Semaglutide has emerged as a prominent treatment in both weight management and glycemic control, especially beneficial for patients grappling with obesity or type 2 diabetes. Whether initiating semaglutide, contemplating microdosing, or strategizing a long-term regimen, a firm grasp of dosing strategies is paramount to amplifying its benefits while mitigating potential side effects. At Mountcastle Medical Spa & Laser Center, personalized care is available for patients exploring weight management and glycemic control with semaglutide.
Understanding Semaglutide
Semaglutide belongs to a class of drugs known as GLP-1 receptor agonists. It functions by mimicking the action of the body’s natural glucagon-like peptide-1 hormone. This mechanism promotes satiety, leading to a reduction in food intake. The bioavailability of semaglutide is 89% when injected subcutaneously.
How Semaglutide Works
Semaglutide promotes satiety, which leads to a reduction in food intake.
Administration and Bioavailability
Semaglutide is administered subcutaneously without regard to meals. The bioavailability of semaglutide is 89% when injected subcutaneously. Administration sites include the abdomen, thigh, and upper arm. When injected once weekly, semaglutide protects from natural degradation by dipeptidyl-peptidase 4 (DPP-4).
Elimination
Semaglutide will be present for approximately 5-7 weeks after the last dose and is eliminated via the urine and feces.
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Standard Dosing Regimen
The standard dosing regimen for semaglutide involves a gradual titration to help the body adjust and minimize potential side effects such as nausea or gastrointestinal discomfort. Typically, the dose is escalated every 4 weeks to doses of 0.5 mg, 1 mg, and 1.7 mg, and the maintenance dose of 2.4 mg.
Microdosing Semaglutide
Microdosing refers to starting semaglutide at smaller-than-standard doses and increasing gradually over a longer time frame.
Maintenance Dosing
Once therapeutic goals are achieved, it’s crucial to maintain results with a sustainable, long-term dosing plan. Some patients may opt to taper their dose after achieving goals.
Semaglutide and Weight Management: Clinical Trial Data
Clinical trials have demonstrated the efficacy of semaglutide 2.4 mg in promoting significant weight loss compared with either placebo or liraglutide. Details of these trials are shown in Table 1. The search terms used for these trials included: semaglutide 2.4, weight, and obesity, with information sourced from clinicaltrials.gov.
STEP Trials
The STEP (Semaglutide Treatment Effect in People with obesity) trials provide comprehensive data on the effectiveness of semaglutide for weight management.
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STEP 1: In STEP 1, lifestyle interventions were consistent with increased physical activity. These included 30 individual visits with a registered dietitian and moderate-intensity exercise spread over 3 to 5 sessions per week. Results showed that 86.4% of patients treated with semaglutide 2.4 mg vs. placebo achieved a weight loss of 5% or more at 68 weeks. Specifically, there was a -14.9% weight change with semaglutide 2.4 mg vs. placebo.
STEP 2: This trial involved patients with at least one weight-related comorbidity and did not have diabetes. The lifestyle interventions were consistent with STEP 1, including increased physical activity.
STEP 3: SQ semaglutide 2.4 mg vs. placebo resulted in -16.0% weight change with semaglutide vs. placebo at 68 weeks. 86.6% of patients treated with semaglutide vs. placebo achieved a weight loss of 5% or more.
STEP 4: This trial examined weight loss after discontinuation of semaglutide. All patients received a total of 20 weeks of semaglutide therapy. Following this, patients were randomized to either continue semaglutide therapy or replace therapy with placebo. The lifestyle interventions as described in STEP 1 were provided to both groups. Results showed -17.4% weight change with continued semaglutide vs. -16.0% with semaglutide vs. placebo at week 68.
STEP 5: This 68-week trial evaluated -15.2% weight change with semaglutide vs. placebo. 77.1% of patients treated with semaglutide vs. placebo achieved a weight loss of 5% or more.
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Other Notable Findings
- Dose-Dependent Weight Loss: Studies indicated that 60-91% of patients had a weight loss of 5% or more depending on dose vs. placebo. For example, -13.8% with 0.4 mg vs. 0.05 mg.
- Liraglutide Comparison: In one trial, -15.8% weight change with semaglutide vs. liraglutide (exploratory endpoint) was observed. 87.2% of patients treated with semaglutide vs. liraglutide achieved a weight loss of 5% or more.
- SELECT Trial: The SELECT trial data for up to 2 years confirmed the efficacy and safety of semaglutide.
Considerations Before Starting Semaglutide
Before starting semaglutide, it is important to discuss several factors with your healthcare provider. Semaglutide is indicated for weight management in overweight or obese adults, and it should be used with lifestyle changes. Semaglutide is not suitable for everyone.
Medical History
Inform your healthcare provider if you:
- Have a lump or swelling in your neck, hoarseness, trouble swallowing, or shortness of breath, as these may be symptoms of thyroid cancer. In studies with rodents, Wegovy® and medicines that work like Wegovy® caused thyroid tumors, including thyroid cancer. It is not known whether semaglutide causes thyroid C-cell tumors, including MTC.
- Are pregnant or plan to become pregnant, as Wegovy® may harm your unborn baby. Do not use this medicine for at least 2 months before you plan to become pregnant. Counseling on contraception and pregnancy may be needed because of the problems that can occur during pregnancy in patients with diabetes.
- Are breastfeeding or plan to breastfeed.
Current Medications
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Do not take other medicines during the time you are using semaglutide unless they have been discussed with your doctor. This especially includes nonprescription medicines such as aspirin, and medicines for appetite control, asthma, colds, cough, hay fever, or sinus problems. Wegovy® may affect the way some medicines work, and some medicines may affect the way Wegovy® works. It is important to consider potential drug interactions and whether semaglutide may inhibit drug transporters.
If you are taking other medicines to treat diabetes, including sulfonylureas or insulin, be aware of the increased risk of low blood sugar (hypoglycemia). Talk to your healthcare provider about how to recognize and treat low blood sugar, and check your blood sugar before you start and while you take Wegovy®.
Other Health Conditions
Inform your healthcare provider if you have or have had:
- Inflammation of your pancreas (pancreatitis). Stop using Wegovy® and call your healthcare provider right away if you have severe pain in your stomach area (abdomen) that will not go away, with or without nausea or vomiting.
- Gallbladder problems. Wegovy® may cause gallbladder problems, including gallstones. Some gallstones may need surgery. Check with your doctor right away if you have gaseous stomach pain, indigestion, recurrent fever, severe nausea or vomiting, stomach fullness, or yellow eyes or skin. These may be symptoms of gallbladder problems (eg, cholelithiasis, cholecystitis).
- Diabetic retinopathy. This medicine may cause diabetic retinopathy. Check with your doctor if you have blurred vision or any other changes in vision.
Important Precautions and Potential Side Effects
During semaglutide treatment, it is crucial to adhere to specific precautions and monitor for potential side effects.
Regular Check-ups
It is very important that your doctor check your progress at regular visits to make sure that this medicine is working properly. Blood and urine tests may be needed to check for unwanted effects.
Lifestyle Considerations
- Alcohol: Drinking alcohol may cause severe low blood sugar. Discuss this with your health care team.
- Counseling: Other family members need to learn how to prevent side effects or help with side effects if they occur. Also, diabetic patients may need special counseling about diabetes medicine dosing changes that might occur because of lifestyle changes, such as changes in exercise and diet.
- Travel: Keep a recent prescription and your medical history with you. Be prepared for an emergency as you would normally. Make allowances for changing time zones and keep your meal times as close as possible to your usual meal times.
Emergency Preparedness
In case of emergency, there may be a time when you need emergency help for a problem caused by your diabetes. You need to be prepared for these emergencies. It is a good idea to wear a medical identification (ID) bracelet or neck chain at all times. Also, carry an ID card in your wallet or purse that says that you have diabetes and a list of all of your medicines.
Serious Side Effects and What to Do
- Thyroid Tumors: This medicine may increase the risk of having thyroid tumors. Tell your doctor right away if you have a lump or swelling in your neck or throat, trouble swallowing or breathing, or if your voice gets hoarse.
- Pancreatitis: Pancreatitis (swelling of the pancreas) may occur while you are using this medicine. Check with your doctor right away if you have sudden and severe stomach pain, chills, constipation, nausea, vomiting, fever, or lightheadedness.
- Hypoglycemia: This medicine does not cause hypoglycemia (low blood sugar). However, low blood sugar can occur when you use semaglutide with other medicines, including insulin or sulfonylureas, that can lower blood sugar. Low blood sugar also can occur if you delay or miss a meal or snack, exercise more than usual, drink alcohol, or cannot eat because of nausea or vomiting.
- Symptoms of Low Blood Sugar: anxiety, behavior change similar to being drunk, blurred vision, cold sweats, confusion, cool, pale skin, difficulty with thinking, drowsiness, excessive hunger, fast heartbeat, headache (continuing), nausea, nervousness, nightmares, restless sleep, shakiness, slurred speech, or unusual tiredness or weakness.
- Treatment for Low Blood Sugar: If symptoms of low blood sugar occur, eat glucose tablets or gel, corn syrup, honey, or sugar cubes, or drink fruit juice, non-diet soft drink, or sugar dissolved in water to relieve the symptoms. Also, check your blood for low blood sugar. Glucagon is used in emergency situations when severe symptoms including seizures or unconsciousness occur. Have a glucagon kit available, along with a syringe and needle, and know how to use it. Members of your family should also know how to use it.
- Allergic Reactions: This medicine may cause serious allergic reactions, including anaphylaxis and angioedema, which can be life-threatening and require immediate medical attention. Check with your doctor right away if you have a rash, itching, hoarseness, trouble breathing, trouble swallowing, or any swelling of your hands, face, mouth, or throat while you are using this medicine.
- Kidney Problems and Dehydration: Check with your doctor right away if you have bloody urine, decreased amount of urine, increased blood pressure, increased thirst, loss of appetite, lower back or side pain, nausea, swelling of the face, fingers, or lower legs, trouble breathing, weight gain, or vomiting. These may be symptoms of dehydration which can lead to serious kidney problem. It is important for you to drink fluids to help reduce your chance of dehydration. Diarrhea, nausea, and vomiting may cause a loss of fluids (dehydration), which may cause kidney problems.
- Severe Stomach Problems: This medicine may cause severe stomach or bowel problems. Check with your doctor right away if you have belching, bloated or full feeling, blood in stools, constipation, diarrhea, excess air or gas in the stomach, hiccups, nausea, stomach pain, uncomfortable swelling around the anus, or vomiting.
- Increased Heart Rate: Wegovy® can increase your heart rate while you are at rest. Check with your doctor right away if you have fast or pounding heart beat.
- Hyperglycemia: Hyperglycemia (high blood sugar) may occur if you do not take enough or skip a dose of your antidiabetic medicine, overeat or do not follow your meal plan, have a fever or infection, or do not exercise as much as usual.
- Symptoms of High Blood Sugar: blurred vision, drowsiness, dry mouth, flushed, dry skin, fruit-like breath odor, increased urination (frequency and amount), ketones in the urine, loss of appetite, stomachache, nausea or vomiting, tiredness, trouble breathing (rapid and deep), unconsciousness, or unusual thirst.
- Action for High Blood Sugar: If symptoms of high blood sugar occur, check your blood sugar level and then call your doctor for instructions.
- Mental Health Changes: This medicine may cause some people to be agitated, irritable, or display other abnormal behaviors. It may also cause some people to have suicidal thoughts and tendencies or to become more depressed. Also tell your doctor if you have sudden or strong feelings, including feeling nervous, angry, restless, violent, or scared. You should pay attention to any mental changes, especially sudden changes in your mood, behaviors, thoughts, or feelings. If you or your caregiver notice any of these side effects, tell your doctor right away.
- Food or Liquid Aspiration: Wegovy® may increase the chance of food getting into your lungs during surgery or other procedures that use anesthesia or deep sleepiness (deep sedation).
Other Approved Medications for Chronic Weight Management
It's important to note that semaglutide is one of several approved medications for chronic weight management. These include:
- Liraglutide 3.0 mg: Another GLP-1 receptor agonist.
- Bupropion ER/Naltrexone ER: A combination medication.
The choice of medication should be based upon the side effects, precautions, and contraindications of a medication, as well as individual patient factors.
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