Treatment strategies against diabetes: Success so far and challenges ahead

European Journal of Pharmacology, Journal Year: 2019, Volume and Issue: 862, P. 172625 - 172625

Published: Aug. 23, 2019

Language: Английский

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Trends in Antidiabetic Drug Discovery: FDA Approved Drugs, New Drugs in Clinical Trials and Global Sales

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 12

Published: Jan. 19, 2022

Type 2 diabetes mellitus (T2DM) continues to be a substantial medical problem due its increasing global prevalence and because chronic hyperglycemic states are closely linked with obesity, liver disease several cardiovascular diseases. Since the early discovery of insulin, numerous antihyperglycemic drug therapies treat have been approved, also discontinued, by United States Food Drug Administration (FDA). To provide an up-to-date account current trends antidiabetic pharmaceuticals, this review offers comprehensive analysis main classes compounds their mechanisms: insulin types, biguanides, sulfonylureas, meglitinides (glinides), alpha-glucosidase inhibitors (AGIs), thiazolidinediones (TZD), incretin-dependent therapies, sodium-glucose cotransporter type (SGLT2) combinations thereof. The number therapeutic alternatives T2DM now there nearly 60 drugs approved FDA. Beyond 100 additional agents being evaluated in clinical trials. In addition standard treatments therapy metformin, new combinations, e.g., containing SGLT2 dipeptidyl peptidase-4 (DPP4) inhibitors, that gained use during last decade. Furthermore, interesting alternatives, such as lobeglitazone, efpeglenatide tirzepatide, ongoing Modern drugs, glucagon-like peptide-1 (GLP-1) receptor agonists, DPP4 popularity on pharmaceutical market, while less expensive over counter developing economies. large heterogeneity is creating push towards more personalized accessible treatments. We describe trials, which may help achieve near future.

Language: Английский

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A deep-learning framework for multi-level peptide–protein interaction prediction

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Sept. 15, 2021

Abstract Peptide-protein interactions are involved in various fundamental cellular functions and their identification is crucial for designing efficacious peptide therapeutics. Recently, a number of computational methods have been developed to predict peptide-protein interactions. However, most the existing prediction approaches heavily depend on high-resolution structure data. Here, we present deep learning framework multi-level interaction prediction, called CAMP, including binary corresponding binding residue identification. Comprehensive evaluation demonstrated that CAMP can successfully capture between peptides proteins identify residues along In addition, outperformed other state-of-the-art prediction. serve as useful tool important peptides, which thus facilitate drug discovery process.

Language: Английский

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GLP-1 and GIP receptor signaling in beta cells – A review of receptor interactions and co-stimulation

Peptides, Journal Year: 2022, Volume and Issue: 151, P. 170749 - 170749

Published: Jan. 19, 2022

Glucagon-like peptide 1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide (GIPR) are two class B1 G protein-coupled receptors, which stimulated by the gastrointestinal hormones GLP-1 GIP, respectively. In pancreatic beta cells, activation of both receptors lead to increased cyclic adenosine monophosphate (cAMP) insulin secretion. Marketed GLP-1R agonists such as dulaglutide, liraglutide, exenatide semaglutide constitute an expanding drug with beneficial effects for persons suffering from type 2 diabetes and/or obesity. recent years another class, GLP-1R-GIPR co-agonists, has emerged. Especially peptide-based, co-agonist tirzepatide is a promising candidate better treatment improving glycemic control weight reduction. The mechanism action include biased signaling well potent GIPR signaling. Since implications co-targeting these closely related concomitantly challenging study in vivo, pharmacodynamic mechanisms downstream pathways co-agonists general, not fully elucidated. this review, we present individual cell focus on shared interpret co-activation light co-activating therapeutic compounds.

Language: Английский

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Mechanisms and possible hepatoprotective effects of glucagon-like peptide-1 receptor agonists and other incretin receptor agonists in non-alcoholic fatty liver disease

˜The œLancet. Gastroenterology & hepatology, Journal Year: 2023, Volume and Issue: 8(2), P. 179 - 191

Published: Jan. 5, 2023

Language: Английский

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Obesity and MASLD: Is weight loss the (only) key to treat metabolic liver disease?

Metabolism, Journal Year: 2024, Volume and Issue: 157, P. 155937 - 155937

Published: May 21, 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD) closely associates with obesity and type 2 diabetes. Lifestyle intervention bariatric surgery aiming at substantial weight loss are cornerstones of MASLD treatment by improving histological outcomes reducing risks comorbidities. Originally developed as antihyperglycemic drugs, incretin (co-)agonists SGLT2 inhibitors also reduce steatosis cardiorenovascular events. Certain agonists effectively improve features MASLD, but not fibrosis. Of note, beneficial effects on may necessarily require loss. Despite moderate gain, one PPARγ agonist improved adipose tissue certain benefit fibrosis in post-hoc analyses. Likewise, the first THRβ-agonist was recently provisionally approved because significant improvements We here discuss liver-related metabolic induced different treatments their association Therefore, we compare results from clinical trials drugs acting via (incretin (co)agonists, inhibitors) those exerting no (pioglitazone; resmetirom). Furthermore, other development directly targeting hepatic lipid metabolism (lipogenesis inhibitors, FGF21 analogs) addressed. Although THRβ-agonism outcomes, concepts should consider all cardiometabolic risk factors for effective reduction morbidity mortality affected people.

Language: Английский

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Glucagon-like Peptide-1 Receptor Agonists Associated Gastrointestinal Adverse Events: A Cross-Sectional Analysis of the National Institutes of Health All of Us Cohort

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(2), P. 199 - 199

Published: Feb. 2, 2024

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are commonly used diabetes and obesity medications but have been associated with gastrointestinal (GI) adverse events. However, real-world evidence on comparative GI reaction profiles is limited. Objectives: This study aimed to evaluate events among GLP-1 RA users compare semaglutide, dulaglutide, liraglutide, exenatide safety regarding the profile. Methods: retrospective cross-sectional analysis utilized data 10,328 adults diabetes/obesity in National Institutes of Health All Us cohort. New were identified, examined. Logistic regression determined factors Results: The mean age population was 61.4 ± 12.6 years, 65.7% female, 51.3% White, they had a high comorbidity burden. Abdominal pain (57.6%) most common event, followed by constipation (30.4%), diarrhea (32.7%), nausea vomiting (23.4%), bleeding (15.9%), gastroparesis (5.1%), pancreatitis (3.4%). Dulaglutide liraglutide higher rates abdominal pain, constipation, diarrhea, than semaglutide exenatide. Liraglutide highest (4.0% 3.8%, respectively). Compared dulaglutide odds vomiting. They also semaglutide. No significant differences existed or risks between RAs. Conclusions: In this cohort, Differences agents, appearing safer other RAs, except for gastroparesis. These findings can inform selection considering risk factors. Further studies needed causal relationship concomitant medication use.

Language: Английский

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Association of glucagon-like peptide-1 receptor agonists with risk of cancers-evidence from a drug target Mendelian randomization and clinical trials

International Journal of Surgery, Journal Year: 2024, Volume and Issue: unknown

Published: May 3, 2024

Glucagon-like peptide-1 receptor (GLP1R) agonists have been approved by Food and Drug Administration for management of obesity. However, the causal relationship GLP1R (GLP1RA) with cancers still unclear.

Language: Английский

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A feeding-induced myokine modulates glucose homeostasis

Nature Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Language: Английский

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Functional dynamics of G protein-coupled receptors reveal new routes for drug discovery

Nature Reviews Drug Discovery, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Language: Английский

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