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Background Glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) have emerged as promising therapeutic options for addressing Type‐2 diabetes, obesity, and related conditions. Among these, semaglutide, tirzepatide, liraglutide etc., all notable GLP‐1RA, have gained attention owing to their favourable pharmacological properties and clinical efficacy. Aims This comprehensive review aims to provide a detailed analysis of both the currently available GLP‐1RAs in the market and those undergoing clinical trials. The focus is on examining their mechanism of action, pharmacokinetics, efficacy in glycemic control and weight management, safety profile, and potential applications. Materials & Methods The review employs a systematic approach to gather information on GLP‐1RAs. Relevant literature from the currently literature and ongoing clinical trials is thoroughly examined. Detailed scrutiny is applied to understand the mechanism of action, pharmacokinetic properties, and clinical outcomes of these agents. Results The review presents a comprehensive overview of the GLP‐1RAs, highlighting their distinct mechanisms of action, pharmacokinetic profiles, and clinical effectiveness in glycemic control and weight management. Safety profiles are also discussed, providing a holistic understanding of these therapeutic agents. Discussion The findings are discussed in the context of advancements in the field of GLP‐1RAs. Potential applications beyond diabetes and obesity are explored, shedding light on the broader implications of these agents in managing related conditions. Conclusion In conclusion, this review underscores the significance of GLP‐1RAs, with a specific focus on semaglutide, in the management of type 2 diabetes, obesity, and beyond. By synthesizing information on their mechanisms, pharmacokinetics, efficacy, and safety, this review provides valuable insights into the potential benefits these agents offer, contributing to the ongoing discourse in the field. A picture showing how the AI‐driven translation is more relevant.

ABSTRACT Background Repurposing glucagon‐like peptide‐1 (GLP‐1) and GIP/GLP‐1 receptor agonists (RAs) for idiopathic intracranial hypertension (IIH) represents an attractive alternative to current treatments, supported by evidence of potent metabolic effects and reductions in cerebrospinal fluid secretion and intracranial pressure in vivo. Methods We evaluated the safety and efficacy of GLP‐1 RAs and GIP/GLP‐1 RAs in IIH. MEDLINE and Scopus databases were searched for randomized‐controlled trials (RCT), non‐randomized clinical trials, or registries in adults with IIH. Results Two clinical trials (one RCT and one non‐randomized case–control) and two registries, comprising 1550 IIH patients (768 receiving GLP‐1 or GIP/GLP‐1 RAs) were included. Compared with standard‐of‐care, GLP‐1 or GIP/GLP‐1 RAs were associated with a significantly lower risk of papilledema (RR: 0.25; 95% CI: 0.15–0.43; p < 0.01) and visual disturbances or blindness (RR: 0.41; 95% CI: 0.18–0.92; p = 0.03), and a near‐significant trend toward reduced headache risk (RR: 0.61; 95% CI: 0.34–1.07; p = 0.08). Additionally, GLP‐1 RAs significantly reduced monthly headache days at 3 months (MD = −3.64; 95% CI: −6.26 to −1.03; p < 0.01) and at the end of follow‐up (MD = −4.82; 95% CI: −8.80 to −0.85; p = 0.02). No association was detected between GLP‐1 RAs and body mass index. No serious adverse events or treatment discontinuations were reported; mild gastrointestinal adverse events and nausea occurred in 88% (95% CI: 0.46–1.00) of GLP‐1 RA‐treated patients. Conclusions GLP‐1 and dual GIP/GLP‐1 RAs are associated with a significantly lower risk of papilledema and visual disturbances or blindness and a lower headache risk compared with standard‐of‐care. Additionally, GLP‐1 RAs significantly reduce the monthly headache burden. Well‐designed RCTs are needed to robustly evaluate the effects of GLP‐1 and GIP/GLP‐1 RAs in IIH, which likely extend beyond their weight‐loss‐inducing properties. Trial Registration PROSPERO registration ID: CRD42025650082 GLP‐1 and dual GIP/GLP‐1 RAs are associated with a significantly lower risk of papilledema and visual disturbances or blindness and a lower headache risk compared with standard‐of‐care. Additionally, GLP‐1 RAs significantly reduce the monthly headache burden.

Highlights Despite the common practice of switching patients from one medicine to another—to improve efficacy, safety, or tolerability—guidance on how to do so is uncommon. During this time of global shortage of glucagon‐like peptide‐1 receptor agonist (GLP‐1 RA) ± glucose‐dependent insulinotropic polypeptide (GIP) RA therapies, this research letter offers a quick clinical reference of rough equivalency between GLP‐1 ± GIP RA for A1c and body weight reduction in people with type 2 diabetes.

PurposeWe report a case in which the use of semaglutide for weight loss was associated with delayed gastric emptying and intraoperative pulmonary aspiration of gastric contents.Clinical featuresA 42-yr-old patient with Barrett’s esophagus underwent repeat upper gastrointestinal endoscopy and ablation of dysplastic mucosa. Two months earlier, the patient had started weekly injections of semaglutide for weight loss. Despite having fasted for 18 hr, and differing from the findings of prior procedures, endoscopy revealed substantial gastric content, which was suctioned before endotracheal intubation. Food remains were removed from the trachea and bronchi using bronchoscopy. The patient was extubated four hours later and remained asymptomatic.ConclusionPatients using semaglutide and other glucagon-like peptide 1 agonists for weight management may require specific precautions during induction of anesthesia to prevent pulmonary aspiration of gastric contents.

ABSTRACT Background The cardioprotective effects of glucagon‐like peptide‐1 receptor agonist (GLP‐1RA)‐based therapies in nondiabetic individuals with overweight or obesity remain underexplored. This meta‐analysis evaluates their impact on cardiovascular events and metabolic parameters in this population. Methods A meta‐analysis was conducted using PubMed, Embase, Cochrane, and Web of Science databases from inception to June 18, 2024. Eligible studies were randomized controlled trials (RCTs) enrolling nondiabetic adults with overweight or obesity. These studies compared GLP‐1RA‐based therapies with placebo and reported cardiovascular events and metabolic parameters. Results A total of 29 RCTs involving 9 GLP‐1RA‐based drugs and 37 348 eligible participants were included. Compared to placebo, GLP‐1RA‐based therapies significantly reduced the risk of total cardiovascular events (relative risk: 0.81, 95% confidence interval [CI]: [0.76, 0.87]), major adverse cardiovascular events (0.80, [0.72, 0.89]), myocardial infarction (0.72, [0.61, 0.85]), and all‐cause mortality (0.81, [0.71, 0.93]). No significant differences were observed in cardiovascular death or stroke. Additionally, GLP‐1RA‐based therapies were associated with significant reductions in some cardiometabolic parameters. Among GLP‐1RA‐based therapies, orfroglipron demonstrated strong benefits in reducing systolic blood pressure (mean difference: −7.10 mmHg, 95% CI: [−11.00, −2.70]). Tirzepatide induced the greatest reduction in body mass index (−6.50 kg/m2, [−7.90, −5.10]) and hemoglobin A1c concentrations (−0.39%, [−0.52, −0.26]). Retatrutide and semaglutide were most effective in improving lipid profiles and reducing C‐reactive protein levels (−1.20 mg/dL, [−1.80, −0.63]), respectively. Conclusions In nondiabetic individuals with overweight or obesity, GLP‐1RA‐based therapies significantly reduce cardiovascular events and improve cardiometabolic parameters. These findings underscore the potential for individualized GLP‐1RA‐based therapies targeting cardiovascular risk factors.

Aims Multiple sclerosis (MS) still maintains increasing prevalence and poor prognosis, while glucagon‐like peptide‐1 receptor (GLP‐1R) agonists show excellent neuroprotective capacities recently. Thus, we aim to evaluate whether the GLP‐1R agonist liraglutide (Lira) could ameliorate central nervous system demyelination and inflammation. Methods The therapeutic effect of Lira was tested on experimental autoimmune encephalitis (EAE) in vivo and a microglia cell line BV2 in vitro. Results Lira administration could ameliorate the disease score of EAE mice, delay the disease onset, ameliorate pathological demyelination and inflammation score in lumbar spinal cord, reduce pathogenic T helper cell transcription in spleen, restore phosphorylated adenosine monophosphate‐activated protein kinase (pAMPK) level, autophagy level, and inhibit pyroptosis‐related NLR family, pyrin domain‐containing protein 3 (NLRP3) pathway in lumbar spinal cord. Additionally, cell viability test, lactate dehydrogenase release test, and dead/live cell staining test for BV2 cells showed Lira could not salvage BV2 from nigericin‐induced pyroptosis significantly. Conclusion Lira has anti‐inflammation and anti‐demyelination effect on EAE mice, and the protective effect of Lira in the EAE model may be related to regulation of pAMPK pathway, autophagy, and NLRP3 pathway. However, Lira treatment cannot significantly inhibit pyroptosis of BV2 cells in vitro. Our study provides Lira as a potential candidate for Multiple Sclerosis treatment. Liraglutide (Lira) has neuroprotective effect on experimental autoimmune encephalitis (EAE) mice, and the protective effect of Lira in the EAE model may be related to regulation of pAMPK level, autophagy, and NLRP3 pathway. However, Lira treatment cannot significantly inhibit pyroptosis of BV2 cells in vitro.

The 2023 update of the European Society of Cardiology guidelines for the management of cardiovascular disease (CVD) in patients with diabetes are designed to guide prevention, early diagnosis, and management of CVD in patients with diabetes and provide recommendations on CVD risk stratification, as well as on screening. This article provides a summary of the key recommendations and a practical approach for cardiologists in the Netherlands to implement these guidelines in daily clinical practice by focusing on recommendations related to type 2 diabetes, including a step-by-step scheme for prescription of Sodium-Glucose Transport Protein 2 Inhibitors (SGLT2) inhibitors and Glucagon-like peptide‑1 (GLP-1) receptor agonists. These agents can be prescribed in addition to standard care, and independent of glucose control, target HbA1c, or obesity.

Background Skeletal muscle atrophy is defined as a reduction of muscle mass caused by excessive protein degradation. However, the development of therapeutic interventions is still in an early stage. Although glucagon‐like peptide‐1 receptor (GLP‐1R) agonists, such as exendin‐4 (Ex‐4) and dulaglutide, are widely used for the treatment of diabetes, their effects on muscle pathology are unknown. In this study, we investigated the therapeutic potential of GLP‐1R agonist for muscle wasting and the mechanisms involved. Methods Mouse C2C12 myotubes were used to evaluate the in vitro effects of Ex‐4 in the presence or absence of dexamethasone (Dex) on the regulation of the expression of muscle atrophic factors and the underlying mechanisms using various pharmacological inhibitors. In addition, we investigated the in vivo therapeutic effect of Ex‐4 in a Dex‐induced mouse muscle atrophy model (20 mg/kg/day i.p.) followed by injection of Ex‐4 (100 ng/day i.p.) for 12 days and chronic kidney disease (CKD)‐induced muscle atrophy model. Furthermore, we evaluated the effect of a long‐acting GLP‐1R agonist by treatment of dulaglutide (1 mg/kg/week s.c.) for 3 weeks, in DBA/2J‐mdx mice, a Duchenne muscular dystrophy model. Results Ex‐4 suppressed the expression of myostatin (MSTN) and muscle atrophic factors such as F‐box only protein 32 (atrogin‐1) and muscle RING‐finger protein‐1 (MuRF‐1) in Dex‐treated C2C12 myotubes. The suppression effect was via protein kinase A and protein kinase B signalling pathways through GLP‐1R. In addition, Ex‐4 treatment inhibited glucocorticoid receptor (GR) translocation by up‐regulating the proteins of GR inhibitory complexes. In a Dex‐induced muscle atrophy model, Ex‐4 ameliorated muscle atrophy by suppressing muscle atrophic factors and enhancing myogenic factors (MyoG and MyoD), leading to increased muscle mass and function. In the CKD muscle atrophy model, Ex‐4 also increased muscle mass, myofiber size, and muscle function. In addition, treatment with a long‐acting GLP‐1R agonist, dulaglutide, recovered muscle mass and function in DBA/2J‐mdx mice. Conclusions GLP‐1R agonists ameliorate muscle wasting by suppressing MSTN and muscle atrophic factors and enhancing myogenic factors through GLP‐1R‐mediated signalling pathways. These novel findings suggest that activating GLP‐1R signalling may be useful for the treatment of atrophy‐related muscular diseases.

The GLP‐1 receptor (GLP‐1R) in the kidney is expressed exclusively in vascular smooth muscle cells in arteries and arterioles. Downstream effects of the activation of the renal vascular GLP‐1R are elusive but may involve regulation of the renin‐angiotensin‐aldosterone system (RAAS). The expression of Ren1 in the mouse renal vasculature was investigated by in situ hybridization after a single subcutaneous dose of liraglutide, semaglutide and after repeated injections of liraglutide. Single and repeated exposure to GLP‐1R agonists induced expression of Ren1 in the renal vascular smooth muscle cell compartment compared with vehicle injected controls (p < .0001) for both semaglutide and liraglutide. The present data show a robust induction of Ren1 expression in the vascular smooth muscle cells of the kidney after single and repeated GLP‐1R activation and this renin recruitment may be involved in the effects of GLP‐1R agonist treatment on kidney disease. Single and repeated injections with long acting GLP‐1R agonists leads to induction of Ren1 transcription from VSMC in renal vasculature in mice.

Obesity and its complications—including type 2 diabetes, cardiovascular disease, and certain cancers—constitute a rising global epidemic that has imposed a substantial burden on health and healthcare systems over the years. It is becoming increasingly clear that there is a link between obesity and the gut microbiota. Gut dysbiosis, characterized as microbial imbalance, has been consistently associated with obesity in both humans and animal models, and can be reversed with weight loss. Emerging evidence has shown that microbial-derived metabolites such as short-chain fatty acids (SCFAs)—including acetate, propionate, and butyrate—provide benefits to the host by impacting organs beyond the gut, including adipose tissue. In this review, we summarize what is currently known regarding the specific mechanisms that link gut-microbial-derived SCFAs with adipose tissue metabolism, such as adipogenesis, lipolysis, and inflammation. In addition, we explore indirect mechanisms by which SCFAs can modulate adipose tissue metabolism, such as via perturbation of gut hormones, as well as signaling to the brain and the liver. Understanding how the modulation of gut microbial metabolites such as SCFAs can impact adipose tissue function could lead to novel therapeutic strategies for the prevention and treatment of obesity.