Semaglutide
Recently semaglutide has garnered a significant amount of attention in the media and online, making headlines due to its remarkable efficacy in weight management. It is an active ingredient found in popular prescription medications such as Ozempic or Wegovy that works by mimicking a glucagon - like - peptide -1 (GLP-1), a naturally occurring hormone in the body. Due to this unique ability, semaglutide emerged as a key player in obesity and diabetes management.
In this article we will provide a focused review of semaglutide, covering its mechanism, benefits, side effects and uses in modern medicine.
How Does it Work?
In order to understand how semaglutide works let's take a look at GLP-1.
GLP -1 is a hormone produced by the small intestine in response to a meal. Its primary action is to stimulate the body to produce more insulin and reduce the amount of glucose (sugar). The presence of this hormone across multiple organs such as the pancreas, heart, kidney, lungs and the brain allows it to exert a wide range of physiological effects including reduced blood pressure and improved cardiovascular performance. In addition to its numerous metabolic functions, GLP-1 aids in proper digestion and absorption of nutrients by regulating the rate of stomach emptying and slowing down the gut motility. In higher amounts, it appears to interact with certain parts of the brain that regulate appetite and satiety. Consequently creating a feeling of fullness and reduced overall food intake.
Naturally occurring GLP-1 has a very short half-life, with its effect dissipating within 1-2 minutes due to rapid metabolic breakdown and elimination processes facilitated by our kidneys. Semaglutide has been formulated to extend its duration from minutes to days and even weeks allowing it to be present in the body for about 5 weeks after the last dose.
How is it available?
Currently there are three semaglutide-containing products on the market that are FDA approved.
Ozempic: Once weekly injectable medication available in 0.25 mg, 0.5 mg, 1 mg and 2 mg doses. Although it gained its popularity as a weight loss drug, it has only been indicated as an adjunct to diet and exercise in treatment of type -2 diabetes. Furthermore it has shown to reduce the risk of heart attack and stroke in diabetic patients suffering from heart disease.
Rybelsus: The only oral formulation available in 3 mg, 7 mg, and 14 mg doses. Similarly to Ozempic it has only been approved to be used for treatment of type - 2 diabetes in addition to diet and exercise. In order to be fully effective this medication must be taken at least 30 minutesbefore the first food, beverage, or other oral medications of the day with no more than 4 ounces of plain water only.
Wegovy: The only semaglutide product approved for chronic weight management, intended to work in tandem with reduced calorie diet and exercise. It is available as once weekly injectable medication available in 0.25 mg, 0.5 mg, 1 mg, 1.7 mg and 2.4 mg dose.
Who should take it?
Semaglutide is indicated for treatment of obesity and type 2 diabetes. Although Wegovy is the only product FDA approved for weight management, Ozempic and Rybelsus have been prescribed “off -label” for this purpose due to their effectiveness in promoting weight loss.
Semaglutide is recommended for:
Adults with an initial body mass index (BMI) of
30 kg/m2 or greater (obesity) or
27 kg/m2 or greater (overweight) in the presence of at least one weight-related condition such as high blood pressure or high cholesterol.
Pediatrics aged 12 years and older with an initial BMI at the 95th percentile or greater for age and gender.
Who shouldn’t take it ?
Semaglutide is not recommended as first-line therapy for patients inadequately controlled on diet and exercise. This medication is not indicated for use in type 1 diabetes, pregnancy and has not been studied in patients with a history of pancreatitis. Multiple semaglutide products will not provide additional benefit and should not be taken together.
What are the risks?
Semaglutide was first approved for medical use in 2017. Since then it has undergone numerous trials assessing its safety and efficacy in patients with obesity and type - 2 diabetes. While all medications can cause side effects for some, the potential risks may outweigh the benefits.
Currently this medication carries a black box warning of increased risk of thyroid C - cell tumors including medullary thyroid carcinoma (MTC). Its use is contraindicated in patients with personal or family history of MTC or in patients with Multiple Endocrine Neoplasia Syndrome type 2 (MEN 2). While the carcinogenic potential of Semaglutide is very rare, routine monitoring for signs and symptoms of thyroid tumors is recommended.
Other rare but serious side effects include:
Kidney problems such as inability to urinate, change in urination or blood in urine.
Gallbladder issues such as pain in the upper right abdominal area, pain in right shoulder or between shoulder blades, change in stool, dark urine or yellow skin and eyes.
Severe dizziness and drowsiness
Pancreatitis which can present as severe stomach pain, severe back pain or severe upset stomach and vomiting.
Behavioral changes such as worsening mood, depression or thoughts of suicide.
Aversion to food or water.
Allergic reaction, including rash, hives, itching ,redness and swelling, wheezing or trouble breathing.
Common side effects include:
Gastrointestinal issues: nausea, vomiting, bloating, burping, gassiness, constipation or diarrhea.
Decreased appetite
Headache
Heartburn
Tiredness or weakness.
The side effects listed are not all side effects that may occur. However gastrointestinal issues such as nausea and vomiting are most commonly reported. In order to reduce the incidence of these it is recommended to start at the lowest available dose and slowly increase the dose over time to let the body get used to the medication.
Ultimately….
Semaglutide has demonstrated a high efficacy in regard to weight loss and treatment of type 2 diabetes. Its ability to mimic GLP-1 and exert multiple beneficial effects on glucose metabolism, appetite regulation and cardiovascular health makes it a versatile and an effective therapeutic option. It is a great alternative to patients considering bariatric surgery, however it requires a long term commitment as weight regain is likely to occur once treatment is stopped. Due to its multifaceted approach to metabolic health currently higher doses of semaglutide are being studied offering new options for obesity management.
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Ozempic. Package insert. Novo Nordisk. 2017.
Rybelsus. Package insert. Novo Nordisk. 2019.
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Wegovy. Package insert. Novo Nordisk. 2023.
