Dimitar Marinov, Ph.D.Looking for information on how liraglutide works?
Look no further as we explore the scientific mechanisms behind the benefits of liraglutide for weight loss, glycemic control, and more.
In this guide, we take a closer look at the pharmacodynamics of the peptide to better understand the molecular mechanisms that drive its effects.
When planning on conducting research with liraglutide, this guide will provide the necessary insights to successfully run research experiments.
Plus, we include details about our preferred supplier of research-grade liraglutide and a range of other high-purity peptides and research chemicals.
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What is Liraglutide?
Liraglutide is a peptide medication that is approved by the United States Food and Drug Administration (FDA) to treat type 2 diabetes (T2D) and chronic weight management. It belongs to the class of drugs known as GLP-1 receptor agonists, which mimic the effects of the incretin hormone glucagon-like peptide 1 (GLP-1) [1].
This hormone is naturally found in the human body and helps to regulate blood sugar levels. Liraglutide is 97% homologous to GLP-1 (7-37)—the active form of the hormone, allowing it to bind to GLP-1 receptors throughout the body [2].
The only differences between liraglutide and GLP-1 are the addition of palmitate via a spacer glutamic acid residue to the amino acid lysine at position 26 and the replacement of lysine with arginine at position 34. These modifications increase the half-life of liraglutide to up to 13 hours, allowing for once-daily administration [3].
Liraglutide was first discovered in 1990 and was approved by the FDA to treat T2D under the brand name Victoza in 2010. The drug is also available by prescription under the brand name Saxenda. Both Victoza and Saxenda are registered trademarks of Danish pharmaceutical company Novo Nordisk [4, 5].
Victoza has also been approved for lowering cardiovascular risk in patients with T2D [6]. Additionally, a higher dosage of liraglutide under the brand name Saxenda has been approved for chronic weight management.
It was first approved in adults with a BMI over 30 kg/m2 or a BMI of 27 kg/m2 and at least one weight-related comorbidity, and later in obese adolescents aged 12-17 [7, 8].
Currently, liraglutide is also being studied for its potential use in other conditions, such as nonalcoholic fatty liver disease, psoriasis, polycystic ovary syndrome, and neurodegenerative diseases [9, 10, 11, 12, 13].
Mechanism of Action | How Liraglutide Works
Liraglutide exerts its benefits by activating the GLP-1 receptors, which are widely distributed throughout different organs in the human body, including the pancreas, gastrointestinal tract, central nervous system, and white adipose tissue [14].
By activating the GLP-1 receptors, liraglutide triggers complex mechanisms that improve glycemic control, body composition, among other processes.
How Liraglutide Works for T2D
LIraglutide improves glycemic control in type 2 diabetes by activating the GLP-1 receptors in the pancreas, gut, and adipose tissue.
The primary mechanism is its effect on the pancreas, as liraglutide activates the insulin-producing beta cells and suppresses the glucagon-producing alpha cells [15].
This mechanism allows the body to produce more insulin and less glucagon, which results in the lowering of blood sugar. The increase in insulin also suppresses gluconeogenesis in the liver.
Studies report that liraglutide improves fasting blood sugar as well as long-term glycemic control when assessed via HbA1C [16].
It's important to note that the effect of GLP-1 on the pancreas is glucose-dependent; thus, liraglutide does not increase insulin secretion if blood sugar levels are already normal. This helps reduce the risk of hypoglycemia in T2D patients.
Liraglutide may also help reduce the peak in blood sugar levels that may occur during the first couple of hours after a meal. It has been shown to temporarily slow down postprandial gastric emptying by up to 23% [17].
This effect occurs due to the activation of GLP-1 receptors in the gut. As a result, liraglutide may help to prevent excessive spikes and rapid changes in blood sugar that otherwise complicate glycemic control in T2D.
Some researchers also suggest that liraglutide may increase the capacity of fat cells for storing lipids by activating the GLP-1 receptors in adipose tissue. This could potentially decrease ectopic lipid accumulation and serum triglyceride levels, which may result in improved insulin sensitivity and glycemic control in T2D [18].
How Liraglutide Works for Weight Loss
Liraglutide works for weight management via the GLP-1 receptors found in the brain, the gut, and in adipose tissue.
Research by Ard et al. (2021) revealed that a key mechanism by which liraglutide contributes to weight loss is appetite suppression, via its binding to GLP-1 receptors in the hypothalamus, particularly in regions that control appetite [19].
This action activates the so-called POMC/CART (proopiomelanocortin and cocaine- and amphetamine-regulated transcript) neurons. Some of the major functions of these neurons are increased feelings of satiety and decreased hunger [20].
Liraglutide also indirectly suppresses the release of appetite-stimulating peptides such as NPY (neuropeptide Y) and AgRP (agouti-related peptide). This further enhances the hunger-suppressing effects of liraglutide.
Ard et al. also reported that liraglutide therapy is associated with higher levels of another satiety-promoting hormone called peptide YY (PYY), which signals fullness to the brain and reduces appetite [19].
This effect is likely due to liraglutide’s activation of GLP-1 receptors in the gastrointestinal system, as PYY is primarily produced in the gut.
As previously noted, the activation of GLP-1 receptors in the gut also slows gastric emptying within the first few hours after a meal. This may also contribute to the occurrence of early satiety while eating and reduced energy intake [17].
By activating GLP-1 receptors in adipose tissue, liraglutide may also help maintain adequate leptin production by fat cells during weight loss.
Additionally, liraglutide has been found to partially prevent the reduction of the satiety hormone leptin during weight loss, possibly by interacting with GLP-1 receptors in adipose tissue. Leptin is produced by adipose tissue and decreases during fat loss. This makes liraglutide particularly attractive as a long-term weight loss intervention [21].
How Liraglutide May Work to Reduce Inflammation
Studies suggest that liraglutide may have anti-inflammatory effects, which mediate some of the observed benefits in patients with obesity, psoriasis, neurodegenerative diseases, and others.
One clinical study involving 15 obese patients with T2D reported that liraglutide can inhibit the proinflammatory NF-kB pathway by increasing SIRT1 expression.
The researchers found that the mRNA expression of several proinflammatory factors and genes, including cytokines (TNF-α), extra- and intracellular receptors (TLR2, TLR4), and inflammation markers such as ceruloplasmin and SIRT1 expression, decreased after six weeks of treatment. The anti-inflammatory effects of liraglutide persisted even after the medication was stopped for another six weeks [22].
Research in T2D patients with psoriasis also reported significant inhibition of the expression of inflammatory factors such as IL-23, IL-17, and TNF-α, which was associated with a significant improvement in skin lesions [23].
Liraglutide may also help reduce inflammation in the central nervous system, with research suggesting that it has potential in conditions like Alzheimer's, Parkinson's, and multiple sclerosis management.
For example, animal studies suggest that liraglutide may reduce neuroinflammation in Parkinson's disease (PD) by suppressing the AMPK/NF-κB signaling pathway. Research in murine models of multiple sclerosis has also revealed that the peptide can reduce inflammation and slow down the demyelination of brain cells [12, 24].
Benefits of Liraglutide
In this section, we break down the research on key liraglutide benefits like blood sugar management, weight control, and neuroprotection.
Liraglutide For Type 2 Diabetes
As mentioned, liraglutide is an FDA-approved therapy for individuals with T2D. A 2014 meta-analysis covering 11 studies reported that liraglutide significantly lowers glycated hemoglobin, fasting plasma glucose, and blood pressure compared to placebo [25].
Moreover, liraglutide has been linked to a reduced risk of T2D complications such as heart disease and stroke. In the LEADER trial, researchers demonstrated that liraglutide reduces the risk of cardiovascular events and death by 13% and all-cause mortality by 15% compared to placebo. The greatest reduction was in the risk of myocardial infarction, which liraglutide lowered by 40% [26].
Liraglutide For Weight Loss
The ability of liraglutide to suppress appetite and promote weight loss has led to its approval by the FDA for chronic weight management in both adolescents and adults [7, 8].
Recent literature reviews have also confirmed the weight loss effects of liraglutide, including a 2022 systematic review covering 14 randomized controlled trials. In that review, the researchers found that 3mg/daily liraglutide, administered over 20-56 weeks, resulted in about a 5kg (~11lb) greater weight loss and a 1.86 kg/m2 greater BMI reduction compared to placebo [27].
Researchers should also note a 2017 critical review reporting that 3mg/daily liraglutide for 20 weeks resulted in an average weight loss of 3.7-8.0 kg (~8-17.5 lbs) in individuals with a BMI greater than 30. Further, 73% of the participants lost at least 5% of their body weight, with 37% losing at least 10% of their body weight [28].
The Potential of Liraglutide for Neuroprotection
A notable example of research investigating the neuroprotective potential of liraglutide is the ELAD trial, which stands for “Evaluating Liraglutide in Alzheimer's Disease.”
In this 12-month randomized controlled trial (RCT), participants were treated with liraglutide, and the results showed improved cognitive function and MRI volume in both the temporal lobe and the whole cortex, indicating a potential benefit in the treatment of Alzheimer's [29].
Additionally, animal experiments suggest that liraglutide may have a neuroprotective effect in murine models of Parkinson's disease (PD) by activating PGC-1α to regulate mitochondrial biogenesis, dynamics, autophagy, and apoptosis in the substantia nigra—the area of the brain that is affected by PD [30].
Although these results are promising, further research is needed to evaluate the potential benefits of liraglutide in neurodegenerative disease settings.
Liraglutide Dosage and Administration
Liraglutide for research purposes is available as lyophilized powder, which requires reconstitution with bacteriostatic water before administration.
The recommended liraglutide dosage in laboratory settings varies depending on the research objectives and a range of other factors. Therefore, it is essential to look to published data as a reference for creating accurate dosing protocols.
Clinical trials provide the most valuable scientific data on liraglutide dosing. According to the research, the daily liraglutide dosage for T2D ranges from 0.6mg to 1.8mg, while the dosage for weight management is up to 3mg/day [31, 32].
Based on this data, here is a reference liraglutide dosing protocol for weight loss [28, 33]:
- Liraglutide Dose: Starting dose of 0.6mg/day at week one to minimize the risk of side effects. Increase dose to 1.2mg/daily at week two, 1.8mg/daily at week three, 2.4mg/daily at week four, and 3.0mg/daily at weeks five and beyond.
- Frequency: Once daily at a regular schedule.
- Study Duration: From 20 to 68 weeks at 3mg/daily.
- Notes: Subcutaneous injections only. Do not exceed daily liraglutide dose of 3mg.
Liraglutide Side Effects
Some of the most frequent side effects of liraglutide include gastrointestinal issues, such as nausea and constipation. These side effects are typically mild and tend to subside over the course of therapy [34].
Liraglutide may also cause a slight increase in heart rate, a higher incidence of headaches, and local reactions at the injection site.
More severe side effects of liraglutide are rare, but they can include pancreatitis and gallbladder disease. These side effects can manifest with abdominal pain, nausea, and vomiting. Liraglutide may also cause allergic reactions, which can range from mild to severe [35].
Animal studies have suggested an increased risk of thyroid cancer and other malignancies, but more research is needed to confirm or rule out these effects in humans [36].
Liraglutide may not be suitable for pregnant or breastfeeding research subjects, those with a history of pancreatitis, gallbladder disease, or thyroid tumors, and those with a family history of medullary thyroid carcinoma.
Where to Buy Liraglutide Online? | 2024 Edition
Researchers and laboratory professionals wishing to purchase liraglutide online are advised to buy liraglutide strictly from a reputable vendor that explicitly markets their products for research purposes only.
Buying from unverified vendors may pose risks in terms of product quality. Moreover, researchers need also to comply with all applicable laws and regulations on the purchase, administration, and disposal of liraglutide and other research materials.
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Bacteriostatic Water and Liraglutide
When conducting research on liraglutide, it is essential to have the right supplies to ensure proper handling and storage. One of the most important items needed is bacteriostatic water, which is essential for reconstituting the peptide and ensuring its stability.
In addition to bacteriostatic water, researchers will require a wide range of other essential supplies, including sterile vials, needles, syringes, and alcohol wipes.
While it can be a hinderance to research, having a properly stocked lab is essential to the study.
How Does Liraglutide Work? | Overall
Liraglutide is a peptide medication approved for treating T2D and chronic weight management. It belongs to the GLP-1 receptor agonist class of drugs and thus mimics the effects of the incretin hormone GLP-1.
By activating GLP-1 receptors in different organs, liraglutide triggers complex mechanisms that improve glycemic control and body composition in research subjects.
Liraglutide improves glycemic control in T2D by increasing insulin, reducing glucagon, delaying gastric emptying, and suppressing gluconeogenesis.
It also works for weight management by regulating the appetite centers in the brain, stimulating endogenous peptides that promote satiety, and suppressing those that promote hunger.
To buy liraglutide online for research, we recommend the vendor with the purest peptides and most secure buying experience on the market.
Luis Daniel López Murillo, PhD