Description
Semaglutide is a derivative of the naturally occurring GLP-1, a peptide known to lower blood sugar levels and enhance insulin secretion. Research shows that Semaglutide may also improve heart, liver, and lung function while helping to slow or prevent the effects of Alzheimer’s disease. Semaglutide has been shown to significantly decrease appetite by delaying gastric emptying and reducing intestinal motility. Glucagon-Like Peptide-1 (GLP-1) Analog Shown to Stimulate Insulin and Suppress Glucagon Secretion in a Glucose-Dependent Manner.
AOD9604 is a modified version of the hGH fragment 176-191 peptide (contains a di-sulfide bridge) and thus a derivative of human growth hormone (hGH). Originally developed as a lipolytic (fat burning) compound, AOD9604 has shown benefit in studies of heart disease, osteoarthritis/cartilage repair, and metabolic syndrome. AOD9604 stimulates lipolysis (the breakdown or destruction of fat) and inhibits lipogenesis in animal studies.
Properties
Semaglutide
- Chemical Formula: C187H291N45O59
- Molecular Mass: 3297.6g/mol
- Synonyms: Glucagon-like peptide 1 89750-14-1 GLUCAGON-LIKE PEPTIDE I FRAGMENT 7-36 AMIDE HUMAN
- CAS Number: 910463-68-2
- PubChem: 16135499
- Total Amount of the Active Ingredient: 2 mg (1 vial)
- Shelf Life: 36 months
AOD-9604
- Chemical Formula: C78H123N23O23S2
- Molecular Mass: 1815.12g/mol
- Synonyms: AOD-9604; AOD 9604; AOD9604
- CAS Number: 221231-10-3
- PubChem: 16131447
- Total Amount of the Active Ingredient: 2 mg (1 vial)
- Shelf Life: 36 months
Research Studies
Wegovy (semaglutide): a new weight loss drug for chronic weight management
Abstract
Obesity is a growing epidemic within the USA. Because weight gain is associated with an increased risk of developing life-threatening comorbidities, such as hypertension or type 2 diabetes, there is great interest in developing non-invasive pharmacotherapeutics to help combat obesity. Glucagon-like peptide-1 (GLP-1) receptor agonists are a class of antidiabetic medications that have shown promise in encouraging glycemic control and promoting weight loss in patients with or without type 2 diabetes. This literature review summarizes and discusses the weight loss results from the SUSTAIN (Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes), PIONEER (Peptide Innovation for Early Diabetes Treatment), and STEP (Semaglutide Treatment Effect in People with Obesity) clinical trial programs. The SUSTAIN and PIONEER clinical trials studied the use of 1.0 mg, once-weekly, subcutaneous and oral semaglutide (a new GLP-1 homolog), respectively, on participants with type 2 diabetes. The STEP trial examined the effects of 2.4 mg, once-weekly, subcutaneous semaglutide on patients with obesity. Trial data and other pertinent articles were obtained via database search through the US National Library of Medicine Clinical Trials and the National Center for Biotechnology Information. All three clinical trials demonstrated that semaglutide (injected or oral) has superior efficacy compared with placebo and other antidiabetic medications in weight reduction, which led to Food and Drug Administration approval of Wegovy (semaglutide) for weight loss.
Abstract
The glucagon-like peptide-1 receptor agonist (GLP-1RA) semaglutide is the most recently approved agent of this drug class, and the only GLP-1RA currently available as both subcutaneous and oral formulation. While GLP-1RAs effectively improve glycemic control and cause weight loss, potential safety concerns have arisen over the years. For semaglutide, such concerns have been addressed in the extensive phase 3 registration trials including cardiovascular outcome trials for both subcutaneous (SUSTAIN: Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes) and oral (PIONEER: Peptide InnOvatioN for the Early diabEtes tReatment) semaglutide and are being studied in further trials and registries, including real world data studies. In the current review we discuss the occurrence of adverse events associated with semaglutide focusing on hypoglycemia, gastrointestinal side effects, pancreatic safety (pancreatitis and pancreatic cancer), thyroid cancer, gallbladder events, cardiovascular aspects, acute kidney injury, diabetic retinopathy (DRP) complications and injection-site and allergic reactions and where available, we highlight potential underlying mechanisms. Furthermore, we discuss whether effects are specific for semaglutide or a class effect. We conclude that semaglutide induces mostly mild-to-moderate and transient gastrointestinal disturbances and increases the risk of biliary disease (cholelithiasis). No unexpected safety issues have arisen to date, and the established safety profile for semaglutide is similar to that of other GLP-1RAs where definitive conclusions for pancreatic and thyroid cancer cannot be drawn at this point due to low incidence of these conditions. Due to its potent glucose-lowering effect, patients at risk for deterioration of existing DRP should be carefully monitored if treated with semaglutide, particularly if also treated with insulin. Given the beneficial metabolic and cardiovascular actions of semaglutide, and the low risk for severe adverse events, semaglutide has an overall favorable risk/benefit profile for patient with type 2 diabetes.
Abstract
Aim: The aim of this trial was to investigate the mechanism of action for body weight loss with semaglutide.
Materials and methods: This randomised, double-blind, placebo-controlled, two-period crossover trial investigated the effects of 12 weeks of treatment with once-weekly subcutaneous semaglutide, dose-escalated to 1.0 mg, in 30 subjects with obesity. Ad libitum energy intake, ratings of appetite, thirst, nausea and well-being, control of eating, food preference, resting metabolic rate, body weight and body composition were assessed.
Results: After a standardised breakfast, semaglutide, compared with placebo, led to a lower ad libitum energy intake during lunch (-1255 kJ; P < .0001) and during the subsequent evening meal ( P = .0401) and snacks ( P = .0034), resulting in a 24% reduction in total energy intake across all ad libitum meals throughout the day (-3036 kJ; P < .0001). Fasting overall appetite suppression scores were improved with semaglutide vs placebo, while nausea ratings were similar. Semaglutide was associated with less hunger and food cravings, better control of eating and a lower preference for high-fat foods. Resting metabolic rate, adjusted for lean body mass, did not differ between treatments. Semaglutide led to a reduction from baseline in mean body weight of 5.0 kg, predominantly from body fat mass.
Conclusion: After 12 weeks of treatment, ad libitum energy intake was substantially lower with semaglutide vs placebo with a corresponding loss of body weight observed with semaglutide. In addition to reduced energy intake, likely mechanisms for semaglutide-induced weight loss included less appetite and food cravings, better control of eating and lower relative preference for fatty, energy-dense foods.
Abstract
Objective: To observe the chronic effects of human growth hormone (hGH) and AOD9604 (a C-terminal fragment of hGH) on body weight, energy balance, and substrate oxidation rates in obese (ob/ob) and lean C57BL/6Jmice. In vitro assays were used to confirm whether the effects of AOD9604 are mediated through the hGH receptor, and if this peptide is capable of cell proliferation via the hGH receptor. Method: Obese and lean mice were treated with hGH, AOD or saline for 14 days using mini-osmotic pumps. Body weight, caloric intake, resting energy expenditure, fat oxidation, glucose oxidation, and plasma glucose, insulin and glycerol were measured before and after treatment. BaF-BO3 cells transfected with the hGH receptor were used to measure in vitro 125I-hGH receptor binding and cell proliferation. Results: Both hGH and AOD significantly reduced body weight gain in obese mice. This was associated with increased in vivo fat oxidation and increased plasma glycerol levels (an index of lipolysis). Unlike hGH, however, AOD9604 did not induce hyperglycaemia or reduce insulin secretion. AOD9604 does not compete for the hGH receptor and nor does it induce cell proliferation, unlike hGH. Conclusions: Both hGH and its C-terminal fragment reduce body weight gain, increase fat oxidation, and stimulate lipolysis in obese mice, yet AOD9604 does not interact with the hGH receptor. Thus, the concept of hGH behaving as a pro-hormone is further confirmed. This data shows that fragments of hGH can act in a manner novel to traditional hGH-stimulated pathways.
Abstract
Both human GH (hGH) and a lipolytic fragment (AOD9604) synthesized from its C-terminus are capable of inducing weight loss and increasing lipolytic sensitivity following long-term treatment in mice. One mechanism by which this may occur is through an interaction with the beta-adrenergic pathway, particularly with the beta(3)-adrenergic receptors (beta(3)-AR). Here we describe how hGH and AOD9604 can reduce body weight and body fat in obese mice following 14 d of chronic ip administration. These results correlate with increases in the level of expression of beta(3)-AR RNA, the major lipolytic receptor found in fat cells. Importantly, both hGH and AOD9604 are capable of increasing the repressed levels of beta(3)-AR RNA in obese mice to levels comparable with those in lean mice. The importance of beta(3)-AR was verified when long-term treatment with hGH and AOD9604 in beta(3)-AR knock-out mice failed to produce the change in body weight and increase in lipolysis that was observed in wild-type control mice. However, in an acute experiment, AOD9604 was capable of increasing energy expenditure and fat oxidation in the beta(3)-AR knock-out mice. In conclusion, this study demonstrates that the lipolytic actions of both hGH and AOD9604 are not mediated directly through the beta(3)-AR although both compounds increase beta(3)-AR expression, which may subsequently contribute to enhanced lipolytic sensitivity.
Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone
Abstract
A synthetic analogue (AOD9604) of the lipolytic domain of human growth hormone (hGH) has been studied for its metabolic actions in obese Zucker rats. Daily treatment with an oral dose of AOD9604 of 500 microg/kg body weight for 19 days reduced over 50% (15.8 +/- 0.6 vs. 35.6 +/- 0.8 g) body weight gain of the animals in comparison with the control. The adipose tissues of the AOD9604–treated animals were found to have an increase in lipolytic activity. In contrast to chronic treatment with intact hGH, chronic treatment with AOD9604 showed no adverse effect on insulin sensitivity of the animals, as demonstrated with euglycemic clamp techniques. The results in the present study suggest that the analogue of the hGH lipolytic domain may have the potential to be developed into an orally usable and safe therapeutic agent for obesity.
Disclaimer
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The products offered on this website are intended for in-vitro studies only. In-vitro studies (Latin: “in glass”) are performed outside the body. These products are not medicines or drugs and have not been approved by the FDA to prevent, treat, or cure any medical condition, ailment, or disease. Bodily introduction of any kind into humans or animals is strictly forbidden by law.
