Semaglutide – GLP-1 Analog for Research on Glycemic Control and Weight Management
Semaglutide is a GLP-1 receptor agonist (glucagon-like peptide-1) developed to modulate glycemic homeostasis and energy balance. It is a peptide analog of human GLP-1 with an extended half-life, achieved through binding to albumin, which slows its degradation. By selectively activating the GLP-1 receptor, semaglutide enhances glucose-dependent insulin secretion, inhibits glucagon release, slows gastric emptying, and increases satiety, thereby contributing to improved glycemic control and body weight reduction.
From a pharmacological standpoint, semaglutide is the active ingredient in Ozempic (for type 2 diabetes), Wegovy (for chronic weight management), and Rybelsus (oral formulation). These formulations share the same mechanism of action but differ in dosage, indications, and route of administration. Weekly injections allow for gradual titration and improved therapeutic adherence, while the oral formulation enables studies on metabolism and systemic absorption.
Clinical Efficacy and Experimental Findings
In the major clinical trials of the STEP series (Semaglutide Treatment Effect in People with Obesity), conducted on individuals with overweight or obesity, treatment with semaglutide 2.4 mg resulted in an average weight loss of approximately 15% over 68 weeks compared to placebo. This weight reduction was accompanied by significant improvements in waist circumference, plasma lipid levels, blood pressure, and cardiovascular function. These findings, observed even in the absence of diabetes, confirm the drug’s impact on appetite regulation and energy metabolism.
In the treatment of type 2 diabetes mellitus, semaglutide improves glycemic control and lowers HbA1c levels without increasing the risk of hypoglycemia, thanks to its glucose-dependent mechanism of action. In addition to enhancing insulin secretion, it promotes a reduction in body weight and visceral fat mass, with a safety profile that is favorable compared to many other oral and injectable antidiabetic agents.
Comparison with Other Incretin Agonists
Semaglutide belongs to the class of GLP-1 receptor agonists, alongside newer molecules such as tirzepatide and retatrutide. While they all share activation of the GLP-1 receptor, these compounds differ in the number of hormonal receptors involved and the intensity of their metabolic effects. Comparative studies have shown that tirzepatide, which also acts on the GIP receptor, produces greater weight loss and glycemic improvement than semaglutide, whereas retatrutide, still under investigation, exhibits triple receptor activation (GLP-1, GIP, and glucagon) and an enhanced anabolic-metabolic effect.
Comparison with Other Incretin Agonists
Tirzepatide belongs to the same pharmacological class as Semaglutide and the newer Retatrutide, but differs in the number of receptors activated and the intensity of the metabolic effect. Comparative studies have shown that Tirzepatide outperforms Semaglutide in improving glycemic control and achieving greater weight reduction, as demonstrated in the SURPASS-2 (NEJM 2021) trial.
| Drug | Activated Receptors | Main Effects | Average Weight Loss (Clinical Data) |
|---|---|---|---|
| Semaglutide | GLP-1 | Satiety, slower gastric emptying, glycemic control | ≈ 15% in 68 weeks |
| Tirzepatide | GLP-1 + GIP | Dual action on appetite, glucose, and lipid metabolism | ≈ 22,5% in 72 weeks(SURMOUNT-1) |
| Retatrutide | GLP-1 + GIP + glucagon | Higher energy expenditure and fat oxidation | ≈ 24% in 48 weeks(Phase 2, preliminary data) |
Safety Profile and Tolerability
The most common side effects of semaglutide are gastrointestinal, including nausea, vomiting, diarrhea, or constipation, which are generally transient and dose-dependent. Gradual dose escalation helps reduce these symptoms. Regulatory data report rare cases of pancreatitis and cholelithiasis, as well as a possible worsening of diabetic retinopathy in predisposed patients. The drug is contraindicated in individuals with a history of medullary thyroid carcinoma or MEN2 syndrome, consistent with other molecules in the GLP-1 class.
Role in Research and Future Perspectives
Semaglutide has opened new perspectives in research on energy metabolism and weight control, serving as a reference model for the development of future multifunctional incretin agonists. Ongoing studies are exploring its potential applications in areas such as cardiovascular health, neuroprotection, and metabolic longevity. Multi-receptor combinations (GIP/GLP-1 and GIP/GLP-1/glucagon) are showing even more promising results, yet semaglutide remains one of the most well-documented treatments in terms of long-term efficacy and safety.
Note: The information provided is intended for descriptive and research purposes only. The clinical use of semaglutide must be evaluated and monitored by qualified healthcare professionals in accordance with official guidelines and product information sheets.
