GLP-1 receptor agonists: an updated review of head-to-head clinical studies

Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are attractive options for the treatment of type 2 diabetes (T2D) because they effectively lower A1C and weight while having a low risk of hypoglycemia. Some also have documented cardiovascular benefit. The GLP-1 RA class has grown in the last decade, with several agents available for use in the United States and Europe. Since the efficacy and tolerability, dosing frequency, administration requirements, and cost may vary between agents within the class, each agent may offer unique advantages and disadvantages. Through a review of phase III clinical trials studying dulaglutide, exenatide twice daily, exenatide once weekly, liraglutide, lixisenatide, semaglutide, and oral semaglutide, 14 head-to-head trials were identified that evaluated the safety and efficacy of GLP-1 RA active comparators. The purpose of this review is to provide an analysis of these trials. The GLP-1 RA head-to-head clinical studies have demonstrated that all GLP-1 RA agents are effective therapeutic options at reducing A1C. However, differences exist in terms of magnitude of effect on A1C and weight as well as frequency of adverse effects.

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

“…Nausea occurred in 17.0%, diarrhea in 12.2% and vomiting in 6.4% of patients treated with semaglutide 0.5 mg. As for patients treated with semaglutide 1.0 mg, nausea occurred in 19.9%, diarrhea in 13.3% and vomiting in 8.4% of cases ( 66 , 67 ). Semaglutide has a similar gastrointestinal safety profile as other GLP-1 Ras ( 68 , 69 ). A metanalysis from 2018 that included nine phase III randomized controlled trials and 9,773 subjects highlighted that semaglutide did not increase the risk of any adverse events, hypoglycemia or pancreatitis, but had a higher risk of gastrointestinal reactions (mainly nausea, vomiting, diarrhea, abdominal discomfort and decreased appetite) when compared to other therapies [relative risk (RR)=1.98; P<0.001] ( 70 ).…”

A Review of Current Trends with Type 2 Diabetes Epidemiology, Aetiology, Pathogenesis, Treatments and Future Perspectives

“… 283 The reported varying impacts of different GLP-1R agonists on blood glucose levels, weight loss, cardiovascular outcomes and adverse effects should play an integral role when determining which agonist is best to administer to a patient depending on their medical requirements. 260 …”

“…These GLP-1 analogues are effective insulinotropic agents and successfully suppress glucagon secretion in a glucose-dependent manner. [260][261] GLP-1 analogues also induce weight loss, which is associated with improved T2D prognosis. 252,262,263 GLP-1R activity is thought to mediate weight loss by induction of satiety.…”

An Uncommon Case of Dulaglutide-Related Morbilliform Drug Eruption

“…Dulaglutide is a onceweekly injectable GLP-1 medication that has been shown to reduce hemoglobin A1c (HbA1c), body weight, and blood glucose levels among patients with type 2 diabetes [2]. Furthermore, in the Researching Cardiovascular Events With a Weekly Incretin in Diabetes (REWIND) trial, dulaglutide was shown to reduce the first occurrence of the 3-point major adverse cardiovascular events (MACE) composite outcome including stroke, and improve kidney function during a median follow-up of 5.4 years [3]. Side effects of dulaglutide are mainly gastrointestinal in nature, such as nausea and abdominal discomfort, and generalized cutaneous adverse reactions are extremely uncommon [4].…”