GLP-1 analogs

Diabetes mellitus (DM) is a chronic metabolic disorder affecting millions of people worldwide, characterized by dysregulated glucose homeostasis and hyperglycemia. Diabetic retinopathy (DR) is one of the serious multisystemic complications. Aging is an important risk factor for DR. Endothelial sirtuin 1 (SIRT1) plays an important role in regulating the pathophysiology of glucose metabolism, cellular senescence, and aging. Liraglutide, an analog of Glucagon-like peptide 1 (GLP-1), has been widely used in the treatment of DM...

The primary treatment for autoimmune Diabetes Mellitus (Type 1 Diabetes Mellitus-T1DM) is insulin therapy. Unfortunately, a multitude of clinical cases has demonstrated that the use of insulin as a sole therapeutic intervention fails to address all issues comprehensively. Therefore, non-insulin adjunct treatment has been investigated and shown successful results in clinical trials. Various hypoglycemia-inducing drugs such as Metformin, glucagon-like peptide 1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, amylin analogs, and Sodium-Glucose Cotransporters 2 (SGLT-2) inhibitors, developed good outcomes in patients with T1DM...

The basic principle for the treatment of idiopathic diarrhoea (functional diarrhoea K59.1) is to delay transit through the gut in order to promote the absorption of electrolytes and water. Under mild conditions, bulking agents may suffice. With increasing severity, antidiarrhoeal pharmaceuticals may be added in a stepwise manner. In diarrhoea of unknown aetiology, peripherally-acting opioid receptor agonists, such as loperamide, are first-line treatment and forms the pharmaceutical basis of antidiarrheal treatment...

Late chronotype (LC) is related to obesity and altered food intake throughout the day. But whether appetite perception and gut hormones differ among chronotypes is unclear. Thus, we examined if early chronotype (EC) have different appetite responses in relation to food intake than LC. Adults with obesity were categorized using the Morningness-Eveningness Questionnaire (MEQ) as either EC ( n  = 21, 18F, MEQ = 63.9 ± 1.0, 53.7 ± 1.2 yr, 36...

Ipomoea batatas L. (IBL) has gained significant popularity as a complementary therapy or herbal medicine in the treatment of anti-diabetes. This review seeks to explore the mechanism by which flavonoid compounds derived from IBL exert their anti-diabetic effects through the activation of GLP-1. The review article refers to the PRISMA guidelines. In order to carry out the literature search, electronic databases such as Science Direct, Crossref, Scopus, and Pubmed were utilized. The search query was based on specific keywords, including Ipomoea batatas OR sweet potato AND anti-diabetic OR hypoglycemic...

Glucagon-like peptide 1 (GLP-1), a gastrointestinal peptide and central mediator of glucose metabolism, is secreted by L cells in the intestine in response to food intake. Postprandial secretion of GLP-1 is triggered by nutrient-sensing via transporters and G-protein-coupled receptors (GPCRs). GLP-1 secretion may be lower in adults with obesity/overweight (OW) or type 2 diabetes mellitus (T2DM) than in those with normal glucose tolerance (NGT), but these findings are inconsistent. Because of the actions of GLP-1 on stimulating insulin secretion and promoting weight loss, GLP-1 and its analogs are used in pharmacologic preparations for the treatment of T2DM...

Semaglutide is the first oral glucagon-like peptide-1 (GLP-1) analog commercially available for the treatment of type 2 diabetes. In this work, semaglutide was incorporated into poly(lactic-co-glycolic acid)-poly(ethylene glycol) (PLGA-PEG) nanoparticles (NPs) to improve its delivery across the intestinal barrier. The nanocarriers were surface-decorated with either a peptide or an affibody that target the human neonatal Fc receptor (hFcRn), located on the luminal cell surface of the enterocytes. Both ligands were successfully conjugated with the PLGA-PEG via maleimide-thiol chemistry and thereafter, the functionalized polymers were used to produce semaglutide-loaded NPs...

Heart failure is a clinical condition in which the heart is unable to maintain adequate cardiac output. Liraglutide is a glucagon-like peptide 1 (GLP-1) analogue that is used for the treatment of type 2 diabetes mellitus, but recent evidence suggests that it might have a beneficial role in treating heart failure. We conducted a review of existing literature and found five relevant studies. Data from these studies were extracted and then extrapolated into results following analysis. Four of the five studies found an increase in heart rate in heart failure patients...

Obesity is a chronic, recurring, progressive disease and a major public health problem associated with several other diseases that lead to disability, morbidity, and mortality. The prevalence of obesity has increased at pandemic levels, along with increasing weight-related comorbidities and deaths worldwide. Lifestyle interventions alone provide clinically significant long-term weight loss in only a small proportion of individuals, and bariatric surgery is not suitable or desirable for all patients. Historically, anti-obesity medications achieved a mean efficacy with weight loss between 5 and 10%, which significantly impacted several comorbidities and risk factors, but the average efficacy of these medications remained lower than that expected by both patients and health care professionals and eventually curbed long-term use...

OBJECTIVE: To review clinical trial data for incretin therapies that are approved or in late-stage development for overweight or obesity management, along with clinical implications of these therapies and future directions. METHODS: We searched for clinical trials involving incretin therapies studied specifically for overweight or obesity management in ClinicalTrials.gov and PubMed from registry inception through December 2023. RESULTS: Glucagon-like peptide-1 (GLP-1) receptor agonism, alone and in combination with glucose-dependent insulinotropic polypeptide (GIP) receptor agonism or glucagon agonism, leads to significant weight reduction in people with overweight or obesity...

BACKGROUND: Fibroblast growth factor 21 (FGF21) is a metabolic, endocrine hormone regulating insulin sensitivity, energy expenditure, and lipid metabolism. It has significant potential as a therapeutic drug for treating type 2 diabetes and obesity. However, the clinical efficacy of FGF21 analogs is limited due to their instability and short half-life. Glucagon-like peptide 1 (GLP-1) receptor agonists have been recognized as effective medications for type 2 diabetes mellitus and obesity over the past two decades...

PURPOSE: Many individuals search for obesity treatment options on the Internet. We aimed to analyze the popularity of pharmacological and surgical obesity treatment methods searched by Google users. MATERIAL AND METHODS: We used Google Trends to identify topics representing the following: recommended surgical methods (n = 9), recommended pharmacological methods (n = 10), and not recommended pharmacological methods (n = 34)...

Diabetic kidney disease (DKD) is a growing epidemic worldwide and a leading cause of end-stage kidney disease. Mineralocorticoid receptor (MR) blockade using Finerenone is a recently approved therapeutic approach to slow down the progression of DKD in patients with type 2 diabetes in addition to other therapies such as angiotensin-II converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), sodium-glucose co-transporter 2 (SGLT2) inhibitors, and glucagon-like peptide 1 (GLP-1) analogs. This review elaborates on the pathophysiologic pathways activated by aldosterone (the human mineralocorticoid) in DKD, the pharmacology of three different generations of mineralocorticoid receptor antagonists (MRAs), specifically, spironolactone, eplerenone, and finerenone, and the mechanisms by which these MRAs elicit their protective effects on the kidney under diabetic settings...

Gut-liver-brain axis is a three-way highway of information interaction system among the gastrointestinal tract, liver, and nervous systems. In the past few decades, breakthrough progress has been made in the gut liver brain axis, mainly through understanding its formation mechanism and increasing treatment strategies. In this review, we discuss various complex networks including barrier permeability, gut hormones, gut microbial metabolites, vagus nerve, neurotransmitters, immunity, brain toxic metabolites, β-amyloid (Aβ) metabolism, and epigenetic regulation in the gut-liver-brain axis...

Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of the metabolic syndrome, posing risks to cardiovascular and hepatic health worldwide. Non-alcoholic steatohepatitis (NASH) which is a severe form of NAFLD, has a global prevalence. Therapeutic targets for NASH include THR-β, GLP-1 receptor, PPARα/δ/γ, FGF21 analogs, and FXR, a bile acid nuclear receptor pivotal for regulating bile acid synthesis and excretion. Our study aims to design the non-steroidal FXR agonist for NASH treatment, as FXR's role in the regulation of bile acid processes, rendering it a promising drug target for NASH therapy...

Postprandial hyperinsulinemic hypoglycemia, although rare, is a well-documented complication that can manifest after upper gastrointestinal surgery. Despite its potential for severe morbidity, the underlying pathogenesis and optimal treatment strategies for this condition remain insufficiently understood. This report presents a compelling case of postprandial hypoglycemia following Billroth-II gastrojejunostomy, characterized by a marked increase in postprandial insulin levels, accompanied by the exaggerated response of incretin hormones...

OBJECTIVE: To evaluate the effect of common weight loss pharmacotherapies among low-income, racially diverse adult patients at an urban safety-net weight management clinic. METHODS: Our retrospective review from 2015 to 2019 examined patients who took either GLP-1 analog (GL) or phentermine/topiramate (PT) for ≥90 days and patients who exclusively pursued non-pharmacologic treatment for comparison. Changes in weight, blood pressure, and hemoglobin A1c at 1-year follow-up were reported...

BACKGROUND: GLP-1 receptor agonists (GLP-1RA) are increasingly used to treat adolescent obesity. However, the effect on endogenous GLP-1 secretory patterns following treatment in adolescents is unknown. The GLP-1RA exenatide was shown to significantly lower BMI and 2-hour glucose in adolescents with obesity, in the placebo-controlled, randomized controlled trial Combat-JUDO. The aim of this study was to evaluate effects of weekly injections of 2 mg exenatide extended release on secretory patterns of endogenous hormones during OGTT...

Alzheimer's is a prevalent, progressive neurodegenerative disease marked by cognitive decline and memory loss. The disease's development involves various pathomechanisms, including amyloid-beta accumulation, neurofibrillary tangles, oxidative stress, inflammation, and mitochondrial dysfunction. Recent research suggests that antidiabetic drugs may enhance neuronal survival and cognitive function in diabetes. Given the well-documented correlation between diabetes and Alzheimer's disease and the potential shared mechanisms, this review aimed to comprehensively assess the potential of new-generation anti-diabetic drugs, such as GLP-1 analogs, SGLT-2 inhibitors, and DPP-4 inhibitors, as promising therapeutic approaches for Alzheimer's disease...

OBJECTIVE: Binge eating disorder (BED) is the most common eating disorder, and yet only one pharmacotherapy (lisdexamfetamine), which has known abuse-potential, is FDA-approved. Topiramate is also commonly prescribed off-label for binge eating but has many contraindications. In contrast, the glucagon-like peptide-1 (GLP1) analog semaglutide has profound effects on central satiety signaling leading to reduced food intake, and has been approved for the treatment of obesity based on its efficacy and safety profile...