Gut hormone-based pharmacology: novel formulations and future possibilities for metabolic disease therapy
AbstractGlucagon-like peptide-1 (GLP-1) receptor agonists are established pharmaceutical therapies for the treatment of type 2 diabetes and obesity. They mimic the action of GLP-1 to reduce glucose levels through stimulation of insulin secretion and inhibition of glucagon secretion. They also reduce body weight by inducing satiety through central actions. The GLP-1 receptor agonists used clinically are based on exendin-4 and native GLP-1 and are available as formulations for daily or weekly s.c. or oral administration. GLP-1 receptor agonism is also achieved by inhibitors of dipeptidyl peptidase-4 (DPP-4), which prevent th...
Source: Diabetologia - September 3, 2023 Category: Endocrinology Source Type: research
The future of incretins in the treatment of obesity and non-alcoholic fatty liver disease
AbstractIn the last few decades, glucagon-like peptide-1 receptor (GLP-1R) agonists have changed current guidelines and improved outcomes for individuals with type 2 diabetes. However, the dual glucose-dependent insulinotropic polypeptide receptor (GIPR)/GLP-1R agonist, tirzepatide, has demonstrated superior efficacy regarding improvements in HbA1c and body weight in people with type 2 diabetes. This has led to increasing scientific interest in incretin hormones and incretin interactions, and several compounds based on dual- and multi-agonists are now being investigated for the treatment of metabolic diseases. Herein, we h...
Source: Diabetologia - September 3, 2023 Category: Endocrinology Source Type: research
Incretins beyond type 2 diabetes
AbstractIncretin-based therapies, in particular glucagon-like peptide-1 (GLP-1) receptor agonists, have been evaluated in other forms of diabetes, but randomised controlled trials are mainly limited to people living with type 1 diabetes. In this review we present the evidence issuing from these trials and discuss their clinical implications as well as the difficulties in interpreting the data. In type 1 diabetes, the addition of GLP-1 receptor agonists to intensive insulin therapy lowers weight and required insulin doses compared with placebo, but the effects on glucose control (HbA1c, risk of hypoglycaemia) are dependent ...
Source: Diabetologia - September 3, 2023 Category: Endocrinology Source Type: research
SGLT2i and GLP-1 RA therapy in type 1 diabetes and reno-vascular outcomes: a real-world study
Conclusions/interpretationBoth SGLT2is and GLP-1 RAs have potential benefits as adjunctive agents in type 1 diabetes. SGLT2is provide cardio-renal benefits, despite an increase in the risk of DKA and urinary tract infection compared with GLP-1 RA therapy. Long-term evaluation of the efficacy and safety of these adjunctive therapies is required to guide their use in individuals with type 1 diabetes.Graphical Abstract (Source: Diabetologia)
Source: Diabetologia - September 3, 2023 Category: Endocrinology Source Type: research
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(Source: Diabetologia)
Source: Diabetologia - September 3, 2023 Category: Endocrinology Source Type: research
Metformin for the prevention of diabetes among people with HIV and either impaired fasting glucose or impaired glucose tolerance (prediabetes) in Tanzania: a Phase II randomised placebo-controlled trial
Conclusions/interpretationBlood glucose decreased over time in both the metformin and placebo arms during the trial but did not differ significantly between the arms at 12 months of follow up. Metformin therapy was found to be safe for use in individuals with HIV and prediabetes. A larger trial with longer follow up is needed to establish if metformin can be safely used for the prevention of diabetes in people who have HIV.Trial registrationThe trial is registered on the International Standard Randomised Controlled Trial Number (ISRCTN) registry (www.isrctn.com/), registration number: ISCRTN76157257.FundingThis research wa...
Source: Diabetologia - September 1, 2023 Category: Endocrinology Source Type: research
Incretin hormones and type 2 diabetes
AbstractIncretin hormones (glucose-dependent insulinotropic polypeptide [GIP] and glucagon-like peptide-1 [GLP-1]) play a role in the pathophysiology of type 2 diabetes. Along with their derivatives they have shown therapeutic success in type 2 diabetes, with the potential for further improvements in glycaemic, cardiorenal and body weight-related outcomes. In type 2 diabetes, the incretin effect (greater insulin secretory response after oral glucose than with ‘isoglycaemic’ i.v. glucose, i.e. with an identical glycaemic stimulus) is markedly reduced or absent. This appears to be because of a reduced ability of GIP to s...
Source: Diabetologia - September 1, 2023 Category: Endocrinology Source Type: research
Strength training is more effective than aerobic exercise for improving glycaemic control and body composition in people with normal-weight type 2 diabetes: a randomised controlled trial
Conclusions/interpretationIn normal-weight type 2 diabetes, strength training was superior to aerobic training alone, while no significant difference was observed between strength training and combination training for HbA1c reduction. Increased lean mass relative to decreased fat mass was an independent predictor of reduction in HbA1c level.Trial registrationClinicalTrials.gov NCT02448498.FundingThis study was funded by the National Institutes of Health (NIH; R01DK081371).Graphical Abstract (Source: Diabetologia)
Source: Diabetologia - September 1, 2023 Category: Endocrinology Source Type: research
The expanding incretin universe: from basic biology to clinical translation
AbstractIncretin hormones, principally glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1(GLP-1), potentiate meal-stimulated insulin secretion through direct (GIP + GLP-1) and indirect (GLP-1) actions on islet β-cells. GIP and GLP-1 also regulate glucagon secretion, through direct and indirect pathways. The incretin hormone receptors (GIPR and GLP-1R) are widely distributed beyond the pancreas, principally in the brain, cardiovascular and immune systems, gut and kidney, consistent with a broad array of e xtrapancreatic incretin actions. Notably, the glucoregulatory and anorectic activities of G...
Source: Diabetologia - September 1, 2023 Category: Endocrinology Source Type: research
Reversal of dual epigenetic repression of non-canonical Wnt-5a normalises diabetic corneal epithelial wound healing and stem cells
Conclusions/interpretationWe provide the first account of epigenetic changes in diabetic corneas including dual inhibition ofWNT5A by DNA methylation and miRNA action. Overall, Wnt-5a is a new corneal epithelial wound healing stimulator that can be targeted to improve wound healing and stem cells in the diabetic cornea.Data availabilityThe DNA methylation dataset is available from the public GEO repository under accession no. GSE229328 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE229328).Graphical Abstract (Source: Diabetologia)
Source: Diabetologia - September 1, 2023 Category: Endocrinology Source Type: research
Hyperglucagonaemia in diabetes: altered amino acid metabolism triggers mTORC1 activation, which drives glucagon production
Conclusions/interpretationAlpha cell exposure to hyperglycaemia enhances amino acid synthesis and transport, resulting in sustained activation of mTORC1, thereby increasing glucagon secretion. mTORC1 therefore plays a major role in mediating alpha cell dysfunction in diabetes.Data availabilityAll sequencing data are available from the Gene Expression Omnibus (GEO) repository (accession no. GSE154126;https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE154126)Graphical Abstract (Source: Diabetologia)
Source: Diabetologia - September 1, 2023 Category: Endocrinology Source Type: research
Socioeconomic aspects of incretin-based therapy
AbstractIncretin-based therapies, particularly glucagon-like peptide-1 receptor agonists (GLP-1 RAs), have demonstrated cardiovascular benefits in people with type 2 diabetes. However, socioeconomic disparities in their uptake may constrain the collective advantages offered by these medications to the broader population. In this review we examine the socioeconomic disparities in the utilisation of incretin-based therapies and discuss strategies to address these inequalities. Based on real-world evidence, the uptake of GLP-1 RAs is reduced in people who live in socioeconomically disadvantaged areas, have low income and educ...
Source: Diabetologia - September 1, 2023 Category: Endocrinology Source Type: research
Glycaemic control, risk of hypoglycaemia and all-cause mortality in new users of second-generation basal insulin with type 2 diabetes and chronic kidney disease: a nationwide register-based cohort study
Conclusions/interpretationWe found no difference in HbA1c reduction, hospitalisation for hypoglycaemia or all-cause mortality between Gla-300 and Deg-100 in a real-world population of new users with type 2 diabetes and moderate to end-stage chronic kidney disease. Therefore, we conclude that these two treatment options are equally effective and safe in this vulnerable population.Graphical Abstract (Source: Diabetologia)
Source: Diabetologia - September 1, 2023 Category: Endocrinology Source Type: research
Genetic associations vary across the spectrum of fasting serum insulin: results from the European IDEFICS/I.Family children ’s cohort
Conclusions/interpretationThe above results support the notion of a shared genetic architecture for dementia and metabolic traits. Our approach identified genetic variants that were associated with the tails of the insulin spectrum only. Because traditional heritability estimates assume that genetic effects are constant throughout the phenotype distribution, the new findings may have implications for understanding the discrepancy in heritability estimates from GWA and family studies and for the study of U-shaped biomarker –disease associations.Graphical Abstract (Source: Diabetologia)
Source: Diabetologia - September 1, 2023 Category: Endocrinology Source Type: research
Gut hormone-based pharmacology: novel formulations and future possibilities for metabolic disease therapy
AbstractGlucagon-like peptide-1 (GLP-1) receptor agonists are established pharmaceutical therapies for the treatment of type 2 diabetes and obesity. They mimic the action of GLP-1 to reduce glucose levels through stimulation of insulin secretion and inhibition of glucagon secretion. They also reduce body weight by inducing satiety through central actions. The GLP-1 receptor agonists used clinically are based on exendin-4 and native GLP-1 and are available as formulations for daily or weekly s.c. or oral administration. GLP-1 receptor agonism is also achieved by inhibitors of dipeptidyl peptidase-4 (DPP-4), which prevent th...
Source: Diabetologia - September 1, 2023 Category: Endocrinology Source Type: research
