Journal of Diabetes Investigation, Год журнала: 2024, Номер 15(9), С. 1177 - 1190
Опубликована: Июнь 14, 2024
Imeglimin is a recently approved oral antidiabetic agent that improves insulin resistance, and promotes secretion from pancreatic β-cells. Here, we investigated the effects of imeglimin on glucagon α-cells.
Язык: Английский
Hepatology, Год журнала: 2024, Номер unknown
Опубликована: Март 19, 2024
Metabolic dysfunction–associated steatotic liver disease, formerly known as NAFLD, has ascended to prominence the predominant chronic disease in Western countries and now stands a leading cause of transplantations. In more advanced stage, metabolic steatohepatitis (MASH) may lead fibrosis, gateway cirrhosis, cancer, failure. Despite extensive research exploration various drug mechanisms, anticipation for inaugural approved materialize by 2024 is palpable, marking significant milestone. Numerous pathways have been investigated MASH treatment, exploring thyroid hormone receptors, glucagon-like peptides 1, peroxisome proliferator–activated agents influencing hepatic steatosis synthesis, inflammatory pathways, genetic components, fibrosis an array other avenues. Over time, key regulatory directions crystallized, manifesting 2 primary endpoints under investigation: resolution without worsening and/or improvement stage steatohepatitis, especially used phase 3 clinical trials, while alternative noninvasive are explored trials. The prospect proving efficacy trials opens doors combination therapies, evaluating ideal drugs yield comprehensive benefits, extending beyond organs. Certain already underway. this review, we discuss forefront 2023/2024, illuminating outcomes, future trajectories. Furthermore, tackle challenges confronting propose potential strategies surmounting them.
Язык: Английский
Процитировано
19
Diabetes Obesity and Metabolism, Год журнала: 2022, Номер 25(4), С. 1011 - 1023
Опубликована: Дек. 17, 2022
Abstract Aim To report two phase I studies of the novel subcutaneous glucagon‐like peptide‐1 receptor/glucagon receptor (GLP‐1R/GCGR) dual agonist BI 456906 versus placebo in healthy volunteers and people with overweight/obesity. Materials Methods A Ia study (NCT03175211) investigated single rising doses (SRDs) 24 males a body mass index (BMI) 20–<30 kg/m 2 . Ib (NCT03591718) multiple (MRDs) (escalated over 6 [Part A] or 16 B] weeks) 125 adults BMI 27–40 Results In SRD (N = 24), mean weight decreased increasing dose. MRD study, maximum decreases placebo‐corrected were at week (–5.79%, dosage schedule [DS] 1; Part A) (–13.8%, DS7; B). reduced plasma amino acids glucagon, indicating target engagement GCGRs GLP‐1Rs. Drug‐related adverse events (AEs) increased The most frequent drug‐related AE SRDs was appetite (n 9, 50.0%), subjects (8.3%) did not complete trial because AEs (nausea vomiting). During 80), 10 (12.5%) discontinued 456906, commonly cardiac vascular 6, 7.5%); during B 45), eight (17.8%) mainly 13.3%), gastrointestinal disorders. Conclusions produced loss 13.8% (week 16), highlighting its potential to promote clinically meaningful
Язык: Английский
Процитировано
46
Molecules, Год журнала: 2023, Номер 28(7), С. 3094 - 3094
Опубликована: Март 30, 2023
Obesity and type 2 diabetes (T2DM) are major public health concerns associated with serious morbidity increased mortality. Both obesity T2DM strongly adiposopathy, a term that describes the pathophysiological changes of adipose tissue. In this review, we have highlighted tissue dysfunction as factor in etiology these conditions since it promotes chronic inflammation, dysregulated glucose homeostasis, impaired adipogenesis, leading to accumulation ectopic fat insulin resistance. This dysfunctional state can be effectively ameliorated by loss at least 15% body weight, is correlated better glycemic control, decreased likelihood cardiometabolic disease, an improvement overall quality life. Weight achieved through lifestyle modifications (healthy diet, regular physical activity) pharmacotherapy. summarized different effective management strategies address weight loss, such bariatric surgery several classes drugs, namely metformin, GLP-1 receptor agonists, amylin analogs, SGLT2 inhibitors. These drugs act targeting various mechanisms involved pathophysiology T2DM, they been shown induce significant improve control obese individuals T2DM.
Язык: Английский
Процитировано
36
Journal of Hepatology, Год журнала: 2024, Номер 81(5), С. 837 - 846
Опубликована: Июнь 8, 2024
Survodutide is a glucagon/glucagon-like peptide-1 receptor dual agonist in development for the treatment of metabolic dysfunction-associated steatohepatitis (MASH). We investigated pharmacokinetic and safety profile survodutide people with cirrhosis.
Язык: Английский
Процитировано
17
Peptides, Год журнала: 2024, Номер 173, С. 171149 - 171149
Опубликована: Янв. 5, 2024
Options for the treatment of type 2 diabetes mellitus (T2DM) and obesity have recently been expanded by results several large clinical trials with incretin-based peptide therapies. Most these studies conducted glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide, which is available as a once weekly subcutaneous injection daily tablet, injected dual tirzepatide, interacts receptors GLP-1 glucose-dependent insulinotropic polypeptide (GIP). In individuals T2DM therapies achieved reductions glycated haemoglobin (HbA1c) > 2% lowered body weight 10%. some studies, agents tested in non-diabetic, obese at much higher doses 15%. Emerging evidence suggests can also offer cardio-protective potentially reno-protective effects. Other early development, notably triple GLP-1/GIP/glucagon (retatrutide) combination semaglutide amylin analogue cagrilintide (CagriSema), shown strong efficacy. Although incretin incur adverse gastrointestinal effects are most patients mild-to-moderate transient but result cessation cases. Thus, efficacy new enhancing opportunity to control blood glucose improve obesity.
Язык: Английский
Процитировано
11
European Journal of Medicinal Chemistry, Год журнала: 2024, Номер 269, С. 116342 - 116342
Опубликована: Март 17, 2024
Язык: Английский
Процитировано
11
Diabetes Obesity and Metabolism, Год журнала: 2024, Номер unknown
Опубликована: Июнь 9, 2024
Abstract Type 2 diabetes mellitus (T2DM) is associated with obesity and, therefore, it important to target both overweight and hyperglycaemia. Glucagon plays roles in glucose, amino acid fat metabolism may also regulate appetite energy expenditure. These physiological properties are currently being exploited therapeutically several compounds, most often combination glucagon‐like peptide‐1 (GLP‐1) agonism the form of dual agonists. With this combination, increases hepatic glucose production hyperglycaemia, which would be counterproductive, largely avoided. In multiple randomized trials, co‐agonists have been demonstrated lead significant weight loss participants T2DM, even improved glycated haemoglobin (HbA1c) levels. addition, reductions content observed. Here, we review discuss studies so far available. Twenty‐six trials seven different GLP‐1 receptor (GLP‐1R)/glucagon (GCGR) were identified reviewed. GLP‐1R/GCGR generally provided loss, content, lipid profiles, insulin secretion sensitivity, some cases, HbA1c A higher incidence adverse effects was present co‐agonist treatment than agonist monotherapy or placebo. Possible additional risks glucagon discussed. delicate balance between seems particular importance. Further exploring optimal ratio activation dosage titration regimens needed ensure a sufficient safety profile while providing clinical benefits.
Язык: Английский
Процитировано
11
Expert Opinion on Pharmacotherapy, Год журнала: 2024, Номер 25(9), С. 1249 - 1263
Опубликована: Июнь 12, 2024
Metabolic dysfunction-associated steatotic liver disease (MASLD) is defined by hepatic steatosis and cardiometabolic risk factors like obesity, type 2 diabetes, dyslipidemia. Persistent metabolic injury may promote inflammatory processes resulting in steatohepatitis (MASH) fibrosis. Mechanistic insights helped to identify potential drug targets, thereby supporting the development of novel compounds modulating drivers.
Язык: Английский
Процитировано
10
International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(4), С. 1651 - 1651
Опубликована: Фев. 14, 2025
Obesity is closely related to metabolic diseases, which brings a heavy burden the health care system. It urgent formulate and implement effective treatment strategies. Glucagon-like peptide-1 (GLP-1) protein with seven transmembrane domains connected by type B G proteins, widely distributed expressed in many organs tissues. GLP-1 analogues can reduce weight, lower blood pressure, improve lipids. Obesity, diabetes, cardiovascular other diseases have caused scientists' research development boom. Among them, GLP-1R agonist drugs developed rapidly weight-loss drugs. In this paper, based on target of GLP-1, mechanism action obesity was deeply studied, approved designed for were elaborated detail. Innovatively put forward summarized double triple targeted better effects less toxic side effects, make full use multi-target methods treat future. Finally, it pointed out that intestinal flora microorganisms benefits obesity, fecal bacteria transplantation may be potential harm body. This article provides some promising strong practical value.
Язык: Английский
Процитировано
1
Diabetology & Metabolic Syndrome, Год журнала: 2025, Номер 17(1)
Опубликована: Фев. 17, 2025
Glucagon-like peptide-1 (GLP-1) is an incretin peptide hormone mainly secreted by enteroendocrine intestinal L-cells. GLP-1 also α-cells of the pancreas and central nervous system (CNS). secretion stimulated nutrient intake exerts its effects on glucose homeostasis stimulating insulin secretion, gastric emptying confiding food intake, β-cell proliferation. The insulinotropic GLP-1, reduction in type 2 diabetes mellitus (T2DM), have made attractive option for treatment T2DM. Furthermore, GLP-1-based medications such as receptor agonists dipeptidyl peptidase-4 inhibitors, been shown to improve control preclinical clinical trials with human subjects. Importantly, increasing endogenous production different mechanisms or number L-cells that tend produce this may be another effective therapeutic approach managing Herein, we briefly describe agents/compounds enhance function. Then, will discuss approaches can increase through various stimuli. Finally, introduce potential L-cell differentiation future alternative
Язык: Английский
Процитировано
1