Victoza FDA Alerts

FDA Clarifies Policies for Compounders as National GLP-1 Supply Begins to Stabilize

October 2, 2024 -- The U.S. Food and Drug Administration has determined the shortage of tirzepatide injection, a glucagon-like peptide 1 (GLP-1) medication, has been resolved. Tirzepatide injection has been in shortage since 2022 due to increased demand.

FDA confirmed with the drug’s manufacturer that their stated product availability and manufacturing capacity can meet the present and projected national demand. Patients and prescribers may still see intermittent localized supply disruptions as the products move through the supply chain from the manufacturer and distributors to local pharmacies.

FDA reminds compounders of the legal restrictions on making copies of FDA-approved drugs

Compounded drugs are not approved by FDA. FDA-approved drugs go through FDA’s rigorous review for safety, effectiveness, and quality as part of the premarket approval process. Compounded drugs must meet conditions to qualify for exemptions under sections 503A and 503B of the Federal Food, Drug and Cosmetic (FD&C) Act. Among the conditions are:

• Section 503A of the FD&C Act includes restrictions on compounding drugs that are essentially copies of a commercially available drug. When a drug shortage is resolved, FDA generally considers the drug to be commercially available. Certain amounts are permissible under the law as long as the compounding is not done “regularly or in inordinate amounts.”
• Section 503B of the FD&C Act restricts outsourcing facilities from making compounded drugs that are essentially a copy of one or more FDA-approved drugs. Among other things, this means the compounded drug may not be identical or nearly identical to an FDA-approved drug unless the approved drug is on FDA’s drug shortage list.

Current shortage status of GLP-1 products (as of October 02, 2024):

• Tirzepatide injection: Shortage resolved.
• Dulaglutide injection: In shortage.
• Semaglutide injection: In shortage. Manufacturer has reported all but one of the presentations are available.
• Liraglutide injection: In shortage. Manufacturer has reported 2 presentations are available, and three have limited availability.

The agency will continue to work with manufacturers to help resolve the current shortages, and, as shortages resolve, will closely monitor the situation and provide any assistance we can to help manufacturers ensure an adequate supply. Before determining that a shortage is resolved, FDA considers a variety of factors, including the company's ability to meet current and historical demand, the amount in a manufacturer’s stock, affected market share, ability of alternate manufacturers to cover the demand, and confirmed market stabilization. Please visit FDA’s Drug Shortages Database for the most recent information on the status of GLP-1 medicines and other drugs in shortage.

Source: FDA

Drug Safety Communication: Certain Type of Medicines Approved for Type 2 Diabetes and Obesity - Update on FDA’s Ongoing Evaluation of Reports of Suicidal Thoughts or Actions

ISSUE: The FDA has been evaluating reports of suicidal thoughts or actions in patients treated with a class of medicines called glucagon-like peptide-1 receptor agonists (GLP-1 RAs; see the list in Table 1 below). These medicines are used to treat people with type 2 diabetes or to help those with obesity or overweight to lose weight. FDA's preliminary evaluation has not found evidence that use of these medicines causes suicidal thoughts or actions.

Over the last several months, the FDA has conducted detailed reviews of reports of suicidal thoughts or actions received in the FDA Adverse Event Reporting System (FAERS). Because the information provided was often limited and because these events can be influenced by other potential factors, the FDA determined that the information in these reports did not demonstrate a clear relationship with the use of GLP-1 RAs. Similarly, the FDA's reviews of the clinical trials, including large outcome studies and observational studies did not find an association between use of GLP-1 RAs and the occurrence of suicidal thoughts or actions. However, because of the small number of suicidal thoughts or actions observed in both people using GLP-1 RAs and in the comparative control groups, the FDA cannot definitively rule out that a small risk may exist; therefore, the FDA is continuing to look into this issue.

Additional evaluations include a meta-analysis of clinical trials across all GLP-1 RA products and an analysis of postmarketing data in the Sentinel System. A meta-analysis is a large, combined analysis of findings from clinical trials. Sentinel is a very large data network that contains health insurance claims and patient health records that can be used to investigate safety questions about FDA-regulated products. The FDA will communicate final conclusions and recommendations after completion of the review or when there is more information to share.

BACKGROUND:

• GLP-1 RAs are a class of several medicines used to improve blood sugar (glucose) control and reduce the risk of heart disease in patients with type 2 diabetes. Some of these medicines are also used to help patients with obesity or overweight to lose weight.

RECOMMENDATIONS:

Patients

• You should not stop taking GLP-1 RAs without first consulting your health care professional, as stopping these medicines may worsen your condition.

• Talk to your health care professional if you have questions or concerns.

• Tell your health care professional if you experience new or worsening depression, suicidal thoughts, or any unusual changes in mood or behavior.

• Call or text 988 or go to the website at https://988lifeline.org/, which provides free support for people in distress 24 hours a day, 7 days a week.

Health Care Professionals

The current prescribing information for the GLP-1 RAs approved to treat patients with obesity or overweight contains information about the risk of suicidal thoughts and actions. This information is also included in the labels of other types of weight loss medicines and is based on reports of such events observed with a variety of older medicines used or tested for weight loss.

• Consistent with the prescribing information for these medications, health care professionals should monitor for and advise patients using GLP-1 RAs to report new or worsening depression, suicidal thoughts, or any unusual changes in mood or behavior.

• Health care professionals should consult the prescribing information when treating patients with these medications.

GLP-1 RAs are a class of several medicines (see list in Table 1) used to improve blood sugar (glucose) control and reduce the risk of heart disease in patients with type 2 diabetes. Some of these medicines are also used to help patients with obesity or overweight to lose weight. FDA approved the first GLP-1 RA in 2005, and there are now several in this class. GLP-1 RAs work by mimicking a hormone in the intestines called GLP-1 to stimulate the release of insulin and reduce blood glucose after eating a meal. These medicines also slow down food traveling through the digestive tract, which can help make someone feel full longer. GLP-1 receptors are also present in parts of the brain that regulate appetite.

Table 1. FDA-Approved GLP-1 RAs

**Tirzepatide is a dual gastric inhibitory polypeptide (GIP) receptor and GLP-1 RA.

Health care professionals, patients and consumers can sign up for email alerts about Drug Safety Communications on medicines or medical specialties of interest to you.

Related Information:

• Diabetes Medicines

• The FDA’s Drug Review Process: Ensuring Drugs Are Safe and Effective

• Think It Through: Managing the Benefits and Risks of Medicines

Health professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:

• Complete and submit the report online.
• Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on form, or submit by fax to 1-800-FDA-0178.

Source: FDA

Incretin Mimetic Drugs for Type 2 Diabetes: Early Communication - Reports of Possible Increased Risk of Pancreatitis and Pre-cancerous Findings of the Pancreas

ISSUE: FDA is evaluating unpublished new findings by a group of academic researchers that suggest an increased risk of pancreatitis and pre-cancerous cellular changes called pancreatic duct metaplasia in patients with type 2 diabetes treated with a class of drugs called incretin mimetics. These findings were based on examination of a small number of pancreatic tissue specimens taken from patients after they died from unspecified causes. FDA has asked the researchers to provide the methodology used to collect and study these specimens and to provide the tissue samples so the Agency can further investigate potential pancreatic toxicity associated with the incretin mimetics.

BACKGROUND: Drugs in the incretin mimetic class include exenatide (Byetta, Bydureon), liraglutide (Victoza), sitagliptin (Januvia, Janumet, Janumet XR, Juvisync), saxagliptin (Onglyza, Kombiglyze XR), alogliptin (Nesina, Kazano, Oseni), and linagliptin (Tradjenta, Jentadueto). These drugs work by mimicking the incretin hormones that the body usually produces naturally to stimulate the release of insulin in response to a meal. They are used along with diet and exercise to lower blood sugar in adults with type 2 diabetes.

RECOMMENDATIONS: FDA has not reached any new conclusions about safety risks with incretin mimetic drugs. This early communication is intended only to inform the public and health care professionals that the Agency intends to obtain and evaluate this new information. FDA will participate in the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and National Cancer Institute’s (NCI) Workshop on Pancreatitis-Diabetes-Pancreatic Cancer in June 2013 to gather and share additional information. FDA will communicate its final conclusions and recommendations when its review is complete or when the Agency has additional information to report. 

The Warnings and Precautions section of drug labels and patient Medication Guides for incretin mimetics contain warnings about the risk of acute pancreatitis. FDA has not previously communicated about the potential risk of pre-cancerous findings  of the pancreas with incretin mimetics. FDA has not concluded these drugs may cause or contribute to the development of pancreatic cancer.

At this time, patients should continue to take their medicine as directed until they talk to their health care professional, and health care professionals should continue to follow the prescribing recommendations in the drug labels.

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:

• Complete and submit the report Online: www.accessdata.fda.gov/scripts/medwatch/index.cfm
• Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178
   

[03/14/2013 - Drug Safety Communication - FDA]

Related Information:

[09/25/2009 - Drug Safety Information - FDA]

[08/18/2008 - Drug Safety Information - FDA]

Victoza (liraglutide [rDNA origin]) Injection: REMS - Risk of Thyroid C-cell Tumors, Acute Pancreatitis

ISSUE: Novo Nordisk reminded healthcare professionals of important safety information about Victoza (liraglutide [rDNA origin]) injection required in a Risk Evaluation and Mitigation Strategy (REMS). The letter is being sent because a recent assessment of healthcare providers showed that some primary care providers are not fully aware of the serious risks associated with the use of Victoza.

Liraglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. It is unknown whether Victoza causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as human relevance could not be ruled out by clinical or nonclinical studies. Additionally, in clinical trials studying Victoza, there were more cases of pancreatitis in patients treated with Victoza than in patients treated with comparators.

BACKGROUND: FDA may require a REMS for newly or already approved prescription drug product when FDA determines that a REMS is necessary to ensure the benefits of a drug outweigh the risks of the drug. Victoza is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

RECOMMENDATION: Patients with thyroid nodules noted on physical examination or neck imaging obtained for other reasons should be referred to an endocrinologist for further evaluation. Although routine monitoring of serum calcitonin is of uncertain value in patients treated with Victoza, if serum calcitonin is measured and found to be elevated, the patient should be referred to an endocrinologist for further evaluation.

After initiation of Victoza, and after dose increases, observe patients carefully for signs and symptoms of pancreatitis (including persistent severe abdominal pain, sometimes radiating to the back, and which may or may not be accompanied by vomiting).

Healthcare professionals and patients are encouraged to report adverse events, side effects, or product quality problems related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:

• Complete and submit the report Online: www.accessdata.fda.gov/scripts/medwatch/index.cfm
• Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178

[June 2011 - Dear Healthcare Professional Letter - Novo Nordisk]

[May 2011 - Prescribing Information - Novo Nordisk]