Overview of Semaglutide

Dosage Strengths of Semaglutide

Semaglutide 2.5mg/mL (5mg/2mL per vial)

Mechanism of Action

Semaglutide is an incretin mimetic drug that activates the glucagon-like peptide-1 (GLP-1) receptor by binding to it. GLP-1 is an important regulator of glucose homeostasis that is released by the gut after the consumption of carbohydrates or fats. In patients with Type 2 diabetes, GLP-1 levels are decreased in response to oral glucose. GLP-1 enhances insulin secretion and synthesis and inhibits glucagon secretion, which leads to a reduction in blood glucose levels. Semaglutide’s long half-life is due to its binding to albumin, which protects it from metabolic degradation. The drug reduces blood glucose levels by stimulating insulin secretion and inhibiting glucagon secretion in a glucose-dependent manner. Additionally, it delays gastric emptying during the early postprandial phase, which contributes to its blood glucose-lowering effect.

General Information

Semaglutide is a medication used to improve glycemic control in adults with type 2 diabetes mellitus (T2DM). It is a synthetic glucagon-like peptide-1 receptor agonist (GLP-1 RA) and belongs to a class of antidiabetic agents called incretin mimetics. GLP-1 is an endogenous compound that improves glycemic control once released into the circulation via the gut. Semaglutide is available as a subcutaneous injection.

First-line T2DM therapy depends on comorbidities, patient-centered treatment factors, and management needs and generally includes metformin and comprehensive lifestyle modification. Therapy with a GLP-1 RA or sodium-glucose cotransporter 2 inhibitor (SGLT2 inhibitor) that has proven cardiovascular benefit is recommended for initial therapy, with or without metformin based on glycemic needs, in patients with indicators of high-risk or established cardiovascular disease.



This generalized information is a limited summary of diagnosis, treatment, and/or medication information. It is not meant to be comprehensive and should be used as a tool to help the user understand and/or assess potential diagnostic and treatment options. It does NOT include all information about conditions, treatments, medications, side effects, or risks that may apply to a specific patient. It is not intended to be medical advice or a substitute for the medical advice, diagnosis, or treatment of a health care provider based on the health care provider’s examination and assessment of a patient’s specific and unique circumstances. Patients must speak with a health care provider for complete information about their health, medical questions, and treatment options, including any risks or benefits regarding use of medications. This information does not endorse any treatments or medications as safe, effective, or approved for treating a specific patient. UpToDate, Inc. and its affiliates disclaim any warranty or liability relating to this information or the use thereof. The use of this information is governed by the Terms of Use, available at https://www.wolterskluwer.com/en/know/clinical-effectiveness-terms. Semaglutide Vial for injection


WARNING This drug has been shown to cause thyroid cancer in some animals. It is not known if this happens in humans. If thyroid cancer happens, it may be deadly if not found and treated early. Call your doctor right away if you have a neck mass, trouble breathing, trouble swallowing, or have hoarseness that will not go away.; Do not use this drug if you have a health problem called Multiple Endocrine Neoplasia syndrome type 2 (MEN 2), or if you or a family member have had thyroid cancer.


It is used to help with weight loss in certain people.


If you are allergic to this drug; any part of this drug; or any other drugs, foods, or substances. Tell your doctor about the allergy and what signs you had.; If you have ever had pancreatitis.; If you have or have ever had depression or thoughts of suicide.; If you are using another drug that has the same drug in it.; If you are using another drug like this one. If you are not sure, ask your doctor or pharmacist.This is not a list of all drugs or health problems that interact with this drug.Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this drug with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.


Tell all of your health care providers that you take this drug. This includes your doctors, nurses, pharmacists, and dentists. ; Follow the diet and workout plan that your doctor told you about.; Have blood work checked as you have been told by the doctor. Talk with the doctor.; Talk with your doctor before you drink alcohol.; Kidney problems have happened. Sometimes, these may need to be treated in the hospital or with dialysis.; If you cannot drink liquids by mouth or if you have upset stomach, throwing up, or diarrhea that does not go away; you need to avoid getting dehydrated. Contact your doctor to find out what to do.

Dehydration may lead to new or worse kidney problems.; Do not share a vial with another person even if the syringe has been changed. Sharing these vials may pass infections from one person to another. This includes infections you may not know you have.; If you are planning on getting pregnant, talk with your doctor. You may need to stop taking this drug at least 2 months before getting pregnant.; If you have high blood sugar (diabetes), you will need to watch your blood sugar closely.; Weight loss during pregnancy may cause harm to the unborn baby. If you get pregnant while taking this drug or if you want to get pregnant, call your doctor right away.; Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.


Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect: Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.; Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.; Signs of gallbladder problems like pain in the upper right belly area, right shoulder area, or between the shoulder blades; change in stools; dark urine or yellow skin or eyes; or fever with chills.; New or worse behavior or mood changes like depression or thoughts of suicide.; Very bad dizziness or passing out.; A fast heartbeat.; Change in eyesight.; Low blood sugar can happen. The chance may be raised when this drug is used with other drugs for diabetes. Signs may be dizziness, headache, feeling sleepy or weak, shaking, fast heartbeat, confusion, hunger, or sweating. Call your doctor right away if you have any of these signs. Follow what you have been told to do for low blood sugar. This may include taking glucose tablets, liquid glucose, or some fruit juices.; Severe and sometimes deadly pancreas problems (pancreatitis) have happened with this drug. Call your doctor right away if you have severe stomach pain, severe back pain, or severe upset stomach or throwing up.


All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away: Constipation, diarrhea, stomach pain, upset stomach, or throwing up.; Headache.; Feeling dizzy, tired, or weak.; Burping.; Gas. These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-332-1088. You may also report side effects at https://www.fda.gov/medwatch.


Use this drug as ordered by your doctor. Read all the information given to you. Follow all instructions closely.; It is given as a shot into the fatty part of the skin on the top of the thigh, belly area, or upper arm.; If you will be giving yourself the shot, your doctor or nurse will teach you how to give the shot. ; Take with or without food.; Take the same day each week.; Move the site where you give the shot with each shot.; Do not use if the solution is cloudy, leaking, or has particles.; Do not use if solution changes color.; Wash your hands before and after use.; Keep taking this drug as you have been told by your doctor or other health care provider, even if you feel well.

WHAT DO I DO IF I MISS A DOSE? Take a missed dose as soon as you think about it and go back to your normal time.; If it is less than 48 hours until your next dose, skip the missed and go back to your normal time.; Do not take 2 doses within 48 hours of each other.; If you miss 2 doses, call your doctor.


Store vials in a refrigerator. Do not freeze.; Do not use if it has been frozen.; You may store unopened containers at room temperature. If you store at room temperature, throw away any part not used after 28 days.; Store in the original container to protect from light.; Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.; Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.


If your symptoms or health problems do not get better or if they become worse, call your doctor. ; Do not share your drugs with others and do not take anyone else’s drugs.; This drug comes with an extra patient fact sheet called a Medication Guide. Read it with care. Read it again each time this drug is refilled. If you have any questions about this drug, please talk with the doctor, pharmacist, or other health care provider.; If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.


The use of semaglutide for weight management or obesity is not recommended during pregnancy as it does not offer any potential benefit to pregnant women, and may even cause harm to the fetus due to potential hazards of maternal weight loss. The American Association of Clinical Endocrinologists and American College of Endocrinology’s Obesity Clinical Practice Guidelines advise against the use of weight loss medications during pregnancy and recommend contraception for patients of childbearing potential who are receiving semaglutide for weight reduction. In case of pregnancy, patients should discontinue semaglutide use.

There is a lack of adequate data and clinical studies on the use of semaglutide for treating type 2 diabetes mellitus (T2DM) in pregnant women. Its use during pregnancy should only be considered if the potential benefits outweigh the potential risks to the fetus. Studies conducted on rats, rabbits, and cynomolgus monkeys have shown embryofetal mortality, structural abnormalities, and growth alterations in fetuses at maternal exposures below the recommended human dose. Poorly controlled diabetes during pregnancy also poses risks to the fetus.


Caution should be exercised when using injectable semaglutide during lactation, while oral semaglutide therapy is not recommended. The effects of semaglutide on human milk and its impact on the breastfed infant and milk production are unknown. However, lactating rats have shown semaglutide in their milk at levels lower than in maternal rat plasma. Absorption enhancer Salcaprozate sodium (SNAC) and its metabolites were found in lactating rats’ milk, but their presence in human milk is unknown. Infants have lower clearance of SNAC, and higher levels may occur in neonates and infants. Since the potential for serious adverse reactions in the breastfed infant is unknown due to the possible accumulation of SNAC from breastfeeding, advise patients to avoid breastfeeding during treatment with oral semaglutide tablets. If insulin therapy is required after discontinuing semaglutide and blood glucose is not controlled on diet and exercise alone, it should be considered. Other oral hypoglycemics such as acarbose, metformin, tolbutamide, or glyburide can be considered as possible alternatives during breastfeeding. However, nursing infants should be monitored for signs of hypoglycemia such as increased fussiness or somnolence if any oral hypoglycemics are used during breastfeeding.

Common Side Effects/Adverse Reactions

During monotherapy trials for type 2 diabetes mellitus (T2DM) using semaglutide injection, there were no reports of severe hypoglycemia (requiring the assistance of another person) in either the treatment group or the placebo group. However, documented symptomatic hypoglycemia (glucose of 70 mg/dL or less) was reported in 1.6% to 3.8% of patients receiving semaglutide injection, compared to 0% of patients receiving placebo. Furthermore, severe or blood glucose confirmed symptomatic hypoglycemia (glucose of 56 mg/dL or less) was not reported in any of the patients receiving semaglutide monotherapy, whereas it was reported in 1.6% of patients receiving placebo.

When semaglutide was added on to basal insulin with or without metformin, 1.5% of semaglutide-treated patients experienced severe hypoglycemia, and documented symptomatic hypoglycemia was reported in 16.7% to 29.8% of patients. Severe or blood glucose confirmed symptomatic hypoglycemia was reported in 8.3% to 10.7% of patients receiving semaglutide. However, when semaglutide was used in combination with a sulfonylurea, the frequency of hypoglycemia increased. Severe hypoglycemia occurred in 0.8% and 1.2% of patients when semaglutide 0.5 mg and 1 mg, respectively, were given with a sulfonylurea, and documented symptomatic hypoglycemia occurred in 17.3% and 24.4% of patients when semaglutide 0.5 mg and 1 mg, respectively, were coadministered with a sulfonylurea. Severe or blood glucose confirmed symptomatic hypoglycemia occurred in 6.5% and 10.4% of patients when semaglutide 0.5 mg and 1 mg, respectively, were given with a sulfonylurea.

In monotherapy trials using semaglutide oral tablets for T2DM, severe hypoglycemia was reported in 1% of patients receiving the 7 mg tablets and 0% of patients receiving the 14 mg tablets or placebo. A blood glucose level of 54 mg/dL or less occurred in 1% of patients receiving placebo and 0% of the semaglutide oral treatment groups. When semaglutide tablets were added on to metformin and/or sulfonylurea, basal insulin alone, or metformin in combination with basal insulin in patients with moderate renal impairment, no reports of severe hypoglycemia were made. However, a blood glucose level of 54 mg/dL or less occurred in 6% of patients receiving the 14 mg tablets, 3% of patients receiving placebo, and 0% of patients receiving the 7 mg tablets.

In trials where semaglutide was added on to insulin with or without metformin, severe hypoglycemia was reported in 1% of patients receiving the 14 mg tablets, 1% of patients receiving placebo, and 0% of patients receiving the 7 mg tablets. A blood glucose level of 54 mg/dL or less was reported in 26% of patients receiving the 7 mg tablets, 30% of patients receiving the 14 mg tablets, and 32% of those receiving placebo.


Store this medication in a refrigerator at 36° F to 46° F (2° C to 8° C) and away from heat, moisture and light. Keep all medicine out of the reach of children. Throw away any unused medicine after the beyond-use date. Do not flush unused medications or pour down a sink or drain.

1. Davies MJ, D’Alessio DA, Fradkin J, et al. Management of hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2018;41:26

2. Garvey WT, Mechanick JI, Brett EM, et al; Reviewers of the AACE/ACE Obesity Clinical Practice Guidelines. American Association of Clinical Endocrinologists and American College of Endocrinology comprehensive clinical practice guidelines.

3. Food and Drug Administration (US FDA) Drug Medwatch-FDA investigating reports of possible increased risk of pancreatitis and pre-cancerous findings of the pancreas from incretin mimetic drugs for type 2 diabetes.

4. American Diabetes Association. Standards of Medical Care in Diabetes – 2022. Diabetes Care. 2022; 45(Suppl 1):S1-S270. Available at: https://diabetesjournals.org/care/issue/45/Supplement_1