Semaglutide: GLP-1 Peptide for Diabetes & Weight

Semaglutide, which is also known as Ozempic, is a glucagon-like peptide 1 receptor (GLP-1) agonist that is used to help manage blood sugar levels for the treatment of type 2 diabetes (T2D) and to help with weight management. It is an effective weight reduction medication that works by imitating a hormone that makes you feel full, decreasing your appetite, and slowing down the emptying of your stomach. When paired with diet and exercise, this sustained action makes users feel full for a longer period of time, which helps them regulate their weight loss.

The structure of semaglutide is shown, with the GLP-1 protein at the top and the γ-glutamate linkers connected to the C18 stearic biacid spacer. The HSA (not illustrated) would be attached to the carboxylic acid group at the bottom of the C18 chain.

Semaglutide's Mechanism of Action: How This GLP-1 Agonist Works in The Body

As an agonist of the GLP-1 receptor, studies have shown that semaglutide has particular effects on the brain, stomach, pancreas, and small intestine. Here's a thorough explanation of how it affects each of these organs:

• The small intestine: Semaglutide amplifies the incretin effect, which is the release of hormones in reaction to food consumption. When nutrients are consumed, the small intestine releases more incretin hormones, such as GLP-1.

• Nutrient Absorption: Although semaglutide's main action is more connected to hormone production (glycemic control) than direct absorption processes, it may also indirectly suppress how nutrients are absorbed in the small intestine by intensifying the incretin effect.

• The stomach: Semaglutide slows down the process by which food passes from the stomach into the small intestine, a phenomenon known as gastric emptying. This prolongs feelings of fullness and can help cut back on overall food consumption, which can help with weight loss or managing obesity.

• Appetite Regulation: The speed at which the stomach empties its contents is one factor that regulates appetite signals, and the delay in gastric emptying affects these signals as well.

• Insulin Secretion: In reaction to elevated blood glucose levels, semaglutide causes the pancreatic beta cells to generate more insulin. This aids diabetics in lowering their blood sugar levels.

• Glucagon Suppression: When blood sugar levels are low, it also prevents the pancreatic alpha cells from secreting glucagon. Semaglutide's reduction of glucagon secretion, which normally raises blood sugar levels, contributes to a more stable blood glucose level.

• Appetite Control: Effects of semaglutide reduces hunger and calorie intake by influencing the brain's appetite centers. This action helps obese people regulate their weight. It improves the brain's satiety signals, which help regulate portion sizes and lower total food consumption while also promoting feelings of fullness.

Research: Clinical Evidence for Weight Loss and Diabetes Management

Research indicates that semaglutide is useful for weight reduction and can enhance cardiometabolic indicators. It is also linked to a decreased risk of diabetes and enhancements in physical function. 

Reduction of body mass

In the Semaglutide Treatment Effect in People With Obesity (STEP) studies, participants experienced an average weight reduction of 6% after 12 weeks and 12% after 28 weeks. In a practical trial, patients saw an average weight reduction of 10% over a period of 6 months. In a separate research, patients experienced an average weight reduction of 13.6% after receiving a maintenance dose of 1 mg, and 12.8% following a maintenance dose of 2 mg. In a longitudinal study, participants administered semaglutide experienced more weight loss compared to those receiving a placebo. 

Cardiometabolic indicators

A real-world investigation has shown that individuals administered semaglutide experienced a decrease in total cholesterol and triglycerides. In a separate trial, participants administered semaglutide showed enhancements in physical functioning scores. 

Security

In a particular trial, most adverse events were classified as mild to moderate and did not necessitate the cessation of treatment. Separate research indicated no elevated risk of thyroid problems in persons administered semaglutide compared to those receiving a placebo. 

Semaglutide in Clinical Practice: Applications for Obesity and Type 2 Diabetes

• Obesity management: The primary clinical research application of semaglutide involves examining its efficacy in facilitating substantial weight reduction in patients with obesity, frequently through extensive trials such as the "Semaglutide Treatment Effect in People with Obesity (STEP)" program. 

• Treatment for Type 2 diabetes: Semaglutide injection is being investigated in clinical studies as a potential therapeutic option for type 2 diabetes, assessing its efficacy in reducing blood glucose levels and managing cardiovascular risk factors linked to the condition. 

• Mode of action: Semaglutide acts as a glucagon-like peptide-1 receptor agonist, facilitating appetite regulation by enhancing satiety and diminishing hunger signals. 

• Dosage forms: Clinical research frequently investigates various dosages of semaglutide to ascertain the appropriate dosage for weight management and diabetic regulation. 

• Combination therapies: Research is underway to evaluate the effectiveness of semaglutide in conjunction with other pharmacological agents or lifestyle modifications for enhanced weight reduction and diabetes control. 

Semaglutide's Future: Emerging Research and Treatment Developments

Future studies on semaglutide may investigate its long-term safety, the best ways to utilize it, and how to tailor treatment for obesity.

• Factors that predict a response: Finding out what characteristics can predict how a patient would respond to semaglutide.

• Safety profile over the long term: Figuring out how safe it is to use semaglutide for a long time.

• Length of treatment: Deciding how long a patient should be on semaglutide. Interventions for lifestyle: Figuring out the most effective lifestyle changes to use together with semaglutide.

• Doses for maintenance: Figuring out the lowest doses of semaglutide that are most effective.

• The treat-to-target approach: Using semaglutide as part of a tailored approach to manage issues associated with weight.

References

1. Tilinca, M. C., Tiuca, R. A., Niculas, C., Varga, A., & Tilea, I. (2021). Future perspectives in diabesity treatment: Semaglutide, a glucagon‑like peptide 1 receptor agonist. Experimental and Therapeutic Medicine, 22(4), 1-11.

2. Bergmann, N. C., Davies, M. J., Lingvay, I., & Knop, F. K. (2023). Semaglutide for the treatment of overweight and obesity: a review. Diabetes, Obesity and Metabolism, 25(1), 18-35.

3. Papakonstantinou, I., Tsioufis, K., & Katsi, V. (2024). Spotlight on the Mechanism of Action of Semaglutide. Current Issues in Molecular Biology, 46(12), 14514-14541.

4. Williams, D. M., & Evans, M. (2020). Semaglutide: charting new horizons in GLP-1 analogue outcome studies. Diabetes Therapy, 11(10), 2221-2235.

5. Fallows, E., Ells, L., & Anand, V. (2023). Semaglutide and the future of obesity care in the UK. The Lancet, 401(10394), 2093-2096.