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Endocrine Disorders, Contraception, and Hormone Therapy during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
No studies of albiglutide use during human pregnancy are published. The manufacturer states that the drug should not be used in pregnancy because of the potential for harm to the embryofetus, citing studies in mice. Fetal and neonatal loss were increased, but not the frequency of congenital anomalies, in offspring of mice given up to 39 times the usual human dose during gestation. Notably, the manufacture’s warnings include discontinuation of albiglutide at least 30 days prior to conception because of the long washout period for the drug.
Pharmacotherapy
Published in G. Michael Steelman, Eric C. Westman, Obesity, 2016
GLP-1 receptor agonists (other than liraglutide [see above]), including exenatide and albiglutide, enhance insulin secretion, suppress glucagon, and slow gastric emptying. Clinical trials in patients with type 2 diabetes have demonstrated weight loss in the range of 1 to 3 kg over 26 to 52 weeks (108,109). Exenatide (Byetta®) is currently available in the United States, as is albiglutide (Tanzeum™). These agents are intended as add-on drugs for use in diabetics with poor glucose control and are not intended for monotherapy either for diabetes control or for weight loss.
Diabetes in Older Adults and Its Management
Published in K. Rao Poduri, Geriatric Rehabilitation, 2017
Susanne U. Miedlich, Steven D. Wittlin
The secretion of glucagon-like peptides (GLPs) from the gut was first described in 1968 and was attributed to L-cells, endocrine cells, similar to the ones found in pancreatic islets, with a predominant localization in the distal ileum (reviewed in Reference 78). Upon secretion, stimulated by nutrient ingestion, GLPs activate their respective GLP1- or GLP-2 receptors, class B G protein-coupled receptors (GPCR), which then activate G proteins with subsequent signaling through cAMP and protein kinase A (reviewed in Reference 78). Activation of GLP1-receptors stimulates pancreatic insulin secretion and synthesis, reduces glucagon secretion, and also reduces appetite and delays gastric emptying, exocrine pancreatic, and gastric acid secretion (reviewed in Reference 78). Appetite-reducing actions promote weight loss and are presumably mediated via direct activation of hypothalamic GLP-1 receptors rather than activation of peripheral vagal neurons (79,80). All of these actions mediate powerful glucose-lowering actions while promoting weight loss, drawing considerable attention to the development of GLP-1 receptor agonists (GLP-1RA) for therapy of both diabetes and/or obesity. Endogenous GLP-1 is rapidly cleaved (within 2 minutes) by dipeptidyl peptidase 4 (DPP4) to inactive metabolites, thus greatly limiting its usefulness as a drug (reviewed in Reference 78). Research efforts have thus focused on developing agonists that are resistant to DPP4 cleavage. The first available GLP-1RA was resistant to DPP4 cleavage due to a mutation of the cleavage site, exendin 4, was isolated from the venom of a lizard (Heloderma suspectum or gila monster). The synthesized amide version of exendin 4, exenatide, was approved for diabetes therapy in 2005 (reviewed in Reference 78). Since then, four more long-acting GLP-1RA have been approved for diabetes therapy (liraglutide, albiglutide, dulaglutide, and lixisenatide; (81)). In addition, a higher-dose preparation of liraglutide has now also been approved for therapy of obesity without diabetes (12/2014, per prescribing information). So far, the prospective studies with GLP-1RA show HbA1C reductions of up to 1.5% as well as an average weight loss of 3 kg (reviewed in Reference 81). Associated lower blood pressures, improved lipid profiles (reviewed in Reference 82), and also improved left ventricular function (83,84) suggest that GLP-1RA may confer an early benefit regarding cardiovascular outcomes. A meta-analysis of available placebo-controlled trials of GLP-1RA suggested a 25%–30% cardiovascular risk reduction in patients treated with a GLP1-RA (85). More important, a large prospective trial just confirmed significantly fewer cardiovascular events in high-risk diabetic patients when treated with liraglutide over placebo after about 4 years (86).
The complex interplay between diabetes mellitus and atrial fibrillation
Published in Expert Review of Cardiovascular Therapy, 2022
Mehmet Yildiz, Carl J. Lavie, Daniel P. Morin, Ahmet Afsin Oktay
The impact of glucagon-like peptide-1 (GLP-1) receptor agonists on the risk of AF remains unknown. However, these agents should theoretically reduce the risk of AF by inducing significant weight loss. Clinical trials have indicated that GLP-1 receptor agonists can slightly increase baseline heart rate [102]. Some earlier reports raised concern for increased risk of AF with the use of albiglutide (8.6 vs. 3.4 events per 1000 patient-years). Per the manufacturer’s decision, this GLP-1 receptor agonist is no longer available [103]. However, a more extensive follow-up meta-analysis of thirty-one RCTs of patients with T2DM treated with GLP-1 receptor agonists or placebo or any other anti-DM medications did not report any association between GLP-1 receptor agonist use and new-onset AF [104].
Evidence-based therapeutics for hyperglycemia in hospitalized noncritically ill patients
Published in Current Medical Research and Opinion, 2022
Abraham Edgar Gracia-Ramos, Juana Carretero-Gómez, Carlos E. Mendez, Francisco Javier Carrasco-Sánchez
There are presently seven GLP-1RAs available for use in T2D: exenatide, lixisenatide, liraglutide, exenatide of long-acting release, dulaglutide, albiglutide, and semaglutide. GLP-1RAs exert several metabolic effects that make them attractive drugs for the management of hyperglycemia in the hospital. These include glucose-dependent insulin secretion, inhibition of glucagon secretion (thereby preventing hypoglycemia, which is most likely to occur when used in combination with insulin therapy or SUs), suppression of hepatic glucose production, enhanced tissue sensitivity to insulin, and beneficial effects on cardiovascular risk factors50. The principal side effects, that may limit GLP-1RAs prescription in the hospitalized patients, are nausea and vomiting. Three of them, albiglutide, dulaglutide, and semaglutide, are administered by once-weekly injections, and perhaps this weekly administration schedule with fewer gastrointestinal effects would be beneficial to start during hospitalization or to continue if the patient previously used it. Furthermore, long-acting GLP-1RAs have a greater effect on fasting glucose levels, and, conversely, short-acting agents have a greater effect on postprandial glucose. These differences may lead the physician to choose the GLP-1RAs according to the hyperglycemic profile51,52.
Tackling type 2 diabetes-associated cardiovascular and renal comorbidities: a key challenge for drug development
Published in Expert Opinion on Investigational Drugs, 2021
Ernest A. Adeghate, Huba Kalász, Saeeda Al Jaberi, Jennifer Adeghate, Kornelia Tekes
REWIND and PIONEER 6 trials show that GLP-1RAs have some benefits in reducing major adverse cardiac events [54]. This group of antidiabetic drugs reduces the rate of hospitalization for heart failure (HF) and a modest benefit on MACE. GLP-1RA also reduces macroalbuminuria without influencing the degree of CKD [54]. Reports from the HARMONY trial showed that albiglutide, when given subcutaneously at a maximum dose of 50 mg/week reduced the risk of non-fatal MI compared to placebo [55]. Unfortunately, the number (24% of 9,463) of subjects who dropped out of the trial was high. In contrast, the EXSCEL study, which examined more than 10, 700 patients with a history of cardiovascular events showed that exenatide given once a week did not significantly reduce the risk of MACE when compared to placebo [56]. However, extracts from many large RCTs such as ELIXA showed that GLP-1RA improves cardiovascular outcomes in T2DM patients more effectively than DPP4i [53]. Analysis of data from the LEADER (Liraglutide Effect and Action in Diabetes Evaluation of Cardiovascular Outcome Results) and SUSTAIN 6 (Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes) trials showed that GLP-1RA reduced cardiorenal morbidities and mortality when compared to placebo [57,58] (Table 1).