Future perspectives in diabesity treatment: Semaglutide, a glucagon‑like peptide 1 receptor agonist (Review)

Abstract

Given their endemic prevalence in the past decades, obesity and type 2 diabetes mellitus (T2DM) have become a major sanitary burden with an important economic impact. Novel treatment options have been designed with the aim of reducing the numerous complications associated with these metabolic disorders, as well as reducing morbidity and mortality and improving the quality of life of those who suffer from these disorders. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are among the most modern therapeutics that target ‘diabesity’, a term used to describe the pathophysiological link between obesity and T2DM. Their glucose-lowering effects are mainly attributed to glucose-dependent insulin secretion, glucagon inhibition and decreased gastric emptying. Given the effects on the central nervous system, GLP-1 RA usage may lead to body weight reduction. GLP-1 RAs are classified based on their pharmacokinetic properties as short- and long-acting agents, with both types being administered by subcutaneous injection. The latest agent from this drug class approved for use in T2DM is semaglutide, a long-acting compound that is the only GLP-1 RA available as an oral pill. The present narrative review highlights the most recently published data on the effects and safety of semaglutide in diabetic obesity, also emphasizing its cardiovascular benefits and potential side effects. In addition, an overview of the role of semaglutide in the treatment of non-diabetic obesity is provided.

Real-world evaluation of weekly subcutaneous treatment with semaglutide in a cohort of Italian diabetic patients

“…The efficacy of OW semaglutide as monotherapy or as add-on therapy has been extensively investigated in the Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes (SUSTAIN) program, which comprises ten clinical trials that compared OW semaglutide to placebo or other antidiabetic treatments. Results showed a robust reduction in HbA1c up to 1.5–1.8%, a reduction in major adverse CV events (CVE) rates, kidney prevention and weight loss in patients treated with OW semaglutide as compared to placebo or other treatments [ 17 – 20 ]. Existing clinical trial data suggest a combined effect of OW semaglutide on the dual target of glucose and obesity control, implying a particular advantage for diabetic patients with obesity.…”

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“…Consequently, there is a need for a practical, efficient and secure therapy for obesity and associated metabolic disorders in order to reduce mortality and improve quality of life [70]. Since several commonly used antidiabetic drugs, including sulfonylureas and insulin, may cause weight gain and so create a vicious circle, managing "diabesity" can be difficult [71]. A highly effective class of medicaments for type 2 DM is represented by the Glucagon-Like Peptide-1 (GLP-1) receptor agonist (RA) [8].…”

“…Exenatide, the first GLP-1 RA received approval in June 2005. Since then there are several other injectable agents available in the treatment of DM and obesity such as the shortacting formulation lixisenatide and exenatide and the longer-acting-formulation liraglutide, once-weekly extended-release dulaglutide, semaglutide and exenatide [21,71]. Tirzepatide is a novel and the first dual association between a GLP-1 and a Glucose-dependent Insulinotropic Peptide (GIP) RA recommended in obese patients, administered subcutaneously once weekly, which provides consistent and persistent reductions in body weight [25].…”

Efficacy and safety of SGLT-2i in overweight/obese, non-diabetic individuals: a meta-analysis of randomized controlled trials

“…Obesity control guidelines recommend lifestyle interventions and medication for the overweight population [5]. So far, only four kinds of anti-obesity drugs (orlistat, phentermine/topiramate, naltrexone/bupropion, and liraglutide/semaglutide) have been approved by the US Food and Drug Administration for sustained weight management [5,6]. The effectiveness of orlistat, phentermine/topiramate, and naltrexone/bupropion is limited, the safety is unknown, and the use cycle is long.…”

“…The effectiveness of orlistat, phentermine/topiramate, and naltrexone/bupropion is limited, the safety is unknown, and the use cycle is long. According to the limited data available, some glucagon-like peptide 1 receptor agonists (liraglutide/semaglutide) can lead to good weight loss and have high safety [6]. At present, more efforts are being made to seek new anti-obesity drugs with higher efficacy and more assured safety.…”