What is semaglutide?

Semaglutide is a peptide medication that belongs to a class called glucagon-like peptide-1 receptor (GLP-1) agonists. GLP-1 is a hormone released by the intestines in response to food to aid in glucose metabolism and satiety (feeling full after a meal). GLP-1 decreases the rate at which food empties from the stomach, which reduces calorie intake and promotes weight loss.^1 The body clears GLP-1 made by the intestinal cells within minutes.^2 Semaglutide is given as a weekly injection and maintains elevated levels of GLP-1 for seven days.^3  

How is semaglutide different than Ozempic or Wegovy?

Wegovy and Ozempic are brand-name medications that utilize semaglutide for different reasons. The FDA approved Ozempic for the management of Type 2 diabetes. Clinical studies revealed that patients with diabetes who took Ozempic lost weight. Subsequent trials in overweight and obese adults demonstrated efficacy as a weight loss agent, and Wegovy was approved for this indication by the FDA.^4 The semaglutide that Nimbus uses is compounded in a specialty pharmacy because semaglutide is on the FDA shortage list. The FDA shortage list lists medications where demand exceeds the available supply. Compounding pharmacies can compound a therapeutically equivalent semaglutide and distribute that to patients with a legitimate prescription.^5 

How effective is semaglutide for weight loss?

Semaglutide can be a very effective agent for weight loss; however, patients with diabetes lose less weight than patients without diabetes.^6 In a recent two-year trial of semaglutide vs. placebo, the participants in the semaglutide group lost an average of 15.2% of their initial body weight compared to 2.6% for placebo.^7 However, once semaglutide is stopped, significant weight regain can occur. One year after stopping semaglutide and lifestyle interventions, participants regained 11.6% of their body weight for a net loss of 5.6% of initial body weight. A regression was also seen in cardiometabolic markers that had improved while on semaglutide therapy.^8

For this reason, we do not believe in treating with semaglutide alone. Our Discover You program has robust information regarding the big five of lifestyle medicine (mindset, nutrition, exercise, stress management, and sleep). These are essential to creating a mindset shift to ensure long-term behavioral changes and sustainable weight loss. The STEP 3 trial showed a significant improvement in body weight (a loss of 5.7% of initial body weight) in the placebo group placed in an energy deficit and receiving behavioral counseling.^9

Who is not a good candidate for semaglutide?
Semaglutide can interact with medications used for diabetes. Patients on diabetes medications other than metformin are at a higher risk of developing low blood sugars. Also, patients with diabetes complications of the eye should not use semaglutide. Semaglutide should not be used in patients with a history of pancreatitis, acute kidney injury, or gallbladder disease, as semaglutide may worsen these conditions. Patients with a family or personal history of multiple endocrine neoplasia syndrome or medullary thyroid cancer are not candidates for semaglutide therapy.^3 Women who are pregnant or trying to become pregnant are not candidates for semaglutide therapy. 

What are the adverse effects of semaglutide

In a two-year trial of semaglutide for weight loss, adverse effects leading to discontinuation of the medication occurred in 5.9% of the participants. The most common adverse effects were nausea (53.3%), diarrhea (34.9%), constipation (30.9%), vomiting (30.3%), abdominal pain (13.2%), allergic reactions (15.1%), dyspepsia (13.2%), flatulence (13.2%), gastroenteritis (13.2%), and belching (11.2%). Rare events included low blood sugar (2.6%),  gallbladder disorders (2.6%), and injection site reactions (6.6%). No events of pancreatitis or acute renal failure were seen in this study, but pancreatitis (inflammation of the pancreas) and renal failure due to dehydration from vomiting, diarrhea, or inadequate hydration are possible adverse effects.^7,10 

The gastrointestinal adverse effects of semaglutide are usually transient, mild, and resolve by the time the maintenance dose is reached. Persistent or severe nausea, vomiting, diarrhea, or abdominal pain is worrisome. Stop taking semaglutide if you experience persistent or severe nausea, vomiting, diarrhea, or abdominal pain, and seek immediate medical attention. Severe abdominal pain, nausea, or vomiting can be a sign of pancreatitis, which may require hospitalization for treatment. Do not “push through” repeated bouts of diarrhea, nausea, and vomiting, as this can lead to severe dehydration with serious consequences such as acute renal failure. Maintaining adequate hydration is essential for clinical success with semaglutide.

Using semaglutide without strength/resistance training and adequate protein intake can result in a significant loss of muscle mass. In two trials utilizing semaglutide, the participants saw 39% and 40% of their total weight loss be loss of muscle mass.^4,11 

Are there any tips to minimize semaglutide adverse effects?

To prevent muscle loss, we recommend maintaining a protein intake of approximately 0.8 g /lb of body weight and performing resistance training two to three times a week for a total of 75 minutes a week. We suggest working with a personal trainer or fitness professional to fine-tune your workout regimens to your individual needs.^12 As we age, sarcopenia (loss of muscle mass) is associated with an increased risk of cardiovascular disease, falls, dementia, diabetes, kidney dysfunction, some cancers, and poor disease prognosis.^13

Semaglutide decreases the rate at which the stomach empties into the intestines, thus increasing satiety and fullness. Overeating can lead to nausea, vomiting, diarrhea, and abdominal pain. Tips to prevent overeating include eating slowly, eating smaller portions, limiting snacking and eating only when hungry, eating until you feel like you are 80% full, eating smaller, more frequent meals, avoiding using a straw to reduce swallowing air, limiting liquid intake during meals or 30 to 60 minutes before or after meals, limiting eating right before bed or eating and then lying down, and trying not to perform vigorous activity directly after a meal. Mint or ginger-based drinks and avoiding strong smells within 30 minutes of taking semaglutide may help to reduce nausea. 

If an adverse effect persists at a specific dose but is not present at a lower dose, we recommend remaining at the lower dose.

Are there additional weight loss resources you recommend?
I recommend the book Fat Loss Forever by Dr. Layne Norton. It is an excellent book on creating sustainable habits with nutrition and exercise to lose weight and keep it off. The Carbon Diet App is a great app that provides calorie counting and coaching. As you lose weight and gain muscle, your calorie needs will change. The Carbon Diet app offers guidance on calories and macros to maintain muscle mass while eating a diet below maintenance calories (a calorie deficit). Another good book on nutrition is Flexible Dieting by Alan Aragon. 

How do I use semaglutide?

Semaglutide is given as a subcutaneous (under the skin) injection once a week. Store semaglutide in the refrigerator away from light, heat, and moisture. Unused or expired medication should be thrown away and not flushed down the toilet or placed down the sink. The starting dose is 0.25 mg per week, which is increased as tolerated every month until the maximum dose of 2 mg per week is achieved. The maximum weight loss is achieved between six to twelve months of therapy.^7

How much medication to draw up in the syringe depends on your vial concentration and prescribed dose. See the instructions that come in your Nimbus package for accurate administration instructions.

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9 Wadden TA, Bailey TS, Billings LK, et al. Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity: The STEP 3 Randomized Clinical Trial. JAMA. 2021;325(14):1403-1413. doi:10.1001/jama.2021.1831
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Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The
STEP 8 Randomized Clinical Trial. JAMA. 2022;327(2):138-150. doi:10.1001/jama.2021.23619
11 McCrimmon RJ, Catarig AM, Frias JP, et al. Effects of once-weekly semaglutide vs once-daily
canagliflozin on body composition in type 2 diabetes: a substudy of the SUSTAIN 8 randomised
controlled clinical trial. Diabetologia. 2020;63(3):473-485. doi:10.1007/s00125-019-05065-8
12 Gorgojo-Martínez JJ, Mezquita-Raya P, Carretero-Gómez J, et al. Clinical Recommendations
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