GLP-1 receptor agonists in diabetes and weight loss: the double-edged sword of innovation and risks

Frontiers in Clinical Diabetes and Healthcare, Год журнала: 2025, Номер 5

Опубликована: Янв. 9, 2025

In recent years, glucagon-like peptide-1 (GLP-1) receptor agonists have gained widespread popularity not only as effective agents in the management of type 2 diabetes but also for their beneficial impact on weight loss. Additionally, this surge interest has been underpinned by pleiotropic effects and spurred further investigation into potential applications beyond care. However, expanding adoption GLP-1 brings with it a set challenges complications. With promising therapeutic comes an increased scrutiny side effects.GLP-1 mimic action native peptide, enhancing insulin secretion, suppressing glucagon release, slowing gastric emptying, increasing satiety. Initially introduced to treat diabetes, they were found important effect loss; paradigm shift medical obesity may -in fact -be imminent, per opinion non-medical pundits [1][2][3]. Drugs like semaglutide, liraglutide or tirzepatide (a dual GIP analog) led significant reduction participants clinical trials real-world settings, making them popular patients physicians alike.The success lies multifaceted mechanisms, which address complex physiological pathways hunger, satiety, glucose metabolism. These drugs target pancreas gut brain's hypothalamic appetite-regulating centers. Some analogs be attributed actions central nervous system neurotransmitter secretion/action; enhance gamma-aminobutyric acid (GABA) activity, restore dopaminergic activity act parallel peptide YY (PYY) [4][5][6]. sense, are redefining approach metabolic disease addressing glycemic control influencing body cardiovascular health. Currently, long-term consequences analog use over 1.5 -2 years look promising; published meta-analyses, reduced morbidity mortality noted, whereas no appearance gastrointestinal neoplasia observed [7][8].The foster ongoing research new indications.Evidence suggests these benefits, studies indicating risk among people who [9][10][11][12]. explored GLP-1[3] liver health, including benefit treatment dysfunction associated fatty (MASLD) [13][14]. The anti-inflammatory neuroprotective properties being investigated, implications neurodegenerative conditions Alzheimer's [15][16][17]. Such raises possibility broader agonists, influence extends traditional management.As exciting advancements are, raise critical questions about society's preference pharmacological solutions lifestyle interventions diet exercise. mindset many practitioners, allure weight-loss medications indeed outweigh need changes, despite evidence that physical fundamental components sustainable Surveys internet worldwide indicated frank increase searches [18][19]. revealed more interested pharmaceutical loss than modifications. This trend is fueled relative ease accessibility medications, coupled perception can yield rapid, visible results (traditional social media statements "celebrities" add trend).Pharmaceutical companies responded demand pipeline drugs, based mechanisms agonists. focus pharmacotherapy, however, risks overshadowing essential role nonpharmacological chronic prevention management. It healthcare providers emphasize while play valuable plans, substitutes balanced diet, regular other modifications.While largely considered safe, usage drawn attention rare adverse events. Nonarteritic anterior ischemic optic neuropathy (NAION), idiopathic injury nerve head, marked sudden, painless vision eye swelling disc, reported association agonists' use, though such cases remain [20]. might trigger NAION yet fully understood, necessary determine whether causal [4] relationship exists. practice, experiencing visual disturbances therapy should evaluated promptly, consideration given discontinuing medication if link suspected.Pancreatitis known Although absolute low, pancreatitis severe even life-threatening. receptors expressed pancreas, researchers hypothesize pancreatic function ways could predispose certain individuals inflammation. Studies yielded mixed negative [21-23], there definitive linking higher incidence pancreatitis, remains listed effect.Other events, possibly linked analogs, include muscle mass loss, dermatological/hypersensitivity reactions, heart rate, left ventricular ejection fraction depressionThe emergence safety concerns reinforces importance individualized patient assessment before prescribing particularly those history disorders factors. Healthcare must engage thorough discussions patients, weighing benefits against ensuring understand signs symptoms events.The advent represents milestone obesity, presents challenge balancing drive innovation safety. landscape, devoid risks, detract from comprehensive, While offer much promise, underscore reality pharmacotherapy alone cannot root causes diseases. As we move forward, will crucial develop nuanced prescription drugs. Educating modification, well essential. needed clarify underlying events identify at [27].[5] transformed landscape management, offering extend control.However, reliance reflects societal de-emphasizing exercise managing although rare, serves reminder complexities drug careful selection monitoring. our pursuit advancements, innovative pharmacotherapies commitment safe responsible practice. providers, responsibility embrace tools modern medicine provides vigilant safeguarding health through informed, evidence-based promise undeniable, so caution judicious quest improve outcomes.

Язык: Английский

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Research progress of GLP-1RAs in the treatment of type 2 diabetes mellitus

Frontiers in Pharmacology, Год журнала: 2025, Номер 15

Опубликована: Янв. 20, 2025

Glucagon-like peptide-1 (GLP-1) is a 30-amino acid intestinal insulin-stimulating factor, which mainly secreted by L cells in the distal ileum and colon. It has various physiological functions, such as promoting insulin secretion synthesis, stimulating β-cell proliferation, inducing islet regeneration, inhibiting apoptosis glucagon release, delaying gastric emptying controlling appetite, etc. plays role through specific GLP-1 receptor (GLP-1R) distributed many organs or tissues participates regulation of glucose homeostasis body. agonists (GLP-1RAs) similar function GLP-1. Because its structural difference from natural GLP-1, it not easy to be degraded dipeptidyl peptidase-4 (DPP-4), thus prolonging action time. GLP-1RAs have been recognized new type hypoglycemic drugs widely used treatment 2 diabetes mellitus (T2DM). Compared with other non-insulin drugs, can only effectively reduce blood glycosylated hemoglobin (HbA1c), but also protect cardiovascular system, nervous system kidney without causing hypoglycemia weight gain. Therefore, good application prospects potential for further development.

Язык: Английский

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A Brief Review of Incretin Mimetics Intended for the Management of Diabetes and Associated Comorbidities

Опубликована: Май 21, 2024

Abstract Incretin mimetics, also known as glucagon-like peptide-1 (GLP-1) receptor agonists, are a class of medications used to treat type 2 diabetes by mimicking the actions incretin hormones in body. These responsible for promoting insulin release from pancreas response nutrient intake, well decreasing glucagon secretion, slowing gastric emptying, and satiety. By imitating these actions, mimetics help regulate blood sugar levels individuals with glucose intolerance. One key benefits is its ability lower without causing hypoglycemia. This especially important who may experience dangerous drops when using other medications. Additionally, have been shown promote weight loss some individuals, making them valuable option those struggling obesity addition diabetes. administered injection, once or twice daily, depending on specific medication. They often combined medications, such metformin insulin, optimal control. generally well-tolerated, common side effects including nausea, vomiting, diarrhea, which usually diminish over time body adjusts Studies that can improve cardiovascular outcomes diabetes, reducing risk heart attacks strokes. particularly significant given increased disease preserve pancreatic beta-cell function, producing insulin. slow progression reduce need higher doses time. Despite their many benefits, not limitations. be expensive compared make less accessible individuals. there concerns about potential pancreatitis cancer associated use However, more research needed fully understand risks. It healthcare providers carefully assess each individual's unique needs medical history considering mimetics. appropriate everyone, cancer. Patients should educated medications' proper administration ensure safety efficacy. Overall, emerged an therapeutic offering mechanism action control, loss, risk. With ongoing development this field, continue show promise tools managing complications comorbidities.

Язык: Английский

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Evolution and therapeutic potential of glucagon-like peptide 2 analogs

Biochemical Pharmacology, Год журнала: 2025, Номер 233, С. 116758 - 116758

Опубликована: Янв. 20, 2025

Язык: Английский

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Role of Plant-Derived Protein Hydrolysates and Peptides in Appetite Regulation

Trends in Food Science & Technology, Год журнала: 2025, Номер unknown, С. 104976 - 104976

Опубликована: Март 1, 2025

Язык: Английский

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Expanding the Reach of Sustainable Solid-Phase Peptide Synthesis: One-Pot, Metal-Free Alloc Removal–Peptide Coupling

Organic Letters, Год журнала: 2025, Номер unknown

Опубликована: Март 17, 2025

While the allyloxycarbonyl (Alloc) protecting group has played a key role in solid-phase peptide synthesis (SPPS), providing access to wide range of peptides, its removal suffered from relying on air-sensitive Pd(0) complexes hazardous solvents. We report metal-free, on-resin Alloc using readily available iodine/water environmentally sensible PolarClean (PC)/ethyl acetate (EtOAc) carried out one-pot manner with racemization-free couplings employing both 9-fluorenylmethoxycarbonyl (Fmoc) and amino acids (AAs). SPPS been demonstrated by performing consecutive removals–peptide couplings, whereas compatibility long peptides proven carrying an removal–coupling 39 AA resin. Upscaling 10 g was combined TFA-free resin cleavage, opening up opportunities for Alloc-AAs as synthons sustainable manufacturing.

Язык: Английский

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Glucose-dependent insulinotropic peptide and beyond: co-agonist innovations in the treatment of metabolic diseases

European Journal of Pharmacology, Год журнала: 2025, Номер 999, С. 177681 - 177681

Опубликована: Апрель 28, 2025

Язык: Английский

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Design and Biosynthesis of Ornithine 8-Containing Semaglutide Variants with a Click Chemistry-Modifiable Position 26

ACS Synthetic Biology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 30, 2025

Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, constitutes an effective and widely used treatment for type 2 diabetes obesity. However, challenges such as insufficient oral bioavailability, gastrointestinal side effects, high costs persist. Overcoming these limitations is essential improving patient compliance semaglutide's safety profile. While advanced technologies delivery systems offer partial solutions, optimizing the peptide structure crucial addressing issues. Establishing rapid method to generate large library of semaglutide mutants will enable high-throughput activity screening. In this study, we introduce novel "Fits-In-All" approach that combines ribosomally synthesized post-translationally modified (RiPP) technology with amber stop codon incorporation variants. To counter dipeptidyl peptidase-4-mediated cleavage, our strategically incorporates noncanonical amino acid ornithine at position 8 utilizing microbial modification enzyme OspR in vivo. Furthermore, functional groups are introduced by orthogonal tRNA/aminoacyl-tRNA synthetase pair recognizing 26, which enabled click chemistry-based linkage diverse groups. This allows generation broad array analogues can be screened optimal properties. conclusion, innovative opens new avenues design synthesis optimized peptide-based GLP-1 agonists.

Язык: Английский

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Therapeutic Peptides: Recent Advances in Discovery, Synthesis, and Clinical Translation

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(11), С. 5131 - 5131

Опубликована: Май 27, 2025

In recent decades, peptide-based therapeutics have undergone transformative advancements driven by breakthroughs in production, modification, and analytical technologies. Innovations chemical biological synthesis, coupled with novel design delivery strategies, systematically addressed historical limitations (e.g., poor stability bioavailability). These facilitated the characterization clinical translation of diverse natural engineered peptides across therapeutic domains, including metabolic disorders, oncology, infectious diseases. This review synthesizes critical developments peptide drug discovery, production technologies, applications, while highlighting emerging challenges opportunities. We further evaluate potential addressing unmet medical needs propose strategic directions to accelerate their integration into precision medicine paradigms.

Язык: Английский

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Design, synthesis, and biological evaluation of long-acting glucagon-like peptide-1 (GLP-1) conjugates modified with dual fatty acids and a proline-alanine-serine (PAS) polypeptide

Bioorganic & Medicinal Chemistry, Год журнала: 2025, Номер unknown, С. 118266 - 118266

Опубликована: Июнь 1, 2025

Язык: Английский

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