Semaglutide and Tirzepatide FAQ’s
Semaglutide and Tirzepatide FAQ’s
Anti-obesity medications like Semaglutide (Wegovy) and Tirzepatide (Zepbound) have shown significant results for weight loss, with results ranging from 14.9% to 17.4% total body weight loss from baseline in the STEP trials for Semaglutide, and 25.3% total body weight loss from baseline for Tirzepatide in the SURMOUNT-4 trial.
Who meets criteria for anti-obesity medication treatment?
These medications are indicated in patients who have failed comprehensive and lifestyle modifications with a BMI of ≥ 27-29.9 plus one or more weight-related conditions (such as type 2 diabetes, high cholesterol, high blood pressure, heart disease, obstructive sleep apnea, symptomatic osteoarthritis, hepatic steatosis, and difficulty with physical function) or a BMI ≥ 30 (with or without additional co-morbidities). Abdominal obesity with a waist circumference of ≥ 40 inches in men and ≥ 35 inches in women is also an indication for treatment.
What distinguishes Wegovy from Ozempic, and Zepbound from Mounjaro?
Wegovy and Ozempic both have the same active ingredient of semaglutide. The brand names Wegovy and Ozempic refer to how the medications have been FDA approved for use for either weight loss or diabetes management, and they have different dosing recommendations and criteria for use. Specifically, Wegovy is FDA approved for treatment of obesity, and Ozempic is FDA approved for treatment of type 2 diabetes.
Similarly, Zepbound and Mounjaro both have the same active ingredient of tirzepatide. Zepbound is FDA approved for treatment of obesity and Mounjaro is FDA approved for treatment of type 2 diabetes.
How do they work?
Semaglutide is a glucagon-like peptide 1 receptor agonist (GLP-1 RA). Glucagon-like peptide 1 (GLP-1) is produced in our small intestine and colon, and is secreted naturally when we eat. It tells our stomach to slow down the rate at which food leaves the stomach and enters the small intestine to be digested, thus leading to a prolonged sense of fullness. GLP-1 also acts on receptors in the brain to decrease feelings of hunger, which leads to decreased food intake. Importantly, GLP-1 also plays a strong role in improving blood sugar levels. Since semaglutide is a GLP-1 receptor agonist, this medication mimics the natural release of the hormone leading to an increased effect.
Tirzepatide is a glucagon-like peptide 1 receptor agonist (GLP-1 RA) as well as a glucose-dependent insulinotropic polypeptide (GIP) receptor agonist. In addition to the mechanism of action of semaglutide, the GIP component adds an additional element of improved blood sugar control and further slowing of gastric emptying, leading to further decreased feelings of hunger.
What are the contraindications to use?
Prior hypersensitivity reaction to GLP-1 agonists
Personal or family history of medullary thyroid carcinoma. The manufacture’s label has a warning that there is an increased risk of medullary thyroid carcinoma in rodents treated with semaglutide and tirzepatide. This has only been shown in rat studies and the risk to humans is unknown. A systematic review and meta-analysis from 37 studies with almost 47,000 patients done in 2023 found that there was no increased risk of any cancer, including thyroid, with semaglutide. Of note, the CDC recognizes 13 cancers that are increased in the setting of having excess weight (BMI ≥ 25), with thyroid cancer being one.
Patients with Multiple Endocrine Neoplasia Type 2, a rare genetic disorder that can cause tumors and other medical issues.
Pregnancy
What are some adverse reactions of the medications?
Gastrointestinal symptoms, including abdominal pain, nausea, vomiting, constipation, and diarrhea are the most common adverse reactions. These typically occurred during initiation of treatment and during dose escalation. Due to side effects of delayed gastric emptying and the risk of food regurgitation or aspiration during anesthesia, patients undergoing elective surgery should hold semaglutide or tirzepatide for seven days prior to surgery.
Acute pancreatitis, chronic pancreatitis, and pancreatic adenocarcinoma have been reported with GLP-1 RAs like semaglutide and tirzepatide, but causality has not been firmly established. Obesity is a risk factor by itself for acute pancreatitis, along with elevated triglycerides, gallstones, and alcohol use. The SUSTAIN-6 trial found that semaglutide was associated with acute pancreatitis at similar rates to placebo controls.
Acute kidney injury. Reports of an increased creatinine level, which is a marker for kidney function have been associated with semaglutide and tirzepatide. It is recommended to monitor kidney function when initiating or escalating doses in patients reporting severe adverse gastrointestinal reactions or those with chronic kidney disease reporting severe adverse gastrointestinal reactions. The mechanism of possible acute kidney injury is felt to be related to dehydration secondary to severe vomiting and diarrhea. In a post-hoc analysis of multiple clinical trials, there was no difference in the incidence of acute kidney failure between semaglutide and placebo.
Gallbladder disease. Gallstone formation and cholecystitis (inflammation of the gallbladder typically associated with an impacted gallstone and infection) have been reported with semaglutide and tirzepatide. Risk factors include substantial or rapid weight loss. In general, rapid weight loss of 15 pounds or more per month from any cause has been associated with an increased risk of gallstone formation.
Diabetic retinopathy. An increased incidence of diabetic retinopathy complications was noted during the SUSTAIN-6 study, a clinical trial evaluating the impact of subcutaneous semaglutide on cardiovascular outcomes in patients with type 2 diabetes; complications included vitreous hemorrhage, onset of diabetes-related blindness, and the need for treatment with an intravitreal agent or retinal photocoagulation. In a separate analysis of clinical trial data, the effect was reported to be mainly observed in patients with preexisting diabetic retinopathy, and primarily attributable to the magnitude and rapidity of reduction in blood sugars during the first 16 weeks of the trial. Of note, worsening of preexisting diabetic retinopathy is a known consequence of rapid improvement of elevated blood sugars, especially in patients with poorly controlled diabetes. Further studies are underway to evaluate this association. At least one study from a large population database showed very few cases of diabetic retinopathy.
What happens if you stop taking Semaglutide or Tirzepatide?
Obesity is a chronic disease, and therefore should be managed as a chronic disease. Similar to other chronic diseases being exacerbated once stopping treatment (such as high blood pressure or high cholesterol), studies have shown that patients regain significant weight once they stopped these anti-obesity medications.
In the STEP 1 trial extension, one year after withdrawal of once-weekly subcutaneous semaglutide 2.4 mg and lifestyle intervention, participants regained two-thirds of their prior weight loss.
In the SURMOUNT-4 trial, participants who completed a 36-week period on tirzepatide experienced a mean weight reduction of 20.9%. At week 36, patients were randomized to either switch to a placebo or continue tirzepatide. The study found that those who continued tirzepatide experienced an additional 5.5% weight reduction during the following 52 week period, while those switched to placebo experienced a 14% weight regain.
What are some additional benefits from taking Semaglutide and Tirzepatide?
Semaglutide has been shown to reduce major cardiovascular events in adults with established cardiovascular disease who did not have diabetes as well as those with type 2 diabetes. It may also improve heart failure symptoms in individuals with heart failure with preserved ejection fraction, with a randomized trial demonstrating greater improvements in heart failure symptoms and exercise function.
Treatment with semaglutide has also been associated with lower total cholesterol and LDL cholesterol along with decreased blood pressure.
Treatment with tirzepatide has been associated with significantly lower all-cause mortality and major adverse cardiovascular events, improved cardiometabolic risk factors like cholesterol and blood pressure and improved heart failure symptoms, among others.
Florida Direct Primary Care
At Florida DPC, we offer Medical Weight Loss and Maintenance programs that are tailored to your specific needs, including body composition testing, vital signs monitoring, personalized nutrition guidance, and exercise plans. We also provide expert guidance on FDA approved anti-obesity medications including Zepbound (Tirzepatide) and Wegovy (Semaglutide), among others. We offer regular check-ins and adjustments to your treatment plan to ensure you’re on track, with timely responses to your questions, minimal wait times for appointments, and consistent care with Dr. Wilson.
If you’re in the St. Augustine area and looking for a primary care, sports medicine, or obesity medicine doctor, contact us to learn more about the practice. Visit FloridaDPC.com, email us at info@FloridaDPC.com, or call 904-650-2882.
This web site is provided for educational and informational purposes only and does not constitute the provision of medical advice or professional services. The information provided should not be used for diagnosing or treating individual health problems or diseases. Those seeking medical advice should consult with a licensed physician.Ready to become a Florida DPC member? Click here to register.
