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Diabetes Mellitus, Obesity, Lipoprotein Disorders and other Metabolic Diseases
Published in John S. Axford, Chris A. O'Callaghan, Medicine for Finals and Beyond, 2023
GLP-1 is an incretin hormone which augments insulin release and inhibits glucagon release from the pancreas. GLP-1 has a short half-life because it is inactivated by proteases including dipeptidyl protease IV. A variety of drugs with GLP-1 receptor agonist activity are licensed for type 2 DM including exenatide, liraglutide, lixisenatide and semaglutide.
The Management of Patients with Heart Failure and Diabetes
Published in Andreas P. Kalogeropoulos, Hal A. Skopicki, Javed Butler, Heart Failure, 2023
Studies have shown that the glucagon-like peptide-1 (GLP-1) agonist, liraglutide, is associated with lower rates of all-cause mortality, cardiovascular mortality, non-fatal myocardial infarction, and non-fatal CVA. Liraglutide, however, failed to reduce HF hospitalizations.31 GLP-1 agonists stimulate the distal ileum to release GLP-1, which raises insulin levels while lowering glucagon, and promotes satiety by delaying gastric emptying.67 Contraindications to GLP-1 agonist use include hypersensitivity, end-stage renal disease, family or personal history of medullary thyroid cancer, or multiple endocrine neoplasia syndrome type 2 (MEN-2). Adverse events include resting tachycardia, increase in pancreatitis, mood disorders, and renal injury.68
Endocrine Disorders, Contraception, and Hormone Therapy during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
Semaglutide is a relatively new GLP-1 inhibitor that has not been studied on human pregnancy. The manufacturer reports that in animal studies birth defects and pregnancy losses occurred in pregnancies exposed to the drug during organogenesis. No pregnancy risk categories are assigned to this agent; however, it is noted in the manufacturer’s package literature that the drug should be discontinued two months before conception. No studies of excretion into breast milk are published but the manufacturer states that it is transferred into animal breast milk.
Comparing the bioequivalence and safety of liraglutide in healthy Chinese subjects: an open, single-dose, randomized, repeated, two-sequence, two-cycle phase I clinical trial
Published in Expert Review of Clinical Pharmacology, 2023
Zhongnan Xu, Zhengzhi Liu, Yanli Wang, Jinling Xue, Tianying Chang, Yingzi Cui, Yang Cheng, Guangwen Liu, Wanhua Wang, Yannan Zhou, Shuang Yu, Qing Ren, Wei Yang, Xinyao Qu, Jiahui Chen, Xuesong Chen, Qiaohuan Deng, Haimiao Yang, Xiuge Wang
GLP-1 has become a new treatment for type 2 diabetes mellitus [2]. GLP-1 is an endogenous incretin hormone [10]. GLP-1 has been shown to stimulate insulin, inhibit glucagon secretion, increase hepatic glucose production, inhibit gastric emptying, promote satiety and reduce food intake [11–15]. Liraglutide, an antidiabetic medication, is a GLP-1 receptor agonist (GLP-1RA). It can improve insulin secretion and inhibit the secretion of glucagon, thereby lowering blood sugar [16]. A study has shown that liraglutide improves postprandial blood glucose compared to placebo or rosiglitazone [17]. In a trial comparing liraglutide with placebo and glimepiride in combination with metformin, liraglutide was significantly better at controlling blood sugar than placebo, comparable to glimepiride’s control [18]. Liraglutide was approved for treating type 2 diabetes mellitus in Europe and the United States in 2009 and 2010, respectively [19]. Liraglutide has significant advantages over other antidiabetic drugs in delaying β cell failure and reducing cardiovascular complications in diabetes [20–22]. The patent of liraglutide (Victoza®) invented by Novo Nordisk A/S will expire in 2023. And its generic formulations are being developed and the promotion and application are waiting for the expiration.
The potential role of GLP-1 receptor agonist targeting in fertility-sparing treatment in obese patients with endometrial malignant pathology: a call for research
Published in Expert Review of Anticancer Therapy, 2023
Caroline J. Violette, Ravi Agarwal, Rachel S. Mandelbaum, José L. González, Kurt M. Hong, Lynda D. Roman, Maximilan Klar, Jason D. Wright, Richard J. Paulson, Andreas Obermair, Koji Matsuo
Semaglutide allows for once weekly subcutaneous injection dosing due to its long half-life of 7 days, which may also improve patient satisfaction and compliance for many patients compared to earlier generation of GLP-1 RAs requiring daily subcutaneous injection dosing [74,75]. Additionally, the semaglutide is metabolized via proteolytic cleavage and beta oxidation, which is not confined to a single organ [76]. Importantly, animal studies have demonstrated reproductive toxicity with all GLP-1 RAs, therefore while human data is lacking, their use during pregnancy and/or breastfeeding is contraindicated at this time [77]. Pre-conception counseling is necessary once the patient achieves a complete response and prepares for future pregnancy to find a medication alternative. Given animal studies demonstrate teratogenicity without adequate studies in human pregnancy, the recommendation would be to discontinue the use of GLP-1 RAs prior to attempting pregnancy [77].
The correlations between steady-state concentration, duration of action and molecular weight of GLP-1RAs and their efficacy and gastrointestinal side effects in patients with type 2 diabetes mellitus: a systematic review and meta-analysis
Published in Expert Opinion on Pharmacotherapy, 2023
Ruoyang Jiao, Chu Lin, Shuzhen Bai, Xiaoling Cai, Suiyuan Hu, Fang Lv, Wenjia Yang, Xingyun Zhu, Linong Ji
As for the relationship between the concentration of GLP-1RA and hypoglycemic effect, a dose-response relationship was proved previously. It was found that the plasma exenatide concentration increased in a dose-dependent manner, and the plasma exenatide concentration seemed to show a pharmacokinetic characteristic that was proportional to the dose [20]. Liraglutide showed significant dose-dependent responses on the level of HbA1c reductions from 0.6 mg, 1.2 mg to 1.8 mg [21]. A meta-analysis showed that the highest dose was associated with a greater decrease in mean HbA1c and increased the proportion of patients who reached the target HbA1c [22]. A dose-response relationship was also observed in the recombinant GLP-1 administered by continuous subcutaneous infusion. Hypoglycemic effect improved as the infusion dose of recombinant GLP-1 increased, reflecting on parameters of fasting blood glucose, postprandial peak serum glucose and incremental area under the curves, and 11-h serum glucose profiles [23]. Based on previous evidence, it was suggested that within a certain range, the higher the blood concentration of GLP-1RA, the better the hypoglycemic efficacy. Consistently, our study also confirmed an augmented hypoglycemic effect in high steady-state concentration stratum.