Role of glucagon-like peptide 1 receptor agonists in management of obesity.

Published data on the weight loss effects of glucagon-like peptide 1 (GLP-1) receptor agonists are reviewed, with a focus on data from clinical trials. Obesity is a significant health problem in the United States (an estimated 69% of U.S. adults are overweight and nearly 35% are obese), and few drugs have proven safety and efficacy as adjuncts to lifestyle modification for weight management. GLP-1 receptor agonists are used for glycemic control in patients with type 2 diabetes and have been studied for their weight loss effects in patients with and without diabetes; these agents produce weight loss benefits through their effects on satiety and gastric emptying. In December 2014, the liraglutide product Saxenda (Novo Nordisk) became the first GLP-1 receptor agonist approved by the Food and Drug Administration (FDA) for use in long-term weight management. Results of clinical trials that evaluated the effects of GLP-1 receptor agonist therapy on weight and body mass index indicated outcomes comparable or superior to those achieved with the use of other antiobesity agents. As a class, GLP-1 receptor agonists have a generally more favorable safety profile than several other antiobesity agents; transient, mild-to-moderate gastrointestinal symptoms were the most frequently reported adverse effects in clinical trials. Originally marketed for glycemic control in type 2 diabetes, GLP-1 receptor agonists have been found effective for weight reduction in patients with and without type 2 diabetes. Liraglutide is currently the only GLP-1 receptor agonist approved by FDA for obesity treatment.

Isaacs D ，Prasad-Reddy L ，Srivastava SB 《-》

GLP-1 receptor agonists for type 2 diabetes mellitus: recent developments and emerging agents.

More than 26 million people in the United States have type 2 diabetes mellitus (T2D). Many treatment options exist, but achieving long-term glycemic control in patients with T2D remains challenging. The glucagon-like peptide-1 receptor agonists (GLP-1 RAs) offer a treatment option that improves glycemic control and reduces weight, with a low risk of hypoglycemia. They have emerged as attractive options for the treatment of T2D, and significant advances and developments continue to be published regarding these agents. To identify relevant literature on emerging issues related to GLP-1 RAs, a search of the MEDLINE database was performed. Studies published in English evaluating the safety and efficacy of GLP-1 RAs were analyzed. Because of their advantages and unique mechanism of action, GLP-1 RAs are currently being studied in new clinical areas, including in combination with basal insulin, as adjunctive therapy in type 1 diabetes, and for weight loss. In addition, there are several emerging agents in development. Lixisenatide is a once-daily GLP-1 RA that targets postprandial glucose and may be most useful when added to basal insulin as an alternative to rapid-acting insulin. Albiglutide and dulaglutide are once-weekly GLP-1 RAs that may offer more convenient dosing. The most common adverse effects of all GLP-1 RA agents are gastrointestinal (e.g., nausea, diarrhea, and vomiting), but the rates of occurrence vary among agents. Due to the differences in pharmacokinetics, efficacy, rates of adverse effects, and administration requirements within the GLP-1 RA class, each agent should be evaluated independently. The future of GLP-1 RAs offers broader treatment options for T2D as well as potential in other treatment areas.

Trujillo JM ，Nuffer W 《-》

Glucagon-like peptide-1 receptor agonists and cardiovascular disease: from LEADER to EXSCEL.

Torekov SS 《-》

Weight Loss and Maintenance Related to the Mechanism of Action of Glucagon-Like Peptide 1 Receptor Agonists.

Ard J ，Fitch A ，Fruh S ，Herman L ... -  《-》

The Antiobesity Effect and Safety of GLP-1 Receptor Agonist in Overweight/Obese Patients Without Diabetes: A Systematic Review and Meta-Analysis.

Aim To determine the antiobesity effect and safety of glucagon-like peptide-1 receptor agonist (GLP-1RA) including liraglutide, exenatide and semaglutide treatment in overweight/obese patients without diabetes. The random-effect model was used to pool data extracted from included literatures. The weighted mean difference (WMD), odds ratio and 95% confidence interval (CI) were used to present the meta-analysis results (PROSPERO registration number: CRD 42020173199). The sources of intertrial heterogeneity, bias and the robustness of results were evaluated by subgroup analysis, sensitivity analysis and regression analysis, respectively. A total of 24 RCTs were recruited in the present analysis which included 5867 patients. The results showed that the treatment of overweight/obese patients without diabetes with GLP-1RAs including liraglutide, exenatide and semaglutide significantly achieved greater weight loss than placebo [WMD=-5.39, 95% CI (-6.82, -3.96)] and metformin [WMD=-5.46, 95% CI (-5.87, -5.05)]. The subgroup analysis showed that semaglutide displayed the most obvious antiobesity effect in terms of weight loss, the reduction of body mass index (BMI) and waist circumference (WC). However, GLP-1RAs treatments had more gastrointestinal adverse events (such as nausea and vomiting) than placebo and Met. The subgroup analysis also represented that semaglutide displayed the lowest risk of gastrointestinal adverse events among three kinds of GLP-1RAs. Our meta-analysis demonstrated that GLP-1RA had a superior antiobesity effect than placebo/Met in overweight/obese patients without diabetes in terms of body weight, BMI, and WC, especially for semaglutide, which had more obvious antiobesity effect and lower GI adverse events than liraglutide and exenatide.

Guo X ，Zhou Z ，Lyu X ，Xu H ，Zhu H ，Pan H ，Wang L ，Yang H ，Gong F ... -  《-》