Semaglutide Peptides for Weight Management and Appetite Control

by | Nov 27, 2022 | Research

 

Semaglutide is a peptide and a prescription medication available in both US and EU for managing type 2 diabetes and obesity.

The medication is an agonist to the glucagon-like peptide-1 (GLP-1) receptors in the pancreas, the brain, and other organs. The effects of the drug are similar to GLP-1, a peptide hormone naturally produced by the intestines. It’s an incretin, meaning it stimulates insulin secretion.

Depending on the dosage, Semaglutide peptide can have different benefits, which range from reducing blood sugar levels and improving pancreatic beta cell function to suppressing appetite and supporting weight loss.

Semaglutide is also a subject of extensive research regarding other potential benefits, such as reducing pancreatic beta cell apoptosis and exhibiting neuroprotective properties.

Semaglutide for improved blood sugar control

Semaglutide was first approved in 2018 to manage high blood sugar in patients with type 2 diabetes.[1] It works by activating the GLP-1 receptors in the pancreatic beta cells, stimulating insulin synthesis and release.[2]

The stimulating effect on insulin synthesis is the primary mechanism via which Semaglutide lowers both fasting and postprandial glucose levels. 

A meta-analysis of 26 RCTs reveals that oral and injectable Semaglutide can effectively lower the fasting blood sugar levels and markers for long-term glucose control, such as HbA1c, in patients with type 2 diabetes.[3]

In addition to stimulating insulin secretion, Semaglutide reduces glucagon release and suppresses hepatic gluconeogenesis.[4] These effects are confirmed by studies in non-diabetic patients, which lasted up to 12 weeks and showed over 38% reduction in blood sugar levels compared to a placebo after a carbohydrate-rich breakfast.[5]

The researchers also report that Semaglutide effectively slowed down the speed of gastric emptying during the first hour after a meal compared to a placebo. 

The scientists suggested that this effect of Semaglutide may contribute to a more gradual release of glucose into the blood after a meal and better glycemic control. Yet, the overall speed of gastric emptying over the entire 5-hour monitoring period after the meal was not affected. 

A significant factor that helps Semaglutide stand out compared to other antidiabetic medications is that it can reduce hyperglycemia without causing hypoglycemia. 

The risk of hypoglycemia is not higher when compared to a placebo because Semaglutide stimulates insulin secretion in a glucose-dependent manner.[6] In addition, the inhibition of glucagon release also does not occur under hypoglycemic conditions.

 

Semaglutide for weight management and appetite control

Another significant advantage of Semaglutide over other medications for diabetes is that it stimulates insulin secretion without leading to weight gain. Most individuals with diabetes experience weight loss while taking the medication.

This is why Semaglutide is also officially approved as a chronic weight management medication for overweight or obese adults suffering from at least one weight-related condition.[7] Such conditions include hypertension, hyperlipidemia, metabolic syndrome, etc.

Studies show that Semaglutide significantly reduces ad libitum energy intake, which results in weight loss in the long term. In one trial, obese individuals lost 5 kg on average for 12 weeks without restricting their energy intake.[8]

Instead, Semaglutide injections reduced hunger and food cravings, improved control of eating, and reduced the patient’s preference for high-fat foods. This resulted in a 24% reduction in daily energy intake.

Semaglutide helps reduce hunger and cravings by activating the GLP-1 receptors in the brain, which play a major role in modulating appetite and reward-related behavior.[9]

Furthermore, the potential of Semaglutide to slow down gastric emptying within the first hour of having a meal may also contribute to a reduced ad libitum energy intake.

 

Stimulation of pancreatic beta cell survival and proliferation

Preliminary studies conducted in vitro and in test animals reveal that Semaglutide may stimulate pancreatic beta cells’ survival and proliferation.

These potential effects are of significant interest since patients with type 2 diabetes often suffer pancreatic beta cell dysfunction and apoptosis in the long term.[10]

Animal research suggests that Semaglutide may help reverse the harmful changes of obesity and insulin resistance on pancreatic beta cells and stimulate their proliferation.[11] It is important to note that human beta cells have a limited capacity to increase.

Researchers reveal that many in vitro studies also report that GLP-1 antagonists, such as Semaglutide, may protect pancreatic beta cells from apoptosis.[12] 

Several potential mechanisms are involved in the protective effect of Semaglutide, and one of the most prominent is reducing the overload on the endoplasmic reticulum of the beta cells in diabetic conditions. 

GLP-1 receptor activation may also help stimulate autophagy, which prevents beta cell injury and death by protecting against inflammation and oxidative stress.

Although many of these studies are in human islets, human studies are lacking, and the relevance of these mechanisms for type 2 diabetes patients remains to be proven. This is because technologies to assess in 3D the correct beta cell mass in vivo in humans are yet to be developed.

 

Semaglutide for the neuroprotective benefits

Interestingly, Parkinson’s disease and type 2 diabetes share several genetic susceptibilities, such as single nucleotide polymorphisms in the growth factor signaling kinase gene Akt.[13] This has sparked interest in researching the potential effects of diabetes medications for managing Parkinson’s disease.

Currently, other GLP-1 receptor agonists, such as Exendin-4, have already shown protective effects on Parkinson’s patients in phase II clinical trials. The benefits lasted up to 3 months after discontinuing the medication.[14]

Another GLP-1 antagonist, Liraglutide, is also currently being tested in a phase II trial in Parkinson’s patients.[16] 

The research regarding the potential neuroprotective effects of Semaglutide is still in its infancy, but many laboratory studies in animal models of PD show promising results.[15] The experiments report that Semaglutide has neuroprotective effects and increases the survival of the dopaminergic neurons, the apoptosis of which is associated with the development of Parkinson’s.

In animals, Semaglutide alleviated the chronic inflammatory responses in the brain, reduced lipid peroxidation, and increased the expression of growth factors that protect dopaminergic neurons in the substantia nigra and striatum.

Clinical trials investigating the potential neuroprotective effects of Semaglutide will soon follow and will explore the potential benefits of the medication outside of treating obesity and type 2 diabetes.

 

References:


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  16. Clinical trial identifier NCT02953665

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