GLP-1

Selective modification of peptides is often exploited to improve pharmaceutically relevant properties of bioactive peptides like stability, circulation time, and potency. In Nature, natural products belonging to the class of ribosomally synthesized and post-translationally modified peptides (RiPPs) are known to install a number of highly attractive modifications with high selectivity. These modifications are installed by enzymes guided to the peptide by corresponding leader peptides that are removed as the last step of biosynthesis...

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is strongly associated with type 2 diabetes mellitus (T2DM). Lifestyle intervention remains a preferred treatment modality for NAFLD. The glucagon-like peptide (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors have been developed as new glucose-lowering drugs, which can improve fatty liver via an insulin-independent glucose-lowering effect. However, studies exploring the efficacy of GLP-1 receptor agonists combined with SGLT-2 inhibitors in patients with NAFLD and T2DM are scanty...

The development of oligomeric glucagon-like peptide-1 (GLP-1) and GLP-1-containing coagonists holds promise for enhancing the therapeutic potential of the GLP-1-based drugs for treating type 2 diabetes mellitus (T2DM). Here, we report a facile, efficient, and customizable strategy based on genetically encoded SpyCatcher-SpyTag chemistry and an inducible, cleavable self-aggregating tag (icSAT) scheme. icSAT-tagged SpyTag-fused GLP-1 and the dimeric or trimeric SpyCatcher scaffold were designed for dimeric or trimeric GLP-1, while icSAT-tagged SpyCatcher-fused GLP-1 and the icSAT-tagged SpyTag-fused GIP were designed for dual GLP-1/GIP (glucose-dependent insulinotropic polypeptide) receptor agonist...

No abstract text is available yet for this article.

INTRODUCTION: Lymphedema is a major public health issue for many women undergoing breast cancer treatment. Although weight loss has been reported to be beneficial in the treatment of lymphedema, no studies to date have examined the use of GLP-1RAs for the treatment of secondary lymphedema. This case report describes a patient who experienced significant resolution of her breast cancer-related lymphedema after initiation of a GLP-1RA for weight loss. MAIN SYMPTOMS AND/OR IMPORTANT CLINICAL FINDINGS: Nine months postoperatively the patient developed arm swelling and disability...

AIM: Emerging anti-obesity pharmacotherapy provides an option to correct maladaptive physiological and hormonal changes associated with obesity. One of the widely used medications in this context is glucagon-like peptide 1 (GLP-1) agonists. However, the misuse of these medications without any guidance and monitoring of lifestyle modifications can lead to unfavorable outcomes. The study aims to evaluate the effectiveness of a hybrid care model, incorporating GLP-1 and GLP-1/GIP agonist therapies, in managing obese patients with/without pre-diabetes...

AIMS: To summarize the effects of semaglutide 2.4 mg on weight-related quality of life (WRQOL) and health-related quality of life (HRQOL), focusing on the confirmatory secondary endpoint of physical functioning. MATERIALS AND METHODS: The STEP 1-4 Phase 3a, 68-week, double-blind, randomized controlled trials assessed the efficacy and safety of semaglutide 2.4 mg versus placebo in individuals with overweight/obesity. WRQOL and HRQOL were assessed by change from baseline to Week 68 in two different but complementary measures, the Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite-CT; STEP 1 and 2) and the SF-36v2 Health Survey Acute (SF-36v2; STEP 1-4)...

AIM: To evaluate gastric emptying (GE) and the glycaemic response to a 75-g oral glucose load in newly diagnosed, treatment-naïve Han Chinese with type 2 diabetes (T2D) before insulin pump therapy, after 4 weeks of insulin pump therapy, and 12-15 months after insulin pump therapy. MATERIALS AND METHODS: Twenty participants with T2D (baseline glycated haemoglobin [± SD] 10.7% [± 1.2%] 93 [± 10] mmol/mol) ingested a 75-g glucose drink containing 150 mg 13 C-acetate, to determine the gastric half-emptying time, and underwent assessment of plasma glucose and serum insulin, C-peptide and glucagon-like peptide-1 (GLP-1) over 180 min before and after 4 weeks of insulin pump therapy (discontinued for 48 h before re-assessment)...

No abstract text is available yet for this article.

AIMS: To evaluate the determinants of cardiovascular (CV) protection in men and women treated with glucagon-like peptide-1 receptor agonists (GLP1-RA). METHODS: Retrospective cohort study of 550 patients (43% women), with and without established CV disease, followed at a single center after the first prescription of a GLP1-RA. We analyzed the determinants of major adverse cardiovascular events (MACE) in men and women. RESULTS: The rate of MACE was similar between sexes...

Type 2 diabetes mellitus (T2DM) significantly impairs the functionality and number of endothelial progenitor cells (EPCs) and resident endothelial cells, critical for vascular repair and regeneration, exacerbating the risk of vascular complications. GLP-1 receptor agonists, like dulaglutide, have emerged as promising therapeutic agents due to their multifaceted effects, including the enhancement of EPC activity and protection of endothelial cells. This study investigates dulaglutide's effects on peripheral blood levels of CD34+ and CD133+ cells in a mouse model of lower limb ischemia and its protective mechanisms against high-glucose-induced damage in endothelial cells...

BACKGROUND AND AIMS: Add-on of basal insulin (BI) to intensify the ongoing therapy with glucagon-like peptide 1 receptor agonist (GLP-1 RA) is recommended, but it is unclear if free or fixed combination of BI and GLP-1 RA produce similar outcomes. A retrospective comparative effectiveness analysis of the add-on of glargine 300 U/mL (Gla-300) to ongoing GLP-1 RA vs. switch to fixed ratio combination of degludec and liraglutide (iDegLira) was performed. METHODS AND RESULTS: Real-world data collected in electronic medical records by 32 Italian diabetes clinics...

BACKGROUND AND AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) promote weight loss by suppressing appetite, enhancing satiety, regulating glucose metabolism and delaying gastric motility. We sought to determine whether GLP-1 RA use could impact sedated medical procedures like esophagogastroduodenoscopy (EGD). METHODS: We conducted a retrospective study on 35,183 patients who underwent EGD between 2019 and 2023, 922 of which were using a GLP-1-RA. Data were collected regarding demographics, diabetes status, retained gastric contents during EGD (RGC), incidence of aborted EGD, and necessity for repeat EGD...

BACKGROUND AND AIMS: Studies have shown that hydrothermal duodenal mucosal ablation results in improved glycemic control. Re-Cellularization via Electroporation Therapy (ReCET) is a novel endoscopic procedure that uses electroporation to induce cellular apoptosis and subsequent reepithelization. In this study, we aimed to eliminate exogenous insulin treatment in T2D patients through a single ReCET procedure combined with a GLP-1 receptor agonist (GLP-1RA). Feasibility, safety, and (dose) efficacy of ReCET were assessed...

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is a leading cause of cancer death. HCC is preventable with about 70 percent of HCC attributable to modifiable risk factors. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), FDA-approved medications for treating type 2 diabetes mellitus (T2DM), have pleiotropic effects on counteracting risk factors for HCC. Here we evaluate the association of GLP-1RAs with incident HCC risk in a real-world population. METHODS: This retrospective cohort included 1,890,020 patients with a diagnosis of T2DM who were prescribed GLP-1RAs or other non-GLP-1RA anti-diabetes medications and had no prior diagnosis of HCC...

The G protein-coupled bile acid receptor 1 (GPBAR1) or TGR5 is widely distributed across organs, including the small intestine, stomach, liver, spleen, and gallbladder. Many studies have established strong correlations between TGR5 and glucose homeostasis, energy metabolism, immune-inflammatory responses, and gastrointestinal functions. These results indicate that TGR5 has a significant impact on the progression of tumor development and metabolic disorders such as diabetes mellitus and obesity. Targeting TGR5 represents an encouraging therapeutic approach for treating associated human ailments...

AIMS: Corticosteroids are the treatment of choice for many inflammatory diseases but often lead to adverse effects, including hyperglycaemia. This study investigated the mechanisms driving differential effects on glucose control for AZD9567, an oral nonsteroidal selective glucocorticoid receptor modulator vs. prednisolone in 46 patients with type 2 diabetes mellitus. METHODS: In this randomized, double-blind, 2-way cross-over study (NCT04556760), participants received either AZD9567 72 mg and prednisolone 40 mg daily (cohort 1); AZD9567 40 mg and prednisolone 20 mg daily (cohort 2); or placebo and prednisolone 5 mg daily (cohort 3)...

BACKGROUND: Obesity and overweight are a significant public health concern. Subcutaneous semaglutide 2.4 mg injection is a glucagon-like peptide-1 (GLP-1) analogue approved by the European Medicines Agency as an adjunct to a reduced calorie diet and increased physical activity (diet and exercise, D&E) for the treatment obesity and overweight in the presence of at least one weight related comorbidity. This study aimed to assess the cost-effectiveness of semaglutide 2.4 mg in combination with D&E compared to D&E alone for the Portuguese setting...

PURPOSE OF REVIEW: To review the current medical therapies available for treatment of obesity in children and adolescents less than 18 years old in the United States and outline the approach to their use. RECENT FINDINGS: Obesity is a chronic disease with increasing prevalence in children and adolescents in the United States. Over the past few years, more FDA-approved medical treatments for obesity, such as GLP-1 receptor agonists, have emerged for patients less than 18 years old...

Despite the risk of atherosclerosis has progressively declined over the past few decades, subjects with type 2 diabetes mellitus (T2DM) continue to experience substantial excess of atherosclerotic cardiovascular disease (ASCVD)-related events. Therefore, there is urgent need to treat ASCVD disease in T2DM earlier, more intensively, and with greater precision. Many factors concur to increase the risk of atherosclerosis, and multifactorial intervention remains the basis for effective prevention or reduction of atherosclerotic events...