Have you ever wondered about a more comprehensive approach that leverages the potential of medications like Semaglutide (OZEMPIC®/WEGOVY®)? If you’re eager to elevate your weight loss management strategies to the next level, you’re in the right place. Welcome to a journey that unveils the power of a comprehensive Semaglutide (OZEMPIC®/WEGOVY®) protocol for medical weight loss. In this protocol, we delve into the intricacies of this groundbreaking drug, equipping you with insights that could redefine your approach and amplify patient outcomes. If you’re ready to harness the potential of Semaglutide (OZEMPIC®/WEGOVY®) in the realm of weight management, this read is for you.
I. Introduction to Semaglutide as a Medical Weight Loss Treatment Option
Semaglutide is a glucagon-like peptide-1 receptor agonist initially FDA approved for the treatment of type 2 diabetes. In clinical trials, it has demonstrated significant weight loss effects, leading to its FDA approval for the following indication and usage:
WEGOVY® is a glucagon-like peptide-1 receptor agonist indicated as an adjunct to a reduced calorie diet and increased physical activity for chronic weight management in:
adult patients with an initial body mass index of
• 30 kg/m2 or greater or
• 27 kg/m2 or greater in the presence of at least one weight-related comorbid condition.
pediatric patients aged 12 years and older with an initial BMI at the 95th percentile or greater for age and sex.
The mechanism of action of semaglutide mimics the effects of the native hormone GLP-1, which is released in response to food intake. By binding to GLP-1 receptors in the brain, semaglutide reduces appetite and food intake. Additionally, semaglutide slows gastric emptying and improves insulin secretion, which improves glycemic control.
The efficacy of semaglutide as a weight loss treatment option has been demonstrated in several clinical trials, including the SUSTAIN (Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes) and PIONEER (Peptide Innovation for Early Diabetes Treatment) trials for type 2 diabetes, as well as the STEP (Semaglutide Treatment Effect in People with Obesity) trials, which specifically focused on weight loss. These trials showed weight reduction and improvement in glycemic control.
Understanding Glucagon & GLP-1
Glucagon and glucagon-like peptide-1 (GLP-1) are two peptide hormones that regulate glucose homeostasis.
Glucagon, a 29-amino-acid hormone, is secreted by the alpha cells of the pancreatic islets in response to low blood glucose levels. It raises blood glucose levels by stimulating glycogenolysis and gluconeogenesis in the liver. Also, glucagon promotes lipolysis in adipose tissue, providing free fatty acids as an alternative energy source during periods of low glucose availability. Since, insulin promotes glucose uptake and storage, glucagon is a counter-regulatory hormone.
GLP-1, a 30-amino-acid hormone, is secreted by the L-cells of the gastrointestinal tract in response to food intake. GLP-1 helps in glucose homeostasis by enhancing glucose-dependent insulin secretion from the pancreatic beta cells, inhibiting glucagon secretion, and delaying gastric emptying. These actions result in reduced postprandial glycemia and improved overall glycemic control. GLP-1 also has central effects on the regulation of appetite and body weight, as it acts on the hypothalamus to promote satiety and reduce food intake.
FDA approval and indications
Semaglutide has the FDA approval for two indications: type 2 diabetes and chronic weight management in adults with obesity or overweight.
1. Type 2 Diabetes:
Semaglutide (Ozempic) was first approved by the FDA in December 2017 as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. It is a once-weekly subcutaneous injection at doses of 0.5 mg or 1.0 mg.
2. Chronic Weight Management:
In June 2021, the FDA approved semaglutide (Wegovy) at a higher dose of 2.4 mg for chronic weight management in adults with obesity or overweight with at least one weight-related comorbidity, such as type 2 diabetes, hypertension, or dyslipidemia.
II. Understanding Semaglutide
Mechanism of action
Semaglutide is a glucagon-like peptide-1 receptor agonist that mimics the effects of GLP-1, a hormone that regulates glucose homeostasis, appetite, and energy balance. Semaglutide has a 94% amino acid sequence homology with endogenous GLP-1. It has an extended half-life (1 week) due to its structural modifications, allowing for once-weekly subcutaneous administration.
The mechanism of action of semaglutide includes the following:
1. Enhanced glucose-dependent insulin secretion: Glucose dependent stimulated insulin release from pancreatic β-cells, which improves glycemic control.
2. Suppress glucagon secretion: Inhibits glucagon release from pancreatic α-cells, which reduces hepatic glucose production, which improves glycemic control.
3. Delay gastric emptying: Slows gastric emptying, which helps in reduce postprandial glucose excursions (the change in glucose concentration from before to after a meal) and promote satiety.
4. Reduce appetite and caloric intake: Acts on the central nervous system to regulate appetite.
Clinical trial outcomes and safety profile
SUSTAIN, PIONEER and STEP are the three major clinical trials for the efficacy of semaglutide in type 2 diabetes and weight loss.
The SUSTAIN (Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes) trials were a series of global, randomized, controlled clinical trials that investigated the efficacy and safety of semaglutide in patients with type 2 diabetes. The trial included 3,297 patients with type 2 diabetes and a high cardiovascular risk, who were randomized to receive either semaglutide (0.5 mg or 1.0 mg) subcutaneously once weekly or placebo. SUSTAIN-6 demonstrated a significant reduction in HbA1c levels and body weight compared to placebo, along with a reduction in cardiovascular risk.
Results:
– The primary outcome (composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) occurred in 6.6% of patients in the semaglutide group and 8.9% in the placebo group, indicating a 26% lower risk with semaglutide.
– Semaglutide led to a significant reduction in HbA1c levels compared to placebo- Patients receiving semaglutide experienced significant weight loss compared to those on placebo
PIONEER Trials (Peptide Innovation for Early Diabetes Treatment):
The PIONEER (Peptide Innovation for Early Diabetes Treatment) trials were a series of global, randomized, controlled clinical trials that investigated the efficacy, safety, and tolerability of oral semaglutide, a GLP-1 receptor agonist, in patients with type 2 diabetes.
The trial included 3,183 patients with type 2 diabetes and established cardiovascular disease, chronic kidney disease, or both, who were randomized to receive either oral semaglutide (14 mg) once daily or placebo. PIONEER-6 showed that oral semaglutide significantly reduced HbA1c levels and body weight and was non-inferior to placebo in terms of safety.
Results:
– Oral semaglutide reduced HbA1c levels compared to placebo
– Oral semaglutide patients experienced significant weight loss compared to those on placebo
– The primary outcome (composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) occurred in 3.8% of patients in the oral semaglutide group and 4.8% in the placebo group, which showed that cardiovascular safety of oral semaglutide was non-inferior to placebo.
STEP Trials (Semaglutide Treatment Effect in People with Obesity):
STEP trials evaluated semaglutide for weight management in individuals with obesity.
The STEP (Semaglutide Treatment Effect in People with Obesity) trials were a series of global, randomized, controlled clinical trials that It investigated the efficacy and safety of subcutaneous semaglutide in individuals with obesity or overweight without diabetes.
A total of 1,961 adult participants with a BMI of at least 30 or at least 27 with at least one weight-related comorbidity were randomized to receive either semaglutide (2.4 mg) or placebo, administered subcutaneously once weekly, along with lifestyle intervention.
STEP-1 demonstrated that semaglutide led to a significant reduction in body weight compared to placebo, with a mean weight loss of 14.9% in the semaglutide group.
Results:
– The primary endpoint was the change in body weight from baseline to week 68. The patients in the semaglutide group experienced a mean weight loss of 14.9% compared to 2.4% in the placebo group.
– Participants in the semaglutide group achieved a weight loss of at least 5%, 10%, or 15%, and improvements in secondary endpoints, such as waist circumference, blood pressure, and lipid levels, compared to the placebo group.
CONTRAINDICATIONS
According to the package insert, Wegovy® is contraindicated in patients with the following:
- personal or family history of Medullary Thyroid Carcinoma
- patients with Multiple Endocrine Neoplasm type 2
- patients with a prior serious hypersensitivity reaction to semaglutide or to any of the excipients in Wegovy®. Serious hypersensitivity reactions, including anaphylaxis and angioedema have been reported with Wegovy®
LIMITATIONS OF USE
According to the package insert, Wegovy®
- should not be coadministered with other semaglutide-containing products or with any GLP-1 receptor agonist
- safety and efficacy in combination with other products intended for weight loss, including prescription drugs, over-the-counter drugs, and herbal preparations, have not been established
- has not been studied in patient with a history of pancreatitis
WARNINGS AND PRECAUTIONS
The safety profile of semaglutide in the treatment of obesity has been investigated through several clinical trials. Here are the top warnings based on its clinical trial:
Risk of Thyroid C-Cell Tumors: Patient’s initial work up and maintanence physical exam should include the thyroid exam and neck imaging. Serum calcitonin should also be measured.
Acute Pancreatitis: In clinical trials, acute pancreatitis was observed in patients treated with Wegovy®. Patients should be monitored for signs and symptoms of acute pancreatitis. Semaglutide should be discontinues and not restarted if this complication should arise.
Acute Gallbladder Disease: Rapid weight loss increases the risk of acute gallbladder disease. However, the incidence of gallbladder disease, even after factoring for the degree of weight loss, was greater in semaglutide patients than in placebo. In clinical trials in adult patients, cholelithiasis was reported by 1.6% of Wegovy® patients and 0.7% of placebo patients. Cholecystitis was reported by 0.6% of Wegovy® patients and 0.2% of placebo patients. In a clinical trial in pediatric patients aged 12 years and older, cholelithiasis was reported by 3.8% of Wegovy® patients and 0% placebo patients. Cholecystitis was reported by 0.8% of Wegovy® pediatric patients and 0% placebo patients. Patients should be monitored for signs and symptoms of acute gallbladder disease.
Hypoglycemia: Semaglutide lowers blood glucose and can cause hypoglycemia. In clinical trials, hypoglycemia was reported in 6.2% of Wegovy® patients versus 2.5% of placebo patients. There is an increased risk of hypoglycemia in patients who take semaglutide with other hypoglycemic medication, such as sulfonylurea or insulin. Patients should be warned of the risk of hypoglycemia and blood glucose should be monitored in diabetic patients.
Acute Kidney Injury: Patients have experienced acute kidney injury or worsening renal failure requiring dialysis. Renal function should be monitored when initiating or escalating doses of semaglutide. Majority of the acute kidney injury events occured due to patient experiencing adverse reactions like nausea, vomiting, diarrhea or abdominal pain, which lead to volume depletion.
Hypersensitivity Reactions: Anaphylaxis or angioedema has been reported in clinical trials. Patients with a history of hypersensitivity reaction to other GLP-1 receptor agonist should not be started on semaglutide.
Diabetic Retinopathy Complications in Patients with Type 2 Diabetes: Temporary worsening of diabetic retinopathy has been associated with rapid improvement in glucose control. In clinical trials, diabetic retinopathy was reported by 4.0% of Wegovy® patients and 2.7% of placebo patients. Patients with a history of diabetic retinopathy should be closely monitored.
Heart Rate Increase: Both adults and pediatric patients experienced mean increases in resting heart rate of 1 to 4 beats per minute (bpm) in semaglutide patients compared to placebo in clinical trials. Heart rate should be monitored at every check up. Patients should instructed to report palpitations or feelings of a racing heartbeat while at rest. Semaglutide should be stopped if a patient experiences sustained increasd heart rate.
Suicidal Behavior and Ideation: Clinical studies shows a similar rate of psychiatric disorders in both semaglutide and placebo groups. However, patient with history of suicidal thoughts were excluded from the clinical trial. Other weight loss medications have been linked to suicidal behavior and ideations. Therefore, it is advisable to monitor patients for mood and behavior disorders. Semaglutide should be avoided in patients with history of depression or suicide. Semaglutide should be stopped in any patients with suicidal thoughts.
ADVERSE EVENTS
According to clinical studies, gastrointestinal adverse events are the most common and tend to be mild to moderate, decreasing over time.
Common gastrointestinal AEs include:
- Nausea: The most frequently reported adverse event, with an incidence of 44% in the semaglutide group compared to 18% in the placebo group during the STEP-1 trial.
- Diarrhea: Occured in 28.3% of patients on semaglutide in the STEP-1 trial, compared to 12.4% in the placebo group.
- Vomiting: Occured in 22% of patients on semaglutide in the STEP-1 trial, compared to 7.5% in the placebo group.
- Constipation: Occurred in 18.8% of patients on semaglutide in the STEP-1 trial, compared to 6.8% in the placebo group.
Other adverse events with an incidence ≥5% are as follows:
abdominal pain, headache, fatigue, dyspepsia, dizziness, abdominal distention, eructation, hypoglycemia in patients with type 2 diabetes, flatulence, gastroenteritis, gastroesophageal reflux disease, and nasopharyngitis.
In conclusion, the safety profile of semaglutide in obesity treatment is generally favorable, but post marketing surveillance will give physicians and patients a greater clarity.
III. Patient Selection and Assessment
Criteria for patient eligibility, medical history and contraindications
According to the package insert:
Wegovy® (semaglutide) injection 2.4 mg is indicated as an adjunct to a reduced calorie diet and increased physical activity for chronic weight management:
YES:
- adults with an initial body mass index (BMI) of ≥30 kg/m2 (obesity) or ≥27 kg/m2 (overweight) in the presence of at least one weight-related comorbid condition (e.g., hypertension, type 2 diabetes mellitus, or dyslipidemia)
- pediatric patients aged 12 years and older with an initial BMI at the 95th percentile or greater standardized for age and sex (obesity)
NO:
- Patients with a personal or family history of MTC
- Patients with MEN 2
- Patients with a prior serious hypersensitivity reaction to semaglutide or to any of the excipients in semaglutide
WARNING & PRECAUTIONS:
Risk of the following:
- Thyroid C-Cell Tumors
- Acute Pancreatitis
- Acute Gallbladder Disease
- Hypoglycemia
- Acute Kidney Injury
- Hypersensitivity Reactions
- Diabetic Retinopathy Complications in Patients with Type 2 Diabetes
- Heart Rate Increase
- Suicidal Behavior and Ideation
ADDITIONAL
Patients should be warned about the following:
- History of type 1 diabetes or diabetic ketoacidosis, as semaglutide is not indicated for these conditions.
- History of gastrointestinal disorders (e.g., gastroparesis or inflammatory bowel disease), as semaglutide may slow gastric emptying and worsen these diseases.
- Potential drug interactions, especially those that have a narrow therapeutic index or require close monitoring, such as oral anticoagulants, antiplatelet agents, antihypertensive medications, and other antidiabetic medications (1,3).
- Pregnancy and breastfeeding: Semaglutide is classified as pregnancy category C. Semaglutide should be discontinued at least 2 months before a planned pregnancy. It is unknown whether semaglutide is excreted in human milk.
Baseline measurements and laboratory tests
Before initiating semaglutide treatment, the following baseline measurements and laboratory tests should be considered:
1. BMI and Vital Signs
Body weight and body mass index (BMI), blood pressure and heart rate (1, 3).
2. Laboratory tests:
Glucose
Lipid profile
Renal Function
Liver Function
Thyroid Function
(1, 4, 5).
IV. Semaglutide Protocol Implementation
Starting dose and titration schedule
WEGOVY® is a prefilled singe dose pen that delivers doses of 0.25mg, 0.5 mg, 1 mg, 1.7 mg or 2.4 mg.
OZEMPIC® is a prefilled multidose, single patient use pen that delivers the following:
2 mg/3 mL (0.68 mg/mL) Single-patient-use pen that delivers 0.25 mg or 0.5 mg per injection
2 mg/1.5 mL (1.34 mg/mL) Single-patient-use pen that delivers 0.25 mg or 0.5 mg per injection
4 mg/3 mL (1.34 mg/mL) Single-patient-use pen that delivers 1 mg per injection
8 mg/3 mL (2.68 mg/mL) Single-patient-use pen that delivers 2 mg per injection
The semaglutide starting dose and titration schedule are important to minimize side effects and ensure optimal therapeutic efficacy. The recommended semaglutide dosing schedule, as per the prescribing information and clinical trials, is as follows:
Administer WEGOVY® once weekly, on the same day each week, at any time of day, with or without meals
Inject subcutaneously in the abdomen, thigh or upper arm (alternate injection site)
In 4 week intervals, increase the dose until a dose of 2.4 mg is reached. For example:
Week 1 – 4: Initiate at 0.25 mg once weekly for 4 weeks.
Week 5 – 8: Initiate at 0.5 mg once weekly for 4 weeks.
Week 9 – 12: Initiate at 1 mg once weekly for 4 weeks.
Week 13 – 16: Initiate at 1.7 mg once weekly for 4 weeks.
Week 17 – 20: Initiate at 2.4 mg once weekly for 4 weeks.
The maintenance dose of WEGOVY® is 2.4 mg once weekly
OZEMPIC® does NOT have a 1.7mg or 2.4mg dosing prefilled pen.
Dose escalation should be dependent of patient side effect profile and gastrointestinal tolerability. If the patient does not tolerate a dose, then consider stoping or delaying the dose escalation for 4 weeks.
If a dose is missed, then it should be administered as soon as possible within 2 days of the missed dose. If more than 2 days have passed, then the patient should skip the missed dose and administer the next dose on the regularly scheduled day. Patients should not administer two doses within the same week.
If a patient discontinues semaglutide for more than two weeks, then it is recommended to re-initiate treatment at the 0.25 mg once-weekly dose and follow the original titration schedule.
If the patient cannot tolerate the 2.4mg dose, then decrease the dose to 1.7mg for 4 weeks. After 4 weeks, increase the dose to the maintenance dose of 2.4mg. If the patient cannot tolerate the 2.4mg dose, then discontinue semaglutide.
Monitoring patient progress and side effects
The American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE) guidelines recommend that patients receiving treatments for obesity be evaluated every 4-12 weeks. During the first few months of the treatment when dosing titration occurs, it is essential to maintain close monitoring for side effects. Once the patient has reached the maintanence dose, follow up appointments can be scheduled according to the needs of the patient and the physician’s discretion. More frequent follow ups may be required if the patient is experiencing side effects.
Adjusting the treatment plan as needed
Dose escalation should be dependent of patient side effect profile and gastrointestinal tolerability. If the patient does not tolerate a dose, then consider stoping or delaying the dose escalation for 4 weeks.
If a dose is missed, then it should be administered as soon as possible within 2 days of the missed dose. If more than 2 days have passed, then the patient should skip the missed dose and administer the next dose on the regularly scheduled day. Patients should not administer two doses within the same week.
If a patient discontinues semaglutide for more than two weeks, then it is recommended to re-initiate treatment at the 0.25 mg once-weekly dose and follow the original titration schedule.
If the patient cannot tolerate the 2.4mg dose, then decrease the dose to 1.7mg for 4 weeks. After 4 weeks, increase the dose to the maintenance dose of 2.4mg. If the patient cannot tolerate the 2.4mg dose, then discontinue semaglutide.
Potential drug interactions and considerations
Based on research studies, the following drug interactions and considerations should be taken into account when using semaglutide:
Oral medication: Semaglutide slows gastric emptying, which can affect the absorption of other oral medications. It is essential to monitor the efficacy of other oral medication and adjust dosages as needed.
Insulin and sulfonylureas: Semaglutide increases the risk of hypoglycemia when used with other medication used to control hyperglycemia. Semaglutide use in patients using insulin has not been evaluated.
Warfarin and other anticoagulants: Semaglutide increases the risk of bleeding when used with anticoagulants.
Alcohol: Semaglutide mixed with alcohol may potentially affect the liver or cause hypoglycemia.
Use in Pregnancy
Semaglutide has not been testing in pregnant women. Discontinue semaglutide when the patient is pregnant. Also, semaglutide should be stopped at least 2 months before planning for pregnancy.
HOW TO INCORPORATE SEMAGLUTIDE INTO YOUR MEDICAL WEIGHT LOSS PRACTICE?
For detailed discussion about how to start your own medical weight loss practice, please go to our Medical Weight Loss Training course.
There you will find resources about compounding semaglutide, pricing and other prescription options. You will also discover a complete A to Z package including the following:
- Management of Obesity
- Diets
- Medical Managed Plans
- Medication
- Alternative Treatments
- Medical Weight Loss Protocol Options
- Business Models
- Start Up and Marketing
Upon course registration, you’ll receive an invaluable start-up kit including consent forms, treatment records, measurement chart, consultation outline, questionnaire, sample diet, exercise plan, behavior modification recommendations, vendor list, references, and articles on different diets, drugs, and obesity.
BONUS
Medical Weight Loss Certification Training Manual
Tirzepatide Protocol as Weight Loss Treatment
For more information, contact us at email@MedicalWeightLossTraining.com or call us at (212) 470-8059 TODAY!
