Advances in GLP-1 treatment: focus on oral semaglutide

Abstract

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.

Oral Delivery of Therapeutic Antibodies with a Transmucosal Polymeric Carrier

“…As shown in this work, FCS would self-assemble with various therapeutic proteins to form stable nanocomplexes, which are lyophilized in the presence of mannitol and then loaded into enteric capsules for oral feeding (Figure a). According to the pharmacokinetic behavior of IgG after oral administration, oral delivery of an antibody with the help of FCS was realized, reaching a bioavailability as high as 4.73% in mice, in marked contrast to that of reported oral peptide drugs such as Mycapssa and Rybelsus (bioavailability of 0.25–1%). , We found that oral delivery of checkpoint antibodies such as αPD1 or αCTLA4 could indeed effectively activate the immune system. Using a 5-fold dose of the intravenous (i.v.)…”

A new era in gut hormone-based pharmacotherapy for people with obesity

“…Semaglutide is the latest generation GLP-1RA analogue for chronic weight management in adults with obesity or overweight with at least one weight related comorbidity, as an adjunct to lifestyle intervention. Similar to liraglutide, semaglutide offers the unique advantage of glycaemic regulation by stimulating insulin secretion and decreases glucagon secretion which improves glycaemic control (65) . Semaglutide was initially approved for T2D therapy use of up to 1.0mg via subcutaneous injection (66) or up to 14mg once-daily oral administration in 2017 and 2019, respectively, by the EMA and FDA (67) .…”

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“…90% of these cases are represented by type 2 DM, although more than 50% of them did not have access to early diagnosis and adequate treatment. Furthermore, 374 million people have insulin resistance (IR) which increases their chance of developing type 2 DM [18,24]. Obesity is considered as a lifelong progressive disease with periods of remission and recurrences that plays a significant role in the evolution of DM and its clinical manifestations [54].…”