Learn More About Semaglutide

Semaglutide is an injectable medication initially formulated for the treatment of type 2 diabetes, but it’s since become increasingly popular as a weight loss treatment. While the medication helps reduce blood glucose to normal levels, it also slows the passage of food through the stomach and reduces appetite, often resulting in weight reduction.

What is Semaglutide?

Semaglutide is a glucagon-like peptide 1 (GLP-1) analog used to manage type 2 diabetes and more recently weight loss, along withlifestyle changes, such as healthy and nutritional diets and increased physicalactivity. Semaglutide was developed by Novo Nordisk and approved by the FDA forsubcutaneous injection in December 2017. Semaglutide works by binding to andactivating the GLP-1 receptor, thereby stimulating insulin secretion andreducing blood glucose.

The subcutaneous injection is administered once weekly, making Semaglutide offer a competitive advantage over other drugs used to manage diabetes and overweight, which may require several daily doses. Clinical trials have determined that this drug reduces glycosylated hemoglobin (HbA1c)levels and reduces body weight. In June 2021, Semaglutide was approved by the FDA for chronic weight management in adults with general obesity.

Pharmacodynamics

Semaglutide reduces HbA1c, systolic blood pressure, and body weight. After 12 weeks of treatment, Semaglutide decreased fasting and postprandial glucose by increasing insulin production and decreasing glucagon secretion (which is normally associated with increases in blood sugar). Semaglutide also lowers fasting triglycerides and VLDL cholesterol, exerting beneficial effects on cardiovascular health.

Mechanism of action

Mechanism of glycemic control

GLP-1 is a physiological hormone that promotes glycemic control via several different mechanisms, including insulin secretion, slowing gastric emptying, and reducing postprandial glucagon secretion. The homeostasis of glucose is dependent on hormones such as insulin and amylin, which are secreted by the beta cells of the pancreas. Semaglutide is 94% similar to humanGLP-1. Analogs of this hormone such as Semaglutide stimulate the synthesis of insulin by stimulating pancreatic islet cells and reducing glucagon secretion. They directly bind with selectivity to the GLP-1 receptor, causing various beneficial downstream effects that reduce blood glucose in a glucose-dependent fashion.

Mechanism of cardiovascular benefit and weight loss

In hypercholesterolemia (high cholesterol), Semaglutide reduces the progression of atherosclerosis (thickening or hardening of the arteries caused by a buildup of plaque in the inner lining of an artery) via decreased gut permeability and decreased inflammation. Weight loss occurs via the reduction of appetite and food cravings after Semaglutide administration.

Route of elimination

This drug is mainly cleared by the kidneys and is found excreted in both the urine and feces. The main elimination route is the urine by corresponding to 53% of an ingested radiolabeled dose, with 18.6%found in the feces. A smaller amount of 3.2% was found to be exhaled. Hepatic impairment does not appear to affect the clearance of this drug and dose adjustments are not required in patients with decreased liver function.

Half-life

One of the major properties of Semaglutide is its long half-life of 168 hours. The long half-life is attributed to its albumin(most abundant circulating protein found in plasma) binding. This lowers the renal clearance and protects Semaglutide from metabolic breakdown.

Semaglutide Side Effects: 

• Nausea

• Vomiting

• Diarrhea

• Abdominal pain

• Constipation

• Headaches

Strategies for reducing or managing side effects include a slow titration(which means adjusting the dose), adequate hydration and use of medication for symptom control as needed. Sometimes, the temperature of food can affect nausea. Cold or room temperature meals might be more tolerable than hot meals, as they often have less aroma, which can trigger nausea. Ginger is a natural remedy that has been shown to reduce nausea. Consider adding ginger supplements or incorporating ginger into your diet.

Serious adverse effects include:

• Pancreatitis (inflammation of the pancreas)

• Changes in vision

• Low blood sugar

• Kidney problems or kidney failure

• Serious allergic reactions

• Gallbladder problems

If you are taking Semaglutide and experience any of the following symptoms, you should reach out to your health care provider immediately or seek emergency medical care:

• Ongoing pain starting in the upper left or middle of the abdomen that spreads to the back, with or without vomiting

• Rash, itchiness, swelling of the eyes, face, mouth, tongue or throat and difficulty breathing/swallowing

• Decreased urine output or edema (swelling of legs, ankles or feet)

• Changes in vision

• Dizziness and/or fainting

• Upper abdominal pain, fever, jaundice or clay-colored stool

• Rapid heartbeat

What should I do if I forget a dose?

If you are using Semaglutide injection, inject the missed dose as soon as you remember it. However, if 5 days or more have passed since the missed dose, skip the missed dose and continue your regular dosing schedule. Do not inject a double dose to make up for a missed one.

 

Risks of Semaglutide 

Do not take Semaglutide if you are pregnant or breastfeeding, or if you or anyone in your family has a history of medullary thyroid cancer (MTC), a rare type of thyroid cancer, or a history of multiple endocrine neoplasia type 2 (MEN 2), a rare endocrine condition. Let your doctor know if you have a history of pancreatitis or heavy alcohol consumption, as both can precipitate pancreatitis.

Additionally, if you’re taking Semaglutide in addition to other medications to lower your blood glucose levels, your dose may need to be lowered when starting (or increasing) Semaglutide to prevent hypoglycemia (very low glucose levels). Semaglutide, and other anti-obesity medications, are FDA-approved for long-term weight management because obesity is a chronic disease, just like hypertension (high blood pressure) and type 2diabetes

What should I know about storage and disposal of this medication?

Keep this medication in the container it came in and out of reach of children. Store it away from light and heat. Store unused Semaglutide in the refrigerator (36°F to 46°F [2°C to 8°C]) Do not freeze. Do not use Semaglutide if it has been frozen. When traveling, store your medication in a cold container with ice packs to ensure maintenance of adequate temperature, put it in the refrigerator as soon as one becomes available. Do not leave medication in a car, glove compartment or any other hot place.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. 

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Dispose of needles and syringes in puncture resistant containers to avoid accidental puncture and always keep them out of the reach of children.

 

The Takeaway

Semaglutide offers a promising path to weight loss, especially when combined with balanced dietary choices and an active lifestyle. By understanding what to eat, managing side effects, and incorporating consistent lifestyle changes, you can navigate your weight loss journey with absolute confidence. 

References

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3.        Centers for Disease Control and Prevention. (2024, May 15). Diabetes basics. Centersfor Disease Control and Prevention. https://www.cdc.gov/diabetes/about/

4.        FDA Approved Drug Products: OZEMPIC (semaglutide)injection, for subcutaneous use

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6.        Moman, R. N.(2022, December 26). Physiology, Albumin. StatPearls [Internet].https://www.ncbi.nlm.nih.gov/books/NBK459198/#:~:text=Albumin%20is%20the%20most%20abundant,to%2015%20gm%20per%20day.

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