– Financing led by new investor Bain Capital Private Equity with participation from new and existing investors to support continued development of a differentiated, late-stage portfolio of obesity tre...

Glucagon-like peptide-1 (GLP-1) is a gut-derived hormone essential for maintaining glucose homeostasis through multiple physiological pathways: triggering insulin release, inhibiting glucagon secretion, delaying gastric emptying, enhancing feelings of fullness, and suppressing appetite. Since GLP-1 is prone to degradation by dipeptidyl peptidase 4, GLP-1 receptor agonists (GLP-1RAs) have been developed to surmount this degradation challenge. At present, GLP-1RAs have become highly effective treatments for managing type 2 diabetes mellitus and obesity. Beyond their well-established benefits for blood sugar regulation and weight control, GLP-1RAs also exhibit various biological activities associated with both insulinotropic effects and immunoregulation. These effects have been demonstrated through in vitro studies, preclinical models, and clinical observations. This review aims to explore the effects of GLP-1R signaling on various immune cells and evaluate the therapeutic potential of GLP-1RAs in autoimmune and autoinflammatory diseases, including psoriasis, inflammatory bowel diseases, rheumatoid arthritis, asthma, multiple sclerosis, Sjögren’s syndrome, and systemic lupus erythematosus.

While GLP1 injections have revolutionized treatment of diabetes and obesity, current approaches suffer from poor tolerability and high discontinuation. Goraltchouk and colleagues developed a gene ther...

An intrinsic hallmark of type 1 diabetes is the correlation between appearance of autoantibodies directed against islet cell autoantigens with subsequent d

The intrinsic pathways that control membrane organization in immune cells and their impact on cellular functions are poorly defined. We found that the nonvesicular cholesterol transporter Aster-A link...

In the context of parental or diet-induced obesity, preweaning ketosis contributes to improved health outcomes, particularly by regulating the histone acetylome and β-hydroxybutyrylome for transcriptional activation of beige fat biogenesis genes.

Acquisition adds potential first- and best-in-class asset, enhancing Novo Nordisk’s portfolio for treatment of MASH, one of the most prevalent obesity...

Yoni Freedhoff, MD, reviews the new book 'Food Intelligence,' which details the impact of food on nutrition, biochemistry, metabolism, and health.

AbstractBackground and Aims. Anti-obesity therapies co-targeting the glucose-dependent insulinotropic polypeptide (GIP) receptor achieve greater weight los

The SWEET project is a multicenter, randomized, controlled trial that shows that long-term consumption of sweeteners and sweetness enhancers improves body weight control and elicits beneficial gut microbiota changes in adults with overweight or obesity.

β-cell dysfunction and dedifferentiation towards an α-cell-like phenotype are hallmarks of type 2 diabetes. Her,e the authors detect five α-cell subpopulations, find differences between healthy and diabetic donors, and identify SMOC1 as an inducer of human β-cell dysfunction and dedifferentiation.

Nimacimab monotherapy did not meet its primary endpoint for weight loss; preliminary pharmacokinetic analysis showed lower than expected…...

Objective This study aimed to characterize the reasons for treatment discontinuation with injectable semaglutide or tirzepatide for obesity in regular clinical practice. Methods This cross-section...

Obesity and its related disorders, including type 2 diabetes and liver, kidney, and cardiovascular diseases, are now recognized as chronic inflammator…

Evidence is emerging that glucagon-like peptide-1 (GLP-1) receptor agonists have anti-inflammatory and chondroprotective properties independent of their effects on weight loss. In this Review, the authors discuss the potential effects of GLP-1 receptor agonists on the incidence, disease activity and progression of various forms of arthritis, as well as practical considerations for their use in this context.

This cohort study investigates the comparative risks of male external genital infections in adult male patients with type 2 diabetes treated with sodium-glucose cotransporter 2 (SGLT2) inhibitors vs g...

Diabetic kidney disease (DKD) is the leading cause of end-stage kidney failure. This study shows that prolonged glucagon exacerbates lipid accumulation, promoting renal injury in early DKD, rather than lipid oxidation. Targeting glucagon signaling significantly inhibits DKD progression.

Aims/hypothesis Genetic association studies have demonstrated that partial loss of SLC30A8 Function protects against type 2 diabetes in humans. We investigated the impact of complete loss of SLC30A8 Function on type 2 diabetes risk and related phenotypes in humans. Methods The Pakistan Genome Resource (PGR), a biobank comprising whole-exome and whole-genome sequences of 145,037 participants, was analysed for phenotypic associations with SLC30A8 loss-of-function (LoF) variants. To follow up on the observations in the PGR, we conducted recall-by-genotype analyses of SLC30A8 LoF heterozygotes and homozygotes, as well as their participating family members, using OGTTs. Results We identified 18 SLC30A8 knockouts, including homozygotes for a variant enriched in South Asians (Gln174Ter), and 1024 heterozygotes for LoF variants. Type 2 diabetes risk was lower in SLC30A8 LoF heterozygotes and homozygotes relative to non-carriers, and the protective effect strengthens in a gene dose-dependent manner (ORadditive=0.62; 95% CI 0.53, 0.72; p=1.1×10–9; ORrecessive=0.34; 95% CI 0.12, 0.93; p=0.04). OGTTs in recall-by-genotype studies showed a gene dose-dependent reduction in glucose levels, coupled with elevated insulin. Conclusions/interpretation The corrected insulin response, disposition index and insulin sensitivity index in LoF heterozygotes and homozygotes indicated higher glucose-stimulated insulin secretion with preserved beta cell function that was independent of BMI. These data suggest that therapeutic inhibition of SLC30A8, up to and including complete knockout, may treat type 2 diabetes safely and effectively. Graphical Abstract

Glucagon-like peptide-1 (GLP-1) supports beta cell health and function by potentiating glucose-dependent insulin production and secretion. While GLP-1…

Transparency in clinical research is essential for advancing medical knowledge, informing healthcare decisions, and maintaining public trust. The Food and Drug Administration Amendments Act (FDAAA) of...