High-Dose Once-Weekly Semaglutide: A New Option for Obesity Management

Abstract

Objective To review the pharmacology, efficacy, and safety of high-dose once-weekly semaglutide for chronic weight management. Data Sources PubMed/MEDLINE and ClinicalTrials.gov were searched (inception to September 8, 2021) using keywords “semaglutide” and “obesity,” “weight,” “high dose,” “high-dose,” or “2.4.” Study Selection and Data Extraction Clinical trials with published results were included. Publications studying the oral or <2.4 mg formulation of semaglutide were excluded. Data Synthesis Four phase 3, multicenter, randomized, double-blind trials demonstrated efficacy of high-dose once-weekly semaglutide compared with placebo for weight loss. Study populations included patients with overweight or obesity (STEP 1, STEP 3, and STEP 4) or patients with diabetes and with overweight or obesity (STEP 2). Lifestyle interventions for diet and exercise were included for all participants. Weight loss from baseline was significant for all studies, and secondary outcomes demonstrated cardiometabolic improvements including waist circumference, systolic blood pressure, and lipid profiles. Gastrointestinal adverse effects were common, but the medication was otherwise well tolerated. Relevance to Patient Care and Clinical Practice High-dose semaglutide offers significant weight-lowering potential and favorable effects on cardiometabolic risk factors and glycemic indices. Clinicians and patients should consider the route and frequency of administration, adverse effect profile, and cost when choosing an antiobesity medication. The importance of concomitant lifestyle interventions should be emphasized. Conclusions High-dose once-weekly semaglutide can significantly reduce weight, and although gastrointestinal adverse effects were common, it is generally well tolerated.

Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review

“…One limitation that could have impact on the inter-trial comparations is that the studies with and without diabetes were not well balanced regarding sex and race [ 27 ]. While the STEP 2 trail included 51% female participants [ 22 ], the STEP 1, STEP 3 and STEP 4 trials included 73%, 81% and 79% female participants, respectively [ 15 – 17 ].…”

Efficacy and Safety of Liraglutide and Semaglutide on Weight Loss in People with Obesity or Overweight: A Systematic Review

“…People with obesity or overweight have a severe impact on our physical health and lead to an increased incidence of various diseases, especially people with obesity or overweight and type 2 diabetes, which is often accompanied by complications such as cardiovascular disease. [1][2][3][4] GLP-1RA can bring us weight loss and achieve the effect of lowering blood sugar, reducing the death rate of Covid-19, 5 and has a protective effect on our cardiovascular. 11 The primary purpose of this study is to compare the efficacy and safety of two GLP-1RA for weight management (liraglutide and Semaglutide) that the FDA has approved and recommended in the 2022 American Diabetes Association's standards for diabetes care and provide evidence for individualized medication management in clinical practice.…”

“…Obesity is a chronic disease with serious health consequences; it can lead to insulin resistance, hypertension, and dyslipidemia, associated with complications such as type 2 diabetes, cardiovascular disease, and non-alcoholic fatty liver disease, and reduce life expectancy. [1][2][3][4] Recently, obesity has been associated with increased hospitalizations, the need for mechanical ventilation, and death in patients with coronavirus disease 2019 (Covid-19). 5,6 Weight loss of 5% to 10% has been shown to reduce obesityrelated complications and improve quality of life.…”

Tirzepatide versus semaglutide for weight loss in patients with type 2 diabetes mellitus: A value for money analysis

“…Over recent years, several pharmacological agents have been used as adjuncts for enabling weight loss, such as orlistat and naltrexone/bupropion combination, among others 13,14 . In addition, several GLP‐1RA, in particular semaglutide, have proven to be effective with relatively few side effects 3,15 16 .…”

“…13,14 In addition, several GLP-1RA, in particular semaglutide, have proven to be effective with relatively few side effects. 3,15 A recent study attempted to calculate quality-adjusted life years indirectly for glucagon-like peptide-1 agonists based on existing data and found that semaglutide was the most costeffective of the drugs tested. 16 Tirzepatide is first in a new drug class that also induces clinically relevant weight reduction.…”