Glucokinase activators and imeglimin: new weaponry in the armamentarium against type 2 diabetes DOI Creative Commons
Åke Sjöholm

BMJ Open Diabetes Research & Care, Journal Year: 2024, Volume and Issue: 12(4), P. e004291 - e004291

Published: Aug. 1, 2024

The prevalence of type 2 diabetes (T2D) is increasing relentlessly all over the world, in parallel with a similar increase obesity, and striking ever younger patients. Only minority patients T2D attain glycemic targets, indicating clear need for novel antidiabetic drugs that not only control glycemia but also halt or slow progressive loss β-cells. Two entirely classes agents—glucokinase activators imeglimin—have recently been approved will be subject this review. Allosteric glucokinase, an enzyme stimulating insulin secretion β-cells suppressing hepatic glucose production, are oral low-molecular-weight drugs. One these, dorzagliatin, China use adult T2D, either as monotherapy add-on to metformin. It remains seen whether drug produce sustained effects many years side led discontinuation early candidates limit usefulness dorzagliatin. Imeglimin—which shares structural similarities metformin—targets mitochondrial dysfunction was Japan against T2D. In preclinical studies, has shown promising β-cell protective preservative may translate into disease-modifying effects. Hopefully, these two newcomers contribute filling great medical new treatment modalities, preferably potential. where they fit contemporary algorithms, which combinations effective should avoided. Time tell what extent agents add value current options terms effect, acceptable safety, utility combination therapy, impact on hard end-points such cardiovascular disease.

Language: Английский

Risk of major adverse cardiovascular events and all-cause mortality under treatment with GLP-1 RAs or the dual GIP/GLP-1 receptor agonist tirzepatide in overweight or obese adults without diabetes: a systematic review and meta-analysis DOI Creative Commons
Maria‐Ioanna Stefanou, Lina Palaiodimou, Aikaterini Theodorou

et al.

Therapeutic Advances in Neurological Disorders, Journal Year: 2024, Volume and Issue: 17

Published: Jan. 1, 2024

Background: Among the currently approved antiobesity medications, glucagon-like-peptide-1 receptor-agonists (GLP-1 RAs) liraglutide and semaglutide, dual glucose-dependent-insulinotropic-polypeptide (GIP)/GLP-1 RA tirzepatide have been suggested to reduce cardiovascular-risk in overweight or obesity without diabetes. Objectives: The objective of this study was evaluate cardio- neuroprotective potential these novel agents nondiabetic overweight/obese adult population. Data sources methods: A systematic review meta-analysis randomized-controlled clinical trials (RCTs) performed estimate risk major adverse cardiovascular events (MACE), all-cause mortality obese adults diabetes treated with GLP-1 GIP/GLP-1 RAs (vs placebo). Secondary outcomes included myocardial infarction (MI) stroke. Results: Sixteen RCTs (13 3 on tirzepatide, respectively) comprising 28,168 participants were included. reduced MACE (odds ratio (OR): 0.79; 95% confidence interval (CI): 0.71–0.89; p < 0.01; I 2 = 0) (OR: 0.80; CI: 0.70–0.92; 0), while there a trend toward lower cardiovascular-mortality 0.84; 0.71–1.01; 0.06; 0%) compared placebo. Additionally, odds MI 0.72; 0.61–0.86; nonfatal-MI 0.61–0.85; 0%); no associations between treatment fatal-MI, stroke, nonfatal, fatal stroke uncovered. Conclusion: attenuate MI. Since data are still limited, future warranted agents. Trial registration: PROSPERO CRD42024515966.

Language: Английский

Citations

6
Glucagon-Like Peptide-1 Based Therapies: A New Horizon in Obesity Management DOI Creative Commons
Jang Won Son, Soo Lim

Endocrinology and Metabolism, Journal Year: 2024, Volume and Issue: 39(2), P. 206 - 221

Published: April 16, 2024

Obesity is a significant risk factor for health issues like type 2 diabetes and cardiovascular disease. It often proves resistant to traditional lifestyle interventions, prompting need more precise therapeutic strategies. This has led focus on signaling pathways neuroendocrine mechanisms develop targeted obesity treatments. Recent developments in management have been revolutionized by introducing novel glucagon-like peptide-1 (GLP-1) based drugs, such as semaglutide tirzepatide. These drugs are part of an emerging class nutrient-stimulated hormone-based therapeutics, acting incretin mimetics target G-protein–coupled receptors GLP-1, glucose-dependent insulinotropic polypeptide (GIP), glucagon. vital regulating body fat energy balance. The development multiagonists, including GLP-1–glucagon GIP–GLP-1–glucagon receptor agonists, especially with the potential glucagon activation, marks advancement field. review covers clinical efficacy various GLP-1-based exploring challenges future directions management.

Language: Английский

Citations

5
GIP attenuates neuronal oxidative stress by regulating glucose uptake in spinal cord injury of rat DOI Creative Commons
Beibei Guo,

Mengwei Qi,

Xiaoqian Luo

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(6)

Published: June 1, 2024

Glucose-dependent insulinotropic polypeptide (GIP) is a ligand of glucose-dependent receptor (GIPR) that plays an important role in the digestive system. In recent years, GIP has been regarded as hormone-like peptide to regulate local metabolic environment. this study, we investigated antioxidant on neuron and explored possible mechanism.

Language: Английский

Citations

5
Incretins and cardiovascular disease: to the heart of type 2 diabetes? DOI Creative Commons
Anna Solini, Domenico Tricò, Stefano Del Prato

et al.

Diabetologia, Journal Year: 2023, Volume and Issue: 66(10), P. 1820 - 1831

Published: Aug. 5, 2023

Major cardiovascular outcome trials and real-life observations have proven that glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs), regardless of structural GLP-1 homology, exert clinically relevant protection. GLP-1RAs provide cardioprotective benefits through glycaemic non-glycaemic effects, including improved insulin secretion action, body-weight loss, blood-pressure lowering lipid profile, as well via direct effects on the heart vasculature. These actions are likely combined with anti-inflammatory antioxidant properties translate into robust consistent reductions in atherothrombotic events, particularly people type 2 diabetes established atherosclerotic CVD. may also an impact obesity chronic kidney disease, conditions for which risk-reducing options limited. The available evidence has prompted professional medical societies to recommend mitigation risk diabetes. This review summarises clinical protection use main mechanisms underlying this effect. Moreover, it looks how availability upcoming dual triple incretin might expand possibility

Language: Английский

Citations

13
Seeking satiety: From signals to solutions DOI

Matthias H. Tschöp,

Jeffrey M. Friedman

Science Translational Medicine, Journal Year: 2023, Volume and Issue: 15(723)

Published: Nov. 22, 2023

Remedies for the treatment of obesity date to Hippocrates, when patients with were directed “reduce food and avoid drinking fullness” begin “running during night.” Similar recommendations have been repeated ever since, despite fact that they are largely ineffective. Recently, highly effective therapeutics developed may soon enable physicians manage body weight in a manner similar way blood pressure is controlled hypertension. These medicines grown out revolution our understanding molecular neural control appetite weight, reviewed here.

Language: Английский

Citations

12
Incretin-based drugs decrease the incidence of prostate cancer in type 2 diabetics: A pooling-up analysis DOI Creative Commons
Yuxiang Lin,

Guangyong Xu,

Liangyu Li

et al.

Medicine, Journal Year: 2024, Volume and Issue: 103(20), P. e38018 - e38018

Published: May 17, 2024

Incretin-based drugs, a class of Antidiabetic medications (ADMs) used in the treatment type 2 diabetes, may affect incidence prostate cancer (PCa). But real-world evidence for this possible effect is lacking. Therefore, aim study to assess incretin-based drugs on PCa, including glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors. We searched PubMed, Embase, Cochrane Library databases eligible studies through September 2023. Two independent reviewers performed screening data extraction. Handbook Systematic Reviews Newcastle-Ottawa Scale (NOS) quality included randomized controlled trials (RCTs) cohort studies. did meta-analysis available trial calculate overall risk ratios (RRs) PCa. A total 1238 articles were identified our search. After eligibility, 7 high-quality met criteria meta-analysis, RCTs 5 studies, with 1165,738 patients. Compared control group, we found that reduced relative PCa by 35% (95% confidence interval (CI), 0.17-0.49; P = .0006). In subgroup analysis, RR values GLP-1 DPP-4 inhibitors 62% CI, 0.45-0.85; .003) 72% 0.46-1.12; .14), respectively. are associated lower have preventive patients diabetes.

Language: Английский

Citations

4
Long‐term safety and efficacy of glucagon‐like peptide‐1 receptor agonists in individuals with obesity and without type 2 diabetes: A global retrospective cohort study DOI
Yu‐Nan Huang, Wen‐Ling Liao, Jing‐Yang Huang

et al.

Diabetes Obesity and Metabolism, Journal Year: 2024, Volume and Issue: 26(11), P. 5222 - 5232

Published: Aug. 22, 2024

We aimed to investigate the long-term impact of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on thyroid function, cardiovascular health, renal outcomes and adverse events in individuals with obesity without type 2 diabetes (T2D).

Language: Английский

Citations

4
Obesity-driven hunger: From pathophysiology to intervention DOI
Ahmad Khusairi Azemi, Yahkub Babatunde Mutalub, Monsurat Abdulwahab

et al.

Obesity Medicine, Journal Year: 2025, Volume and Issue: unknown, P. 100588 - 100588

Published: Feb. 1, 2025

Language: Английский

Citations

0
Medical management of obesity: unlocking the potential DOI Creative Commons
Angie S. Xiang, Priya Sumithran

Climacteric, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 5

Published: Feb. 7, 2025

After a long and challenging history, there have finally been major breakthroughs in the development of effective obesity medications. Agents that act at receptors one or more gut hormones are achieving unprecedented weight reductions improvements cardiovascular risk factors, comparable to some bariatric surgical procedures. Importantly, is evidence beneficial effects on growing range conditions, including type 2 diabetes, fatty liver, chronic kidney disease, obstructive sleep apnea disease. Barriers access need be overcome allow standard care for match other diseases.

Language: Английский

Citations

0
Advances in Oral Biomacromolecule Therapies for Metabolic Diseases DOI Creative Commons
Qiuxia Jiao, Yuan Huang, Jinhan He

et al.

Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(2), P. 238 - 238

Published: Feb. 12, 2025

Metabolic diseases like obesity and diabetes are on the rise, therapies with biomacromolecules (such as proteins, peptides, antibodies, oligonucleotides) play a crucial role in their treatment. However, these drugs traditionally injected. For patients chronic (e.g., metabolic diseases), long-term injections accompanied by inconvenience low compliance. Oral administration is preferred, but delivery of challenging due to gastrointestinal barriers. In this article, we introduce available biomacromolecule for treatment diseases. The barriers oral drug strategies overcome also explored. We then discuss alleviating defects, including glucose metabolism, lipid energy such insulin, glucagon-like peptide-1 receptor agonists, proprotein convertase subtilisin/kexin type 9 inhibitors, fibroblast growth factor 21 analogues, peptide YY analogues.

Language: Английский

Citations

0