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Key Benefits
Biologic Description
Semaglutide is a peptide that functions as a glucagon-like peptide-1 (GLP-1) analog. Its primary mechanism of action involves mimicking the actions of human incretin, a group of metabolic hormones. Semaglutide stands out from other GLP-1 agonists due to its resistance to degradation by the dipeptidyl peptidase-IV enzyme. This characteristic enhances its effectiveness in stimulating insulin secretion and reducing glucagon levels in a glucose-dependent manner, thereby effectively lowering both fasting and postprandial blood glucose levels.
This compound has gained notable attention through several key studies, exploring its impact on weight management, glycemic control, cardiovascular health, and even neuroprotection. Semaglutide has also been known by brand names such as Ozempic, Rybelsus, and Wegovy, and it carries an identifier code of A10BJ06.
One of the unique aspects of Semaglutide is its dual FDA approval for both oral and injectable use, making it a versatile option in treating type 2 diabetes (T2D) and chronic weight management in overweight or obese patients. Its efficacy stems from the fact that it is 94% homologous to the naturally occurring GLP-1, an incretin hormone released in the gastrointestinal tract after food intake. This similarity allows Semaglutide to maintain the physiological functions of GLP-1 while offering increased stability and a longer duration of action, which enhances its therapeutic potential.
In terms of safety, Semaglutide has a favorable profile but does carry risks, including gastrointestinal upset, a potential link to thyroid C-cell tumors in rodent studies, contraindication in Multiple Endocrine Neoplasia syndrome type 2, and risks of acute and chronic pancreatitis. Its FDA approval is currently limited to treatment for T2D and overweight or obese subjects.
Semaglutide's role in managing blood sugar and insulin levels and promoting weight loss is significant. It aids in lowering blood sugar levels by boosting insulin secretion and suppressing glucagon, thereby improving glycemic control. Additionally, its appetite-suppressing properties, likely due to hypothalamic stimulation and slowed gastric emptying, have proven effective in long-term weight management.
The therapeutic benefits of Semaglutide are vast and well-documented, particularly in treating type 2 diabetes and reducing cardiovascular risk. Furthermore, its effectiveness as a weight management tool in both diabetic and non-diabetic populations has been established through comprehensive clinical trials.
Emerging studies are revealing potential additional benefits of Semaglutide, such as in treating nonalcoholic steatohepatitis (NASH), kidney benefits in T2D patients, and possible neuroprotective effects in Parkinson's disease. The ongoing research and clinical developments promise to expand the understanding and application of this promising peptide.
Dosage Guidelines
For the treatment of Type 2 Diabeties, semaglutide is typically administered subcutaneously, following the dosage guidelines outlined under the Ozempic brand. The regimen begins with a starting dose of 0.25 mg once a week for the first four weeks. After this initial period, the weekly dose is increased to 0.50 mg.
Depending on the need for further glycemic control, the dosage may be escalated up to a maximum of 2 mg per week. Consistency in the timing of injections is key, with doses being administered on the same day each week. If a dose is missed, it should be taken within the following 5 days, with subsequent doses adhering to the original schedule.
When semaglutide is used for Chronic Weight Management, the dosing follows the recommendations specified for the Wegovy brand. The treatment starts with a dose of 0.25 mg once a week, maintained for the first four weeks. The dosage is then gradually increased over subsequent weeks: 0.50 mg weekly during weeks 5-8, 1 mg weekly during weeks 9-12, 1.7 mg weekly during weeks 13-16, and eventually reaching 2.4 mg weekly from week 17 onwards. Similar to the T2D treatment protocol, missed doses should be administered within 5 days of the scheduled date. If a patient is unable to tolerate a minimum weekly dose of 1.7 mg, discontinuing the treatment is recommended.
Starting Dose
.25 mg
Per Week
4 Weeks
Dose Increase - +.5mg /wk
.5-2.4 mg
Per Week
5-24 Weeks
Side Effects
Semaglutide, a widely used medication for type 2 diabetes and weight management, is generally well-tolerated but can cause a range of side effects. Most of these are mild and transient, particularly gastrointestinal issues that tend to subside as patients adjust to the medication. These side effects, observed with both oral and parenteral (injectable) forms of semaglutide, include:
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Constipation
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Diarrhea
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Indigestion
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Abdominal pain
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Nausea
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Vomiting
The severity and occurrence of these gastrointestinal disturbances can be time- and dose-dependent. While the exact mechanisms behind these effects are not fully understood, they are believed to be related to semaglutide's impact on intestinal nutrient absorption and gastric motility. Oral formulations of semaglutide are often associated with more pronounced gastrointestinal side effects, whereas the injectable form may lead to irritation at the injection site.
In addition to these common side effects, semaglutide can also cause serious adverse reactions, although these are rare. It's crucial for users to be aware of these potential risks and seek immediate medical attention if they occur:
Hypoglycemia: Semaglutide can lower blood glucose levels, which may lead to hypoglycemic events, especially when used in combination with other antidiabetic medications.
Pancreatic inflammation and cancer: There are concerns, albeit without definitive evidence, linking GLP-1 receptor agonists like semaglutide to pancreatitis and pancreatic cancer, particularly in patients with a history of pancreatitis.
Thyroid cancer: In animal studies, GLP-1 receptor agonists have been associated with thyroid C-cell hyperplasia and malignancies, making semaglutide contraindicated in individuals at risk of thyroid cancer.
Diabetic retinopathy: Rare cases of retinal complications, including blindness and vitreous hemorrhage, have been reported, often linked with concurrent insulin use.
Gallbladder disease: Semaglutide may increase the risk of gallbladder problems like cholelithiasis, with symptoms including jaundice and fever.
Kidney injury: The medication can cause renal impairment and dehydration, leading to severe gastrointestinal upset.
Hypersensitivity reactions: Rare but severe allergic reactions such as anaphylaxis, angioedema, rash, and urticaria have been reported.
Given these potential risks, it is important for healthcare providers and patients to carefully consider the safety of semaglutide, especially in individuals with a history or increased risk of renal failure, biliary disease, thyroid cancer, diabetic retinopathy, and pancreatitis. Additionally, combining semaglutide with other diabetic therapies requires close medical supervision to manage the risk of hyperglycemia.
Precautions and warnings regarding the use of semaglutide extend to specific populations:
Pregnancy and Lactation: The safety of semaglutide during pregnancy and lactation is not well established. Animal studies have raised concerns about potential fetal harm, but the benefits of managing diabetes during pregnancy might outweigh the risks. Decisions should be made individually with a healthcare provider.
Pediatric and Geriatric Use: The use of semaglutide in children under 12 is not approved, and there is limited safety data in the geriatric population.
This overview is not exhaustive, and those handling semaglutide should refer to the drug's prescribing information and follow medical guidance closely.
References:
Safety of Semaglutide
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.
Author: Mark M. Smits, Daniël H. Van Raalte
Publication Date: 07 July 2021
Clinical potential of treatment with semaglutide in type 2 diabetes patients
In these studies, semaglutide was found to provide significant and clinically relevant reductions in HbA1c, fasting plasma glucose (FPG), glucose excursions, body weight and blood pressure. The reduction in glycaemic parameters was more pronounced than that in the comparator GLP-1RAs. The rate of hypoglycemia is very low during treatment with semaglutide if not combined with sulphonylureas or insulin. A cardiovascular outcome trial (CVOT) was performed before the approval of semaglutide, at the request of legal authorities. Not only non-inferiority was confirmed, but also superiority compared with placebo used in a population of patients with type 2 diabetes and CVD treated with oral antihyperglycaemic drugs (OADs) and/ or insulin with regard to the primary composite endpoint: death from cardiovascular (CV) causes, nonfatal myocardial infarction or nonfatal stroke.
Authors: Michael E Røder
Published: 02 Dec 2019
Once-Weekly Semaglutide for Weight Management: A Clinical Review
Semaglutide 2.4 mg has consistently demonstrated clinically significant weight loss across all phase 3 STEP (semaglutide treatment effect in people with obesity) trials, and long-term efficacy and safety have been confirmed for up to 2 years.
Authors: Abby Fornes, PharmD, Jamie Huff, and Miranda Godfrey
Published: May 13, 2022
Wegovy (Semaglutide): A New Weight Loss Drug for Chronic Weight Management
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.Authors: L. Pickart, Jessica Michelle Vasquez-Soltero, A. Margolina
Published: May 25, 2023