Ozempic FDA Approval History | Side Effect Warning Label Change

How did Ozempic medication get approved by the FDA?

Below you will find a comprehensive explanation of Ozempic FDA approval history

• • • On December 5, 2016, Novo Nordisk formally declared a submission of Ozempic to the Food and Drug Administration (FDA) to obtain regulatory approval of Ozempic as weekly injectable Semaglutide to treat type 2 diabetes. Company announcement
    • On December 5, 2016, Novo Nordisk Inc. presented NDA 209637, asking the FDA to approve Ozempic Semaglutide 0.5 mg or 1 mg injection to complement diet and exercise to improve glycemic control in person over 18 years old suffering through type 2 diabetes mellitus.
    • On December 5, 2017, the FDA green lighted NDA 209637.32. (FDA Ozempic approval). The approval letter was signed off by Mary T. Thanh Hai, M.D., the Deputy Director Office of Drug Evaluation II Office of New Drugs, Center for Drug Evaluation and Research.
    • On March 20, 2019, Novo Nordisk Inc. presented an additional drug application for Ozempic which was supplemental, in nature. Novo’s application was seeking more extensive marketing bandwidth for Ozempic by allowing marketing of Ozempic to resolve major adverse cardiovascular events in persons over 18 suffering through type 2 diabetes and cardiovascular disease.
    • On January 16, 2020, the FDA approved the supplemental request pertaining to Ozempic treatment of cardiovascular disease.
    • On May 28, 2021,  Novo Nordisk Inc. requested approval for a larger 2 mg dose of Ozempic medication injection.
    • On March 28, 2022, the FDA greenlighted Ozempic approval for a larger dose.

Ozempic warning label updates since the FDA approved Ozempic in 2017:

Below you will find a comprehensive explanation of FDA Ozempic warning label changes from 2017-2026.

• • • On December 5, 2017 the FDA approved Ozempic (FDA Ozempic approval). The first warning label warned patients about side effects such as: nausea, thyroid c-cell tumors, constipation, risks of pancreatitis, diabetic retinopathy complications, and hypoglycemia when used with insulin and potential kidney issues caused by dehydration. The FDA required a box warning (formerly a black box warning) concerning the link between Semaglutide and the likelihood of thyroid c-cell tumors, which specifically includes medullary thyroid carcinoma (MTC).
    • January 16, 2020:  (Approved for cardiovascular health) Ozempic was approved to treat cardiovascular health issues. New verbiage was added specifically stating that Ozempic could reduce the risk of heart attack, stroke or death in people with type two diabetes suffering through heart disease. The Ozempic label was amended to read that Ozempic is a medicine used, “to reduce the risk of major cardiovascular events such as heart attack, stroke or death in adults with type 2 diabetes mellitus with known heart disease.”
    • April 12, 2021:  (Warning about hypoglycemia) Important alterations concerning the chance of hypoglycemia and serious allergic reactions, like anaphylaxis.  Novo warned of the following adverse reactions when Ozempic is combined with insulin: “Hypersensitivity: anaphylaxis, angioedema, rash, urticaria.” The label was changed to read (changes underlined): “Patients receiving OZEMPIC in combination with an insulin secretagogue (e.g., sulfonylurea) or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia. The risk of hypoglycemia may be lowered by a reduction in the dose of sulfonylurea (or other concomitantly administered insulin secretagogue) or insulin. Inform patients using these concomitant medications of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia.”

• • • March 28, 2022: (Gallbladder disease) The Ozempic label was modified to add acute gallbladder disease (cholelithiasis and cholecystitis). A new section was added to the Ozempic label concerning acute gallbladder disease which reads (changes underlined): “Acute events of gallbladder disease such as cholelithiasis or cholecystitis have been reported in GLP-1 receptor agonist trials and post marketing. In placebo-controlled trials, cholelithiasis was reported in 1.5% and 0.4% of patients-treated with OZEMPIC 0.5 mg and 1 mg, respectively. Cholelithiasis was not reported in placebo- treated patients. If cholelithiasis is suspected, gallbladder studies and appropriate clinical follow-up are indicated.” The March 2022 label change also includes warnings about different side effects: “OZEMPIC may cause serious side effects, including:…  gallbladder problems. Gallbladder problems have happened in some people who take OZEMPIC. Tell your healthcare provider right away if you get symptoms of gallbladder problems which may include: pain in your upper stomach (abdomen), fever, yellowing of skin or eyes (jaundice),clay-colored stools” The following adverse reactions were added to the label “Hepatobiliary: cholecystitis, cholecystectom”
    • October 6, 2022:  (Birth Defects and Miscarriages)The Ozempic label was modified by the FDA concerning birth defects and miscarriages (changes underlined). “In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. The estimated background risk of major birth defects is 6 to 10% in women with pre-gestational diabetes with a peri-conceptional HbA1c >7 and has been reported to be as high as 20 to 25% in women with a peri-conceptional HbA1c >10. The estimated background risk of miscarriage for the indicated population is unknown…Hypoglycemia and hyperglycemia occur more frequently during pregnancy in patients with pre-gestational diabetes. Poorly controlled diabetes during pregnancy increases the maternal risk for diabetic ketoacidosis, pre- eclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity.”
    • September 22, 2023:  (Gastrointestinal Disorders: Ileus) This update involves the risk of severe hypoglycemia and ileus was as adverse reaction. The U.S. Food & Drug Administration (FDA) required ileus (intestinal blockage) warnings on Ozempic medication labels. The FDA Ozempic warnings include ileus as an adverse reaction of Ozempic. Ileus was added in the section concerning post marketing experience. The label indicates that post marketing warnings result from victims’ reporting negative side effects to the drug. The warning label to this date includes an ileus (intestinal blockage) warning because of the risk of this severe gastrointestinal disorder. This warning was included as a result of post market reports, further studies and adverse event reports. The warnings on the label now include (changes underlined): “Gastrointestinal Disorders: Ileus, Hypersensitivity: anaphylaxis, angioedema, rash, urticaria, Hepatobiliary: cholecystitis, cholecystectomy” The September 2023 label modifications included (changes underlined): “OZEMPIC stimulates insulin release in the presence of elevated blood glucose concentrations. Patients receiving OZEMPIC in combination with an insulin secretagogue (e.g., sulfonylurea) or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia.”

• • • November 1, 2024:  (Pulmonary Aspiration)The Ozempic label was modified to add a warning concerning pulmonary aspiration during general anesthesia or deep sedation. The label now includes adverse reactions of: “Pulmonary Aspiration During General Anesthesia or Deep Sedation.” The label was modified in pertinent part that: “OZEMPIC may cause serious side effects, including: food or liquid getting into the lungs during surgery or other procedures that use anesthesia or deep sleepiness (deep sedation). OZEMPIC may increase the chance of food getting into your lungs during surgery orother procedures. Tell all your healthcare providers that you are taking OZEMPIC before you are scheduled to have surgery or other procedures.”

• • • January 2025: The Ozempic label was modified indicating that Ozempic is “not recommended in patients with severe gastroparesis.” The updated label does not warn that Ozempic can cause Gastroparesis! The FDA label change states in pertinent part: “Inform patients of the potential risk of severe gastrointestinal adverse reactions. Instruct patients to contact their healthcare provider if they have severe or persistent gastrointestinal symptoms“ The label was modified to notify victims of reports of severe pancreatitis as well as acute kidney injury. The label now states in pertinent part: “Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 receptor agonists, including Semaglutide“The FDA also required that the following adverse reactions on Ozempic label (changes underlined): Acute Pancreatitis, Acute Kidney Injury Due to Volume Depletion, Severe Gastrointestinal Adverse Reactions, Hepatobiliary: cholecystitis, cholecystectomy, Neurologic: dysesthesia Skin and Subcutaneous Tissue: alopecia.
    • October 2025:  Below you will find the FDA warnings with Additions and/or revisions from October 2025 underlined: “Use of OZEMPIC has been associated with gastrointestinal adverse reactions, sometimes severe. In OZEMPIC clinical trials, severe gastrointestinal adverse reactions were reported more frequently among patients receiving OZEMPIC (0.5 mg 0.4%, 1 mg 0.8%) than placebo (0%). Severe gastrointestinal adverse reactions have also been reported post marketing with GLP-1 receptor agonists. OZEMPIC is not recommended in patients with severe gastroparesis” In October 2025: The FDA also added and amended the following adverse reaction complications (changes underlined) “Gastrointestinal: ileus, intestinal obstruction, severe constipation including fecal impaction, Renal: acute kidney injury…. headache.

The FDA required a boxed warning on Ozempic for the RISK OF THYROID C-CELL TUMORS

The FDA issued a boxed warning (formerly known as a Black Box Warning) for Wegovy and Ozempic.  The FDA has required a boxed warning for Ozempic (Semaglutide) concerning the chance of thyroid C-cell tumors since Ozempic was approved on December 5, 2017. This FDA boxed warning warns patients concerning the link between Semaglutide and the likelihood of thyroid c-cell tumors, which specifically includes medullary thyroid carcinoma (MTC). MTC is a very rare type of thyroid cancer that is deadly. Boxed warnings are the most severe form of warning issued by the FDA. Boxed warnings are typically utilized by the FDA when a drugs complications can result in catastrophic harm or even death. These FDA warning were formerly known as “black box warnings.”

“WARNING: RISK OF THYROID C-CELL TUMORS See full prescribing information for complete boxed warning. In rodents, Semaglutide causes thyroid C-cell tumors. It is unknown whether OZEMPIC causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as the human relevance of Semaglutide-induced rodent thyroid C-cell tumors has not been determined (5.1, 13.1).OZEMPIC is contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk of MTC and symptoms of thyroid tumors.”