SEMAGLUTIDE (GLP-1) 20mg

Semaglutide (GLP-1)  — Research Overview

Introduction

Semaglutide is a long‐acting investigational GLP‐1 receptor agonist (GLP‐1RA) studied for its effects on glycemic control and body‐weight–related endpoints in controlled research settings. It is structurally engineered for prolonged exposure, enabling once‐weekly administration paradigms in experimental protocols [1–3].

Semaglutide is an acylated GLP‐1 analog with a C18 fatty‐diacid side chain attached via a spacer at Lys26, promoting albumin binding and enzymatic stability. This design extends half‐life to approximately one week and maintains high affinity and specificity for GLP‐1R. An oral co‐formulation has been developed using the absorption enhancer SNAC to facilitate transcellular uptake across the gastric epithelium under research conditions [1,4,5].

Chemical Characteristics

Other Known Titles: GLP‐1 analog; GLP‐1RA; (marketed forms include brand‐name products for approved indications)

Form: Lyophilized powder for reconstitution (research use)

Research Applications

1. Metabolic and Weight‐Related Research

– GLP‐1R activation has been investigated for effects on appetite, reduced energy intake, and body‐weight endpoints in multi‐week studies [2,6].

– Experimental designs assess dose–response, titration schedules, and durability of weight‐related outcomes over months [2,6].

2. Glycemic Control and Incretin Physiology

– GLP‐1R agonism modulates glucose‐dependent insulin secretion, suppresses glucagon when glucose is elevated, and reduces post‐prandial excursions [1–3].

– Research examines fasting/post‐prandial glucose, HbA1c trajectories, and β‐cell functional markers under standardized challenges [2,3].

3. Gastric Emptying and GI Motility

– GLP‐1R signaling can delay gastric emptying; semaglutide‐related changes are evaluated via scintigraphy, paracetamol tests, and meal‐tolerance protocols [3,7].

– Protocols commonly monitor GI adverse events (e.g., nausea) concurrent with motor effects during titration [2,3].

4. Cardiometabolic Markers and Outcomes

– Investigations include blood pressure, lipid panels, inflammatory markers, and composite cardiovascular outcomes in at‐risk cohorts [3,8].

– Study designs evaluate safety/tolerability and adjudicated events alongside metabolic efficacy [3,8].

5. Dosing, Pharmacokinetics, and Delivery

– Long half‐life supports once‐weekly subcutaneous administration in research; PK/PD models assess exposure–response and steady‐state dynamics [1–3].

– Oral semaglutide co‐formulated with SNAC enables gastric transcellular uptake; studies examine bioavailability, food‐timing effects, and dose proportionality [4,5].

6. Safety and Tolerability Under Research Conditions

– Commonly observed events include GI‐related signals during titration; protocols track labs and predefined stopping rules [2,3].

– Specific safety endpoints (e.g., retinopathy assessments, pancreatitis signals) are monitored in at‐risk cohorts per study design [3,8].

Conclusion

Semaglutide is a long‐acting GLP‐1 receptor agonist engineered for sustained exposure and studied for effects across glycemic control, appetite/weight regulation, and cardiometabolic parameters. Research includes once‐weekly subcutaneous and oral SNAC‐enabled formulations, with outcomes and safety characterized in controlled settings. Availability and use are limited to research applications; not for human or clinical use [1–8].

Semaglutide — References

• Knudsen, L. B., Nielsen, P. F., Huusfeldt, P. O., Johansen, N. L., Madsen, K., Pedersen, F. Z., Thøgersen, H., Wilken, M., & Agersø, H. Potent derivatives of glucagon-like peptide-1 with pharmacokinetic properties suitable for once daily administration. Journal of Medicinal Chemistry. 2000;43(9): 1664–1669.https://doi.org/10.1021/jm9909645
• Lau, J., Bloch, P., Schäffer, L., Pettersson, I., Spetzler, J., Kofoed, J., Madsen, K., Knudsen, L. B., McGuire, J., Steensgaard, D. B., Strauss, H. M., Gram, D. X., Knudsen, S. M., Nielsen, F. S., Thygesen, P., Reedtz-Runge, S., & Kruse, T. Discovery of the once-weekly GLP-1 receptor agonist semaglutide. Science Translational Medicine. 2015;7(327): 327ra27.https://doi.org/10.1126/scitranslmed.aab3071
• Marso, S. P., Bain, S. C., Consoli, A., Eliaschewitz, F. G., Jódar, E., Leiter, L. A., Lingvay, I., Rosenstock, J., Seufert, J., Warren, M. L., Woo, V., Hansen, O., Holst, A. G., Pettersson, J., Vilsbøll, T., & SUSTAIN-6 Investigators. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. The New England Journal of Medicine. 2016;375(19): 1834–1844.https://doi.org/10.1056/NEJMoa1607141
• Wilding, J. P. H., Batterham, R. L., Calanna, S., Davies, M., Van Gaal, L. F., Lingvay, I., McGowan, B. M., Rosenstock, J., Tran, M. T., Wadden, T. A., Wharton, S., Yokote, K., Zeuthen, N., Kushner, R. F., & STEP 1 Study Group. Once-weekly semaglutide in adults with overweight or obesity. The New England Journal of Medicine. 2021;384(11): 989–1002.https://doi.org/10.1056/NEJMoa2032183
• Davies, M. J., Bain, S. C., Atkin, S. L., Rossing, P., Scott, D., Shamkhalova, M., Bosch-Traberg, H., Syrén, A., & Seino, Y. Efficacy and safety of once-weekly semaglutide versus exenatide ER in subjects with type 2 diabetes (SUSTAIN 3): a 56-week, open-label, randomized clinical trial. The Lancet Diabetes & Endocrinology. 2018;6(4): 275–286.https://doi.org/10.1016/S2213-8587(18)30024-X
• Husain, M., Birkenfeld, A. L., Donsmark, M., Dungan, K., Eliaschewitz, F. G., Franco, D. R., Jeppesen, O. K., Lingvay, I., Mosenzon, O., Pedersen, S. D., Tack, C. J., Thomsen, M., Vilsbøll, T., Warren, M. L., Bain, S. C., & PIONEER 6 Investigators. Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes. The New England Journal of Medicine. 2019;381(9): 841–851.https://doi.org/10.1056/NEJMoa1901118
• Rubino, D., Abrahamsson, N., Davies, M., Hesse, D., Greenway, F. L., Jensen, C., Lingvay, I., Mosenzon, O., Rosenstock, J., Rubio, M. A., Rudofsky, G., Tadayon, S., Wadden, T. A., & Wilding, J. P. H. Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity: the STEP 4 randomized clinical trial. JAMA. 2021;325(14): 1414–1425.https://doi.org/10.1001/jama.2021.3224
• Frias, J. P., Davies, M. J., Rosenstock, J., Pérez Manghi, F. C., Fernández Landó, L., Bergman, B. K., Liu, B., & Cui, X. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. The New England Journal of Medicine. 2021;385(6): 503–515.https://doi.org/10.1056/NEJMoa2107519
• Granhall, C., Donsmark, M., Blicher, T. M., Golor, G., Søndergaard, F. L., Thomsen, M., & Anderson, T. W. Safety and pharmacokinetics of single and multiple ascending doses of the novel oral human GLP-1 analogue, semaglutide, in healthy male subjects. Diabetes, Obesity and Metabolism. 2019;21(1): 34–41.https://doi.org/10.1111/dom.13494
• Blundell, J., Finlayson, G., Axelsen, M., Flint, A., Gibbons, C., Kvist, T., & Hjerpsted, J. B. Effects of once-weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity. Diabetes, Obesity and Metabolism. 2017;19(9): 1242–1251.https://doi.org/10.1111/dom.12932

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