The 10+ Benefits of Liraglutide

An Anti-Obesity with Cognitive Enhancement

Liraglutide protects the brain, improves weight loss, and protects against many of the problems associated with metabolic syndromes.  

 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3411533/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3411533/

 

Basics

Liraglutide also goes by Saxenda and Victoza. R

Liraglutide 3.0 mg is currently approved for weight management in Australia, Canada, the European Union, Mexico and the USA. R

It has been proven safe in long term studies. R

It is a great alternative for diabetics afraid of using needles. R

It is being looked into as a replacement for bariatric surgeries such as gastric bypass surgery. R

A lot of its effects with diabetes, obesity and the brain are based on liraglutide's ability to change the composition of the gut microbiome. R

Benefits

1. Improves Type 2 Diabetes

 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3964023/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3964023/

 

Liraglutide can help control blood glucose. R

It can also reduce hyperglycemia, especially after meals (via enhanced insulin secretion, delaying gastric emptying and suppressing glucagon secretion) for up to 24 hours. R R R

Liraglutide, like other GLP1 analogues, will only work on glucose when it is introduced into the body, thus preventing hypoglycemia. R

It reduces fasting insulin and fasting glucose. R R

Liraglutide can protect the kidneys when exposed to high amounts of glucose and prevent the progression of diabetic kidney disease. R R

It also reduces hemoglobin A1c. R

In animals, it has shown to inhibit cell death and regenerate beta cells found in the pancreas. R

Liraglutide is even more effective when combined with metformin. R R

Switching from sitagliptin (DPP-4i) to liraglutide is usually not a problem for patients. R

Liraglutide can decrease many of the cognitive problems that are seen with diabetes. R

2. Fights Obesity

 
 

Liraglutide is FDA approved for treatment of obesity. R

Liraglutide can decrease appetite and caloric intake, while inhibiting weight gain. R R

It has also been shown to lower triglyceride levels and the oxidative stress from high LDL. R R

Liraglutide has also shown to help induce weight loss in obese patients with higher doses increasing the amount of total weight loss. R R

One way it does this is by inhibiting fat stem cells. R R

Women on average have a greater weight loss response then men. R

Liraglutide has shown to be synergistic with melatonin in helping lose weight. R 

It also decreases leptin, which is usually high obesity signaling leptin resistance, and increase leptin sensitiivty. R R

It can increase the conversion of white fat to brown fat. R R

3. Protects The Brain

 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4886514/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4886514/

 

In animal models, liraglutide can improve cognitive function. R

In stroke, liraglutide significantly decreases the damage size, improves neurologic deficits, and lowers stress-related hyperglycemia (also increasing expression of NeuN, GFAP, vWF, and GLP-1R). R R R

It can do this by lowering the amount of reactive oxygen species (ROS) in the brain and preventing glutamate-induced excitotoxicity. R R

It also crosses the blood brain barrier (BBB). R

Liraglutide can protect the brain from cerebral edema after traumatic brain injury (TBI) and can reduce BBB permeability. R

This makes liraglutide beneficial for patients with hemorrhagic strokeR

Liraglutide is also protective against Alzheimer's Disease and other dementias. R

In a mouse model of Alzheimer's liraglutide was able to increase memory and hippocampus size. R

It can also promote neurite outgrowth (via MEK-ERK pathway). R

Although, other studies have shown it has no effect on removing beta-amyloid plaque, but it can help prevent the buildup. R R

It can also prevent the toxic effects of beta-amyloid plaque on the brain. R

In diabetic mice, it has shown to prevent tau hyperphosphorylation. R R

Liraglutide may also help patients with Parkinson's Disease, although there is conflicting evidence. R R

When rats with Parkinson's were given liraglutide combined with sitagliptin, there was a reduction in brain damage and pro-inflammatory markers (IL1b, IL6, and TGFB1) with an increase in dopamine, GDNF, and TH+ cells. R

In epileptic mice, liraglutide can decrease the severity of seizures, reduce oxidative stress and restore altered neurotransmitter levels. R

4. Has Anti-Anxiety Properties

Liraglutide in animal models has shown to have anti-anxiety properties. R

It doesn't show as great of an anti-depressant action as sitagliptin. R

5. Has Anti-Inflammatory and Anti-Oxidant Properties

 
 

In vitro, liraglutide has anti-inflammatory effects on pancreatic cells. R

It's anti-inflammatory properties can protect diabetic rats after having pancreatic graft implants. R

Liraglutide decreases secretion of the pro-inflammatory cytokine IL-6 and chemokine CCL2. R

Liraglutide can reduce oxidative stress. R

It can decrease ROS and increase MnSOD (a powerful mitchondrial antioxidant). R

6. Protects The Vascular System

 
 

In the LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) 2 year study, liraglutide showed to decrease the chance of heart attack. R

Liraglutide directly can protect heart muscles (via regulation of calcium homeostasis). R

Lirglutide can also prevent the calcification of arteries and lower total cholesterol levels. R R

It can help with chronic kidney disease as liraglutide reduces the chance of atherosclerosis and kidney inflammation (but not fibrosis). R

Lirglutide can balance blood pressure. R

It can improve hypertension (high blood pressure) in polycystic ovarian sydnrome (PCOS). R

It can also protect against hypertension brought on by certain toxins. R

7. May Prevent Multiple Sclerosis

In rats susceptible to multiple sclerosis (MS), liraglutide was able to delay the onset of the disease. R

8. May Help With Addiction

When rats were given liraglutide, they cared less for alcohol and consumed less. (via attenuating dopamine release, but no effect on blood alcohol levels). R

This was also similar in cases with amphetamine-induced, cocaine-induced and nicotine-induced addictions. R

9. Protects the Liver

 
 

Liraglutide can protect the liver from excess inflammation. R

Liraglutide is able to decrease reduce metabolic dysfunction, lipotoxicity, and insulin resistance in patients with non-alcoholic steatohepatitis (NASH). R R 

In the LEAN (Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis study, liraglutide resolved NASH. R

It decreases leptin, increases adiponectin and reduces inflammatory markers like hsCRP. R

Hepatic de novo lipogenesis (DNL) is a major contributor to lipid accumulation in the context of Non-alcoholic fatty liver disease (NAFLD). R

Liraglutide can significantly reduce hepatic DNL. R

In vitro, it can reduce fatty tissue on the liver in NAFLD. R

Patients with metabolic problems can have high non-esterified fatty acids (NEFA) levels. R

Liraglutide is able to reduce fasting NEFA levels. R

It has no effect on gallbladder volume. R

10 May Help With Fatigue

Liraglutide use has been associated with reduction in daytime sleepiness. R

This is more of a benefit for those with type 2 diabetes, than healthy patients. R

Alternatives to Liraglutide

 
 

These will activate the same pathways and should serve as a replacement to liraglutide. 

Supplements:

Drugs:

  • Albiglutide R
  • Dulaglutide R
  • Exenatide R
  • Lixisenatide R
  • Semaglutide R

Click here for the full list of GLP1 receptor agonists and GLP1 increasers.

Caveats

Lirglutide may prevent bones from forming properly and may increase chances of osteoporosis and fractures. R

Although some studies have shown the opposite. R

Liraglutide may blunt some of the benefits of exercise. R

Lirglutide may increase the risk for thyroid cancers. R

Serum calcitonin, a biomarker of medullary thyroid cancer, can become slightly increased in some liraglutide patients. R

It's possible for GLP1 analogues, like Lirglutide to cause acute pancreatitis. R

It shouldn't be taken with other GLP1 receptor agonists. R

It shouldn't be taken with insulin. R

Serious side effects reported in patients include gallbladder disease, renal impairment, and suicidal thoughts. R

Less serious ones have been GI upset. R

It can raise heart rate (~2-3bpm higher). R

Liraglutide may also lower testosterone. R

Mechanism Of Action

 
https://www.ncbi.nlm.nih.gov/pubmed/25733821

https://www.ncbi.nlm.nih.gov/pubmed/25733821

 

Simple:

  • Increases ACTH and coritsol when taken acutely, but chronically taken lowers it R
  • Increases adenylate cyclase 3 (AC3) R
  • Increases adiponectin R
  • Increases AMPK R
  • Increases angiogenesis R
  • Increases Gastric inhibitory polypeptide (GIP) R
  • Increases GLP1 R
  • Increases intracellular ROS (decreases it extracellularly) R R
  • Increases manganese superoxide dismutase (MnSOD) R
  • Increases NO production R
  • Increases PI3K/AKT pathway R
  • Decreases CCL2 and IL-6 R
  • Decreases Leptin R
  • Decreases HbA1c (but dulaglutide may be more more effective) R R R
  • Decreases hsCRP R
  • Decreases mTOR R
  • Decreases NF-kB activation R
  • Decreases NPY/AgRP R
  • Decreases Orexin (possibly) R
  • Decreases PDGF R
  • Decreases PPARγ R
  • Decreases TGF-B R
  • Has low immunogenicity R

Advanced:

  • Liraglutide is an acylated analogue of GLP-1 (glucagon-like peptide-1) with an amino acid sequence 97% homologous to human hormone incretin GLP-1. R
  • GLP1 is secreted response to ingestion of carbohydrates and lipids, stimulating insulin secretion, suppression of glucagon secretion, slower gastric emptying and increased satiety. R
  • Liraglutide stimulates insulin secretion of the pancreas by binding to the same receptors as GLP1, when blood glucose is elevated. R
  • It's half-life is around 13 hours when injected subcutaenously, and when GLP1 is produced endogenously, it's half-life is of 1.5-2 minutes. R R
  • Receptors for GLP1 are found all over the body: pancreas, lung, kidney, atrial cardiomyocytes, lymphocytes, and the brain. R
  • DPP4 breaks down GLP1. R

Genetics

 
 
  • rs10305420
    • T allele - has worse response to liraglutide regarding weight loss in obese PCOS women R
  • rs6923761
    • A allele - had better response to liraglutide regarding weight loss in obese PCOS women R

More Research

  • Watch the MOA video and see how Victoza® works in multiple systems. V
  • Liraglutide blocks some of the effects of stem cells. R
  • Liraglutide protected mice from LPS-induced acute lung injury. R