Liraglutide: An activator of the GLP-1 receptor with potential benefits

by | Mar 8, 2023 | Research

Liraglutide peptide is a synthetic analog of glucagon-like peptide-1 (GLP-1), and it was developed to activate the GLP-1 receptor, increasing insulin secretion, decreasing glucagon secretion, and slowing gastric emptying.  Liraglutide has the following sequence: H-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys(γ-Glu-palmitoyl)Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly-OH. The modification in Liraglutide peptide is the addition of a fatty acid chain (palmitic acid) to the amino acid lysine, in position 26 of the GLP-1 sequence. These modifications were made to enact a longer half-life and increase Liraglutide’s stability compared to GLP-1. Adding the fatty acid chain also appears to improve the binding of Liraglutide peptide to the GLP-1 receptor, enhancing its proposed therapeutic effects. The development of Liraglutide peptide was a significant advance in treating type 2 diabetes and obesity, and it has since become widely recognized for its potential to treat these conditions.

Liraglutide peptide was first developed in the 1990s, with the intention for use in combination with diet and exercise to improve blood sugar control in adults with type 2 diabetes. The development of Liraglutide was based on the discovery of the hormone glucagon-like peptide-1 (GLP-1), which is involved in regulating blood sugar levels in the body. It has been widely researched since its development, with some studies outlined below.


Liraglutide Peptide and Body Composition

Liraglutide peptide may have significant potential for weight loss, even in individuals who do not have type 2 diabetes. One study focused on obese and overweight participants who lost at least 5% of their initial weight during a low-calorie diet run-in.[1] The participants were randomly assigned to receive either Liraglutide peptide treatments or a placebo for 56 weeks, which appeared to lead to an additional 6 kg of weight loss on average for the study period. Liraglutide peptide also appeared to produce small improvements in some cardiovascular risk factors. The scientists reported that “From randomization to week 56, weight decreased an additional mean 6.2%  […] with liraglutide and 0.2% […] with placebo.

Another 56-week-long study of 846 patients reported similar results, with an average of 5-6% of observed weight loss in most participants.[2]

Researchers also suggested that combining Liraglutide peptide and exercise may lead to twice the weight loss compared to exercise alone.[3] One of the longest studies to investigate the effect of Liraglutide peptide on weight loss was a 20-week randomized, double-blind, placebo-controlled trial with a 2-year extension involving 564 overweight adults.[4] Participants received either once-daily administration of Liraglutide peptide, a placebo, or an open-label weight loss medication in addition to diet and exercise counseling. The study’s results suggested that Liraglutide peptide recipients lost more weight than those on a placebo or medication. Moreover, participants on Liraglutide also appeared to experience improvements in metabolic syndrome and blood pressure.


Liraglutide Peptide and the Endocrine System

Liraglutide peptide has some potential to act as an incretin in the endocrine system, specifically in the pancreas, which enhances insulin secretion. The peptide was developed to mimic the action of the incretin hormone GLP-1, which stimulates insulin secretion and reduces glucagon secretion in a glucose-dependent manner.[5] The effect appears to depend on the serum glucose levels, diminishing if the glucose is low and thereby preventing the occurrence of hypoglycemia.

When Liraglutide peptide is administered to people with type 2 diabetes, research studies suggest it may enhance the incretin effect by increasing GLP-1 levels in the bloodstream. This leads to increased insulin secretion and decreased glucagon secretion, resulting in improved blood sugar control. These studies reported apparently significant improvements in various parameters related to blood sugar control in patients with type 2 diabetes.[6] These included improved levels of glycated hemoglobin, body mass index (BMI), cardiovascular parameters, etc., all within the 3-6 months of the study. The scientists reported that the “meaningful difference in weight, body mass index, glycated hemoglobin (HbA1C), systolic blood pressure, and diastolic blood pressure from baseline to follow-up was -5.36 kg, -2.14 kg/m2, -1.76%, -12.38 mmHg, and 5.55 mmHg, respectively.” In addition, experiments observed that Liraglutide might also exhibit a protective effect on the function of the pancreas in type 2 diabetes patients and preserve the function of the beta cells, which normally produce insulin.[7]


Liraglutide Peptide and the Digestive System

Liraglutide peptide may slow down the emptying of food from the stomach into the small intestine, leading to a feeling of fullness and reduced appetite. Research studies suggest that 1-h gastric emptying was, on average, 23% lower in studies than placebo therapy, although that performance was dose-dependent.[8] Scientists observed that the speed of gastric emptying eventually returned to normal after 4 hours.

This proposed effect of Liraglutide peptide on slowing down gastric emptying may help in weight management and may also improve blood sugar control in people with diabetes. This is due primarily to slow stomach emptying, which naturally prolongs the feeling of fullness and helps reduce appetite. Furthermore, gastric emptying slows down the release of blood sugar after a meal, which helps improve glycemic control in diabetes patients.


Liraglutide Peptide and the Nervous System

Apart from slowing down gastric emptying, Liraglutide peptide has also been suggested by researchers to have the ability to suppress appetite by directly affecting the brain and its perception of hunger. This potential effect could be due to the peptide’s interaction with GLP-1 receptors in the brain, whose activation would lead to reduced appetite.[9] Liraglutide peptide has shown promise as a neuroprotective peptide in murine models of Parkinson’s Disease (PD)[10] with scientists suggesting that the peptide could reduce neuroinflammation and reduce neuron loss.

PD is a neurodegenerative disorder that affects the nervous system, particularly the dopaminergic neurons in the brain. While the exact cause of PD is unknown, some evidence suggests that an autoimmune reaction that destroys these neurons may contribute to the development of the disease. Liraglutide peptide is currently under active investigation in a phase II trial in PD patients (clinical trial identifier NCT02953665).



Liraglutide peptide has been widely researched for its potential to treat type 2 diabetes, obesity, and other conditions. However, ongoing research is also exploring the potential of Liraglutide in other areas. It has demonstrated great potential in research applications.

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  1. Wadden TA, Hollander P, Klein S, et al. Weight maintenance and additional weight loss with liraglutide after low-calorie-diet-induced weight loss: the SCALE Maintenance randomized study [published correction appears in Int J Obes (Lond). 2013 Nov;37(11):1514] [published correction appears in Int J Obes (Lond). 2015 Jan;39(1):187]. Int J Obes (Lond). 2013;37(11):1443-1451. doi:10.1038/ijo.2013.120
  2. Davies MJ, Bergenstal R, Bode B, et al. Efficacy of Liraglutide for Weight Loss Among Patients With Type 2 Diabetes: The SCALE Diabetes Randomized Clinical Trial [published correction appears in JAMA. 2016 Jan 5;315(1):90]. JAMA. 2015;314(7):687-699. doi:10.1001/jama.2015.9676
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