A review of GLP‐1 receptor agonists in type 2 diabetes: A focus on the mechanism of action of once‐weekly agents

Cornell, Susan

doi:10.1111/jcpt.13230

Cited by 84 publications

(79 citation statements)

References 88 publications

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“…First, semaglutide is a long-acting GLP-1 RA. It can directly stimulate insulin secretion from pancreatic β-cells while suppressing glucagon release from pancreatic α-cells (Cornell, 2020). Specifically, the structure and pharmacokinetics of semaglutide are distinct from other GLP-1 RAs, as it shows 94% sequence homology with native GLP-1, sufficiently high GLP-1 receptor affinity, and exhibits an extended plasma halflife of approximately 1 week (Lau et al, 2015;Gallwitz and Giorgino, 2021).…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Subcutaneous and Oral Semaglutide Administration in Patients With Type 2 Diabetes: A Meta-Analysis

et al. 2021

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Background: This meta-analysis aimed to combine the data available from clinical trials to assess the effects of subcutaneous and oral semaglutide administration on glycemic control, weight management, and safety outcomes in patients with type 2 diabetes (T2D).Methods: We systematically searched for phase 3 randomized controlled trials (RCTs) that compared semaglutide with placebo or other anti-diabetic drugs in T2D patients. The primary outcome was the change from baseline in glycated hemoglobin (HbA1c) levels. Secondary efficacy endpoints included the change from baseline in body weight, achievement of HbA1c targets, and clinically significant weight loss. Key safety outcomes were also assessed.Results: In this meta-analysis, 24 trials with a total of 22185 patients were included. Subcutaneous semaglutide administration reduced HbA1c levels (weighted mean difference [WMD]: −1.14% and −1.37%, for 0.5 mg and 1 mg, respectively) and body weight (WMD: −2.73 kg and −4.09 kg, for 0.5 mg and 1 mg, respectively) when compared with placebo; its efficacy was also superior to other anti-diabetic drugs in reducing HbA1c levels (WMD: −0.71% and −0.86%, for 0.5 mg and 1 mg, respectively) and body weight (WMD: −2.65 kg and −3.78 kg, for 0.5 mg and 1 mg, respectively). Oral semaglutide administration was superior to placebo in decreasing HbA1c levels (WMD: −0.96% and −1.02%, for 7 mg and 14 mg, respectively). Moreover, oral administration of 14 mg of semaglutide also showed a significant reduction in HbA1c levels (WMD: −0.36%) compared with other anti-diabetic drugs. Furthermore, oral semaglutide administration resulted in substantial weight loss compared with other anti-diabetic drugs (WMD: −1.53 kg and −1.73 kg, for 7 mg and 14 mg, respectively). Notably, subcutaneous and oral semaglutide administration also resulted in higher numbers of patients achieving the targets of HbA1c levels and weight loss than placebo and other anti-diabetic drugs. Overall, we noted no clear evidence of detrimental effects on safety endpoints due to semaglutide treatment, except for some gastrointestinal adverse events.Conclusion: Both subcutaneous and oral semaglutide administration could enable the achievement of sufficient glycemic control and weight management without increasing the risk of hypoglycemia, which were effective and safe for the treatment of T2D.

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Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Subcutaneous and Oral Semaglutide Administration in Patients With Type 2 Diabetes: A Meta-Analysis

et al. 2021

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“…Glucose Like-Peptide 1 (GLP-1) is an incretin glucoregulatory hormone secreted from the enteroendocrine L cells of the intestinal mucosa after meal ingestion, which stimulates decreases glucagon secretion and insulin release when plasma glucose levels are raised [11][12][13]. It was initially discovered as an insulinotropic hormone produced in and released from the gut after food ingestion.…”

Section: Glp-1ra Background and Mechanism Of Actionmentioning

confidence: 99%

“…GLP-1 hormone exerts its efficacy via the GLP-1 receptor (GLP-1R) that belongs to the G-protein-coupled receptors family [12]. GLP-1R is expressed in various body tissues, including the brain, heart, pancreas, blood vessels of several organs, such as the gastrointestinal tract, lungs, and the kidneys [11,12]. Notably, the GLP-1 insulinotropic properties are maintained in human subjects with T2DM showing response failure to sulphonylurea [13].…”

Section: Glp-1ra Background and Mechanism Of Actionmentioning

confidence: 99%

“…GLP-1RA are generally divided based on their duration of action; Short-active GLP-1 RAs (lixisenatide and exenatide) exert short-lived receptor activation and provide greater post-prandial glucose reduction through delaying gastric discharging and facilitate slower delivery of glucose to the duodenum; The longeracting (dulaglutide, liraglutide-OD and exenatide ER, and semaglutide-OW) agents offer continual receptor activation at their suggested doses and provide longer half-lives pharmacokinetics (>3 hours). Therefore, the GLP-1RAs significantly reduce fasting blood glucose via agitating insulin release and hindrance of glucagon secretion from the pancreas, which makes them ideal for once-weekly dosing [11]. Multiple pharmaceutical industries have developed GLP-1RAs, of which six agents gained approval to treat diabetes and/or obesity [15].…”

Section: Glp-1ra Background and Mechanism Of Actionmentioning

confidence: 99%

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GLP-1 Receptor Agonist Cardiovascular Protection among Type-2 Diabetes Patients: A Literature Review

AlGhamdi¹,

Alqahtani²,

Alhazmi³

et al. 2021

Pharmacophore

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T2DM (Type 2 Diabetes Mellitus) remains a main global health issue, particularly if cardiovascular complications started to evolve. Type 2 diabetes is the main cause of renal and cardiovascular adverse consequences. Adequate management of T2DM depends on glycemic control and prevent cardiovascular or renal complications. Hence, certain antidiabetic agents have provided cardiovascular protection, of which one of them is the glucose-like peptide 1 receptor agonists. The present literature review aims to assess the cardiovascular efficiency and safety of glucose-like peptide 1 receptor agonists in patients with T2DM. We used the PubMed database, searching for relevant articles to the title. We used the following Mesh words: heart failure, GLP-1 receptor agonist, type 2 diabetes mellitus, cardiovascular consequences. GLP-1 receptor agonists are effective antidiabetic agents in regards to the glycemic control and safety profile for cardiovascular disease. GLP-1 receptor agonists seem to have promising cardiovascular protection in cardiovascular and all-cause mortality, including fatal and non-fatal myocardial infarction, fatal and non-fatal stroke. However, the increased risk of heart failure hospitalization remains debatable, and further clinical trials are recommended to evaluate this concern. A common side effect is related to gastrointestinal upset, and overall, it is transient and generally does not require discontinuation of the treatment.

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“…In healthy individuals, the increase of blood glucose levels after food intake leads to secretion of the incretin hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Once the incretin hormones bind to their receptors, a series of reactions (such as the potentiation of glucose-induced synthesis and secretion of insulin) take place in order to maintain the sugar homeostasis [ 1 , 2 ]. However, GLP-1 and GIP are rapidly hydrolyzed by the action of the enzyme DPP-IV, a prolyl peptidase that exists in blood and is ubiquitously expressed on the apical surface of endothelial and epithelial cells.…”

Section: Introductionmentioning

confidence: 99%

Magnetic ligand fishing using immobilized DPP-IV for identification of antidiabetic ligands in lingonberry extract

et al. 2021

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In this work, a new magnetic ligand fishing probe for discovery of DPP-IV inhibitory ligands was developed and it was tested as a proof of concept on the fruit extract of Vaccinium vitis-idaea (lingonberry). The ligands were shown to have appreciable dipeptidyl peptidase IV (DPP-IV) inhibitory activity (IC50: 31.8 μg mL-1).) Inhibition of DPP-IV is a well-known therapeutic approach for management of type 2 diabetes (T2D). DPP-IV was successfully immobilized onto magnetic beads and was shown to retain its catalytic activity and selectivity over a model mixture. A total of four ligands were successfully fished out and identified as cyanidin-3-galactoside (2), cyanidin-3-arabinoside (3), proanthocynidin A (4), and 10-carboxyl-pyranopeonidin 3-O-(6″-O-p-coumaroyl)-glucoside (5) using HPLC/HRMS.

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A review of GLP‐1 receptor agonists in type 2 diabetes: A focus on the mechanism of action of once‐weekly agents

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 84 publications

References 88 publications

Efficacy and Safety of Subcutaneous and Oral Semaglutide Administration in Patients With Type 2 Diabetes: A Meta-Analysis

Efficacy and Safety of Subcutaneous and Oral Semaglutide Administration in Patients With Type 2 Diabetes: A Meta-Analysis

GLP-1 Receptor Agonist Cardiovascular Protection among Type-2 Diabetes Patients: A Literature Review

Magnetic ligand fishing using immobilized DPP-IV for identification of antidiabetic ligands in lingonberry extract

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