A Review on Semaglutide: An Oral Glucagon-Like Peptide 1 Receptor Agonist in Management of Type 2 Diabetes Mellitus

Kalra, Sanjay; Sahay, Rakesh

doi:10.1007/s13300-020-00894-y

Cited by 33 publications

(40 citation statements)

References 43 publications

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“…Semaglutide is available in oral formulations due to the presence of sodium N‐(8‐[2‐hydroxybenzoyl] amino) caprylate, which inhibits its degradation 62 . Semaglutide reduces the risk of diabetic kidney disease but increases the risk of retinopathy 63 .…”

Section: Resultsmentioning

confidence: 99%

One hundred years since insulin discovery: An update on current and future perspectives for pharmacotherapy of diabetes mellitus

Seetharaman

Pawar

Advani

2021

Brit J Clinical Pharma

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Diabetes mellitus was considered a fatal malady until the discovery, extraction and commercial availability of insulins. Numerous other classes of drugs ranging from sulfonylureas to sodium‐glucose co‐transporter‐2 inhibitors were then marketed. However, with the prevalence of diabetes mellitus increasing every year, many more drugs and therapies are under investigation. This review article aimed to summarize the significant developments in the pharmacotherapy of diabetes mellitus and outline the progress made by the recent advances, 100 years since insulins were first extracted successfully. Insulin analogues and insulin delivery pumps have further improved glycaemic control in diabetes mellitus. Cardiovascular and renal outcome trials have changed the landscape of diabetology, with some of these drugs also efficacious in nondiabetics. Newer drug delivery systems are being evaluated to improve the efficacy and reduce the dosing frequency and adverse effects of antidiabetics. Some newer drugs with novel mechanisms of action targeting type 1 and type 2 diabetes have also shown promise in recent clinical trials. These drugs include dual glucose‐dependent insulinotropic polypeptide and glucagon‐like peptide 1‐agonists, glucokinase activators, anti‐CD3 monoclonal antibodies and glimins. Their efficacy needs to be evaluated in larger studies.

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Section: Resultsmentioning

confidence: 99%

One hundred years since insulin discovery: An update on current and future perspectives for pharmacotherapy of diabetes mellitus

Seetharaman

Pawar

Advani

2021

Brit J Clinical Pharma

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“…Applicability of the GLP-1 receptor agonist as a pill will allow for a simple initiation, maintenance and/or intensification of therapy, easing the fear of patients for injection therapy. Therefore, better adherence and less therapeutic inertia is expected with the use of oral semaglutide [35,37]. Based on the authors' clinical practice experiences, we have observed that individuals generally do not fully understand the difference between non-insulin and insulin injections.…”

Section: Discussionmentioning

confidence: 99%

Effect of Oral Semaglutide on Cardiovascular Parameters and Their Mechanisms in Patients with Type 2 Diabetes: Rationale and Design of the Semaglutide Anti-Atherosclerotic Mechanisms of Action Study (SAMAS)

et al. 2022

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Introduction: Type 2 diabetes (T2D) management has reached a point where not only optimal glycaemic control is necessary, but also additional interventions with proven cardiovascular risk reduction benefit. Subcutaneous semaglutide has been shown to provide cardiovascular protection, but its use may be limited by its injection formulation. To overcome this limitation, an oral semaglutide tablet has been developed, which could potentially be of the same value as its injection counterpart, but in a much wider group of patients with T2D, thereby allowing for broader cardiovascular risk reduction in this vulnerable patient population. Methods: A total of 100 consecutive patients with T2D and a disease duration of up to 10 years, without manifest cardiovascular disease, who are treated with metformin (± sulphonylurea) and optimal cardioprotective therapy, will be recruited in a single-blinded, randomized trial named ''Semaglutide Antiatherosclerotic Mechanisms of Action Study (SAMAS).'' After 1:1 randomization, patients will receive either oral semaglutide 14 mg daily or placebo for 1 year. The primary outcome comprises changes in atherosclerosis-related structural and functional characteristics of the arterial wall, namely: reduction of the carotid intima-media thickness, improvement of endothelial function and decrease in arterial stiffness. Secondary outcomes are changes in atherogenic small dense low-density lipoproteins, glucose control (HbA1c) and inflammatory markers (hsCRP). Possible correlations between primary endpoints and changes in

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“…Semaglutide is a GLP-1 RA that can be used subcutaneously once a week as a treatment for T2D [ 30 , 31 ]. This injectable molecule is a potent and long-acting GLP-1 analog with 94% homology with human native GLP-1 [ 32 ]. Three key structural differences provide the extended pharmacokinetics of this drug, namely, the substitution of Ala with Aib at position 8 that increases enzymatic (DPP4) stability, attachment of a linker and C18 di-acid chain at position 26 that provides strong binding to albumin and substitution of Lys with Arg at position 34 that prevents C18 fatty acid-binding at the wrong site [ 32 ].…”

Section: Development Of Oral Semaglutide: a Glp-1 Ra Peptidementioning

confidence: 99%

“…This injectable molecule is a potent and long-acting GLP-1 analog with 94% homology with human native GLP-1 [ 32 ]. Three key structural differences provide the extended pharmacokinetics of this drug, namely, the substitution of Ala with Aib at position 8 that increases enzymatic (DPP4) stability, attachment of a linker and C18 di-acid chain at position 26 that provides strong binding to albumin and substitution of Lys with Arg at position 34 that prevents C18 fatty acid-binding at the wrong site [ 32 ]. The phase 3 clinical trial program (SUSTAIN) compared subcutaneous semaglutide to placebo or other active standard-of-care medications in patients with T2D [ 30 , 31 ].…”

Section: Development Of Oral Semaglutide: a Glp-1 Ra Peptidementioning

confidence: 99%

Advances in GLP-1 treatment: focus on oral semaglutide

Eliaschewitz

Canani

2021

Diabetol Metab Syndr

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Background There is currently a large arsenal of antidiabetic drugs available to treat type 2 diabetes (T2D). However, this is a serious chronic disease that affects millions of adults worldwide and is responsible for severe complications, comorbidities, and low quality of life when uncontrolled due mainly to delays in initiating treatment or inadequate therapy. This review article aims to clarify the therapeutic role of the oral formulation of the glucagon-like peptide 1 receptor agonist (GLP-1 RA) semaglutide in treating typical T2D patients. The discussion focused on metabolic, glycemic, and weight alteration effects and the safety of the therapy with this drug. Main text Therapy with glucagon-like peptide 1 receptor agonist (GLP-1 RA) promotes strategic changes in the pathophysiological pathway of T2D and improves the secretion of glucagon and insulin, which results in a reduction in blood glucose levels and the promotion of weight loss. Until recently, the only route for semaglutide administration was parenteral. However, an oral formulation of GLP-1 RA was recently developed and approved by the Brazilian Health Regulatory Agency (ANVISA) and the Food and Drug Administration (FDA) based on the Peptide Innovation for Early Diabetes Treatment (PIONEER) program results. A sequence of 10 clinical studies compared oral semaglutide with placebo or active standard-of-care medications (empagliflozin 25 mg, sitagliptin 100 mg, or liraglutide 1.8 mg) in different T2D populations. Conclusions Oral semaglutide effectively reduces glycated hemoglobin (HbA1c) levels and body weight in a broad spectrum of patients with T2D and shows cardiovascular safety. Oral semaglutide broadens therapy options and facilitates the adoption of earlier GLP-1 RA treatment once T2D patients present low rates of treatment discontinuation. The main adverse events reported were related to the gastrointestinal tract, common to GLP-1 RA class drugs.

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A Review on Semaglutide: An Oral Glucagon-Like Peptide 1 Receptor Agonist in Management of Type 2 Diabetes Mellitus

Cited by 33 publications

References 43 publications

One hundred years since insulin discovery: An update on current and future perspectives for pharmacotherapy of diabetes mellitus

One hundred years since insulin discovery: An update on current and future perspectives for pharmacotherapy of diabetes mellitus

Effect of Oral Semaglutide on Cardiovascular Parameters and Their Mechanisms in Patients with Type 2 Diabetes: Rationale and Design of the Semaglutide Anti-Atherosclerotic Mechanisms of Action Study (SAMAS)

Advances in GLP-1 treatment: focus on oral semaglutide

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