Semaglutide—the “new kid on the block” in the field of glucagon-like peptide-1 receptor agonists?

Guja, Cristian; Miulescu, Rucsandra Dănciulescu

doi:10.21037/atm.2017.10.09

Cited by 8 publications

(5 citation statements)

References 20 publications

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“…It is associated with strong metabolic control and a decrease in body weight, with a safety profile characteristic of a GLP-1RA. In clinical trials, semaglutide reduced HbA1c by 1.5–1.8%, which was significantly more than active comparators, and was associated with a 4.5–6.4 kg weight loss [71].…”

Section: Glp-1 Its Receptor Agonists and Derived Metabolitesmentioning

confidence: 99%

GLP-1RAs in type 2 diabetes: mechanisms that underlie cardiovascular effects and overview of cardiovascular outcome data

Sposito

Berwanger

Carvalho

et al. 2018

Cardiovasc Diabetol

110

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Patients with type 2 diabetes (T2DM) have a substantial risk of developing cardiovascular disease. The strong connection between the severity of hyperglycaemia, metabolic changes secondary to T2DM and vascular damage increases the risk of macrovascular complications. There is a challenging demand for the development of drugs that control hyperglycaemia and influence other metabolic risk factors to improve cardiovascular outcomes such as cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina and heart failure (major adverse cardiovascular events). In recent years, introduction of the new drug class of glucagon-like peptide-1 receptor agonists (GLP-1RAs) has changed the treatment landscape as GLP-1RAs have become well-established therapies in T2DM. The benefits of GLP-1RAs are derived from their pleiotropic effects, which include appetite control, glucose-dependent secretion of insulin and inhibition of glucagon secretion. Importantly, their beneficial effects extend to the cardiovascular system. Large clinical trials have evaluated the cardiovascular effects of GLP-1RAs in patients with T2DM and elevated risk of cardiovascular disease and the results are very promising. However, important aspects still require elucidation, such as the specific mechanisms involved in the cardioprotective effects of these drugs. Careful interpretation is necessary because of the heterogeneity across the trials concerning the definition of cardiovascular risk or cardiovascular disease, baseline characteristics, routine care and event rates. The aim of this review is to describe the main clinical aspects of the GLP-1RAs, compare them using data from both the mechanistic and randomized controlled trials and discuss potential reasons for improved cardiovascular outcomes observed in these trials. This review may help clinicians to decide which treatment is most appropriate in reducing cardiovascular risk in patients with T2DM.

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Section: Glp-1 Its Receptor Agonists and Derived Metabolitesmentioning

confidence: 99%

GLP-1RAs in type 2 diabetes: mechanisms that underlie cardiovascular effects and overview of cardiovascular outcome data

Sposito

Berwanger

Carvalho

et al. 2018

Cardiovasc Diabetol

110

View full text Add to dashboard Cite

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“…In the case of insulin detemir, linking an insulin analog to myristic acid facilitates prolonged action compared with postprandial treatments (Poon and King, 2010). Similarly, conjugation of the glucagon-like peptide-1 (GLP-1) receptor agonist analog, semaglutide, to a 18-carbon fatty acid chain, led to a half-life of ;168 hours in humans and supported a once weekly dosing interval for the peptide compared with nonfatty acid containing GLP-1 receptor agonist molecules, which have a daily dosing frequency due to their short half-lives (less than ;3-6 hours) (Guja and D anciulescu Miulescu, 2017).…”

Section: Molecule-centric Phsiochemical Factors Influencing Dispositimentioning

confidence: 99%

Mechanisms Influencing the Pharmacokinetics and Disposition of Monoclonal Antibodies and Peptides

Datta‐Mannan

2019

Drug Metab Dispos

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Monoclonal antibodies (mAbs) and peptides are an important class of therapeutic modalities that have brought improved health outcomes in areas with limited therapeutic optionality. Presently, there more than 90 mAb and peptide therapeutics on the United States market, with over 600 more in various clinical stages of development in a broad array of therapeutic areas, including diabetes, autoimmune disorders, oncology, neuroscience, and cardiovascular and infectious diseases. Notwithstanding this potential, there is high clinical rate of attrition, with approximately 10% reaching patients. A major contributor to the failure of the molecules is often times an incomplete or poor understanding of the pharmacokinetics (PK) and disposition profiles leading to limited or diminished efficacy. Increased and thorough characterization efforts directed at disseminating mechanisms influencing the PK and disposition of mAbs and peptides can aid in improving the design for their intended pharmacological activity, and thereby their clinical success. The PK and disposition factors for mAbs and peptides are broadly influenced by target-mediated drug disposition and nontarget-related clearance mechanisms related to the interplay between the relationship of the structure and physiochemical properties of mAbs and peptides with physiologic processes. This review focuses on nontarget-related factors influencing the disposition and PK of mAbs and peptides. Contemporary considerations around the increasing in silico approaches to identify nontarget-related molecule limitations and enhancing the druggability of mAbs and peptides, including parenteral and nonparenteral delivery strategies that are geared toward improving patient experience and compliance, are also discussed.

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“…Semaglutide is a GLP-1 receptor agonists administered by subcutaneous injection [ 52 ]. It acts as an adjunctive therapy in the treatment of patient with T2DM with a controlled diet and exercise to improve the glycemia control [ 52 , 53 , 54 , 55 ]. The approved therapeutic dose of semaglutide are 0.5 mg and 1 mg.…”

Section: Resultsmentioning

confidence: 99%

“…It must be administered as once weekly on the same day every week and either same or different time of the day [ 55 ]. Semaglutide is not recommended for patient with type 1 diabetes or diabetic ketoacidosis [ 52 , 53 ].…”

Section: Resultsmentioning

confidence: 99%

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Systematic Review of Efficacy and Safety of Newer Antidiabetic Drugs Approved from 2013 to 2017 in Controlling HbA1c in Diabetes Patients

et al. 2018

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Type 2 Diabetes Mellitus (T2DM) is the most common form of diabetes mellitus and accounts for about 95% of all diabetes cases. Many newer oral as well as parenteral antidiabetic drugs have been introduced in to the market in recent years to control hyperglycemic conditions in diabetes patients and many of these drugs produce potential side effects in diabetes patients. Hence, this systematic review was aimed to analyze and compare the efficacy and safety of oral antidiabetic agents in controlling HbA1c in T2DM patients, that were approved by the United States-Food and Drug Administration (US-FDA) from 2013 to 2017. All randomized controlled, double-blind trials published in English during the search period involving the newer antidiabetic agents were selected. In the outcome assessment comparison, semaglutide demonstrated the highest efficacy in lowering HbA1c, with a 1.6% reduction (p < 0.0001) when given at a dose of 1.0 mg. The safety profile of all the agents as compared to placebo or control were similar, with no or slight increase in the occurrence of adverse events (AEs) but no fatal reaction was reported. The most common AEs of all the antidiabetic agents were gastrointestinal in nature, with several cases of hypoglycemic events. However, among all these agents, semaglutide seems to be the most efficacious drug to improve glycemic control in terms of HbA1c. Alogliptin has the least overall frequency of AEs compared to other treatment groups.

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Semaglutide—the “new kid on the block” in the field of glucagon-like peptide-1 receptor agonists?

Abstract: Comment on: Sorli C, Harashima SI, Tsoukas GM, et al. Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes (SUSTAIN 1): a double-blind, randomised, placebo-controlled, parallel-group, multinational, multicentre phase 3a trial. Lancet

Cited by 8 publications

References 20 publications

GLP-1RAs in type 2 diabetes: mechanisms that underlie cardiovascular effects and overview of cardiovascular outcome data

GLP-1RAs in type 2 diabetes: mechanisms that underlie cardiovascular effects and overview of cardiovascular outcome data

Mechanisms Influencing the Pharmacokinetics and Disposition of Monoclonal Antibodies and Peptides

Systematic Review of Efficacy and Safety of Newer Antidiabetic Drugs Approved from 2013 to 2017 in Controlling HbA1c in Diabetes Patients

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