for women with obesity in pregnancy for improving maternal and infant outcomes. Metformin was, however, associated with increased risk of adverse effects, particularly diarrhoea. The quality of the evidence in this review varied from high to low, with downgrading decisions based on study limitations and inconsistency.There were only a small number of studies included in this review. Furthermore, none of the included studies included women categorised as 'overweight' and no trials looked at metformin in combination with another treatment.Future rese...
Source: Cochrane Database of Systematic Reviews - Category: General Medicine Authors: Tags: Cochrane Database Syst Rev Source Type: research
ConclusionRegardless of age or renal function, the benefits of EQW relative to BI treatment are improved glycaemic control and increased weight loss, which should be weighed against the increased risk of gastrointestinal symptoms.
Source: Diabetes, Obesity and Metabolism - Category: Endocrinology Authors: Tags: ORIGINAL ARTICLE Source Type: research
ConclusionsDaily doses of RG7697 for 2 weeks were well tolerated by the majority of patients with T2D. Pharmacokinetic data supported once‐daily dosing and pharmacodynamic effect displayed dose‐dependent reductions in fasting and postprandial plasma glucose, without increasing the risk of hypoglycaemia.
Source: Diabetes, Obesity and Metabolism - Category: Endocrinology Authors: Tags: ORIGINAL ARTICLE Source Type: research
The QJM has recently published reviews of novel therapies in chronic airways disease.1 There is a potentially novel role for glucagon-like peptide 1 (GLP-1) agonists in obesity-related, metabolic asthma, though clinical trial data are lacking.2 On the basis of work with other inflammatory states, we hypothesised that clinically-indicated use of GLP-1 agonists for glycaemic control in type 2 diabetes mellitus (T2DM) would be safe in those with concomitant asthma, potentially leading to improved asthma control and fewer asthma exacerbations.3 In a pilot observational cohort study, we prospectively identified nine patients wi...
Source: QJM - Category: Internal Medicine Source Type: research
Abstract Metformin is the most widely prescribed drug for patients with type 2 diabetes mellitus and the first‐line pharmacologic option as supported by multiple international guidelines, yet a rather large proportion of patients cannot tolerate metformin in adequate amounts because of its associated gastrointestinal (GI) adverse events (AEs). GI AEs typically encountered with metformin therapy include diarrhoea, nausea, flatulence, indigestion, vomiting, and abdominal discomfort, with diarrhoea and nausea being the most common. Although starting at a low dose and titrating slowly may help prevent some of metformin's GI ...
Source: Diabetes, Obesity and Metabolism - Category: Endocrinology Authors: Tags: REVIEW ARTICLE Source Type: research
In conclusion, albiglutide has an acceptable GI tolerability profile, with nausea and vomiting rates slightly higher than that for placebo but lower than those for liraglutide.
Source: Diabetes, Obesity and Metabolism - Category: Endocrinology Authors: Tags: RESEARCH LETTER Source Type: research
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