Peripheral versus central effects of glucagon-like peptide-1 receptor agonists on satiety and body weight loss in Zucker obese rats

Recent years, glucagon-like peptide 1 receptor agonists (GLP-1RAs) have become central in the treatment of type 2 diabetes (T2D). In addition to their glucose-lowering properties with low risk of hypoglycaemia, GLP-1RAs reduce body weight and show promising results in reducing cardiovascular risk and renal complications in high-risk individuals with T2D. These findings have changed guidelines on T2D management over the last years, and GLP-1RAs are now widely used in overweight patients with T2D as well as in patients with T2D and cardiovascular disease regardless of glycaemic control. The currently available GLP-1RAs have different pharmacokinetic profiles and differ in their ability to improve glycaemia, reduce body weight and in their cardio- and renal protective potentials. Understanding how these agents work, including insights into their pleiotropic effects on T2D pathophysiology, may improve their clinical utilisation and be useful for exploring other indications such as non-alcoholic steatohepatitis and neurodegenerative disorders. In this review, we provide an overview of approved GLP-1RAs, their clinical effects and mode of actions, and we offer insights into the potential of GLP-1RAs for other indications than T2D. Finally, we will discuss the emerging data and therapeutic potential of using GLP-1RAs in combinations with other receptor agonists.

Download Full-text

Effect of Chronic Central Administration of Glucagon-Like Peptide-1 (7-36) Amide on Food Consumption and Body Weight in Normal and Obese Rats

Obesity Research ◽

10.1002/j.1550-8528.1998.tb00329.x ◽

1998 ◽

Vol 6 (2) ◽

pp. 147-156 ◽

Cited By ~ 43

Author(s):

Harry R. Davis ◽

Deborra E. Mullins ◽

Jesse M. Pines ◽

Lizbeth M. Hoos ◽

Constance F. France ◽

...

Keyword(s):

Body Weight ◽

Food Consumption ◽

Central Administration ◽

Obese Rats ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

Download Full-text

Effects of Glucagon-Like Peptide-1 Receptor Agonists on Body Weight: A Meta-Analysis

Experimental Diabetes Research ◽

10.1155/2012/672658 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8 ◽

Cited By ~ 34

Author(s):

Matteo Monami ◽

Ilaria Dicembrini ◽

Niccolò Marchionni ◽

Carlo M. Rotella ◽

Edoardo Mannucci

Keyword(s):

Body Weight ◽

Weight Reduction ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Pharmacological Interventions ◽

Receptor Agonists ◽

Cochrane Database ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

Glucagon-Like Peptide-1 receptor agonists (GLP-1RAs), approved as glucose-lowering drugs for the treatment of type 2 diabetes, have also been shown to reduce body weight. An extensive Medline, Cochrane database, and Embase search for “exenatide,” “liraglutide,” “albiglutide,” “semaglutide,” and “lixisenatide” was performed, collecting all randomized clinical trials on humans up to December 15, 2011, with a duration of at least 24 weeks, comparing GLP-1 receptor agonists with either placebo or active drugs. Twenty two (7,859 patients) and 7 (2,416 patients) trials with available results on body weight at 6 and 12 months, respectively, were included. When compared with placebo, GLP-1RAs determine a reduction of BMI at 6 months of −1.0 [−1.3; −0.6] kg/m2. Considering the average BMI at baseline (32.4 kg/m2) these data means a weight reduction of about 3% at 6 months. This result could seem modest from a clinical standpoint; however, it could be affected by many factors contributing to an underestimation of the effect of GLP-1RA on body weight, such as non adequate doses, inclusion criteria, efficacy of GLP-1RA on reducing glycosuria, and association to non-pharmacological interventions not specifically aimed to weight reduction.

Download Full-text