Bydureon BCise FDA Alerts

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.

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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]

Byetta (exenatide)

[UPDATED 08/18/2008] Since issuing Information for Healthcare Professionals in October 2007, FDA has received reports of 6 cases of hemorrhagic or necrotizing pancreatitis in patients taking Byetta. Byetta is a medicine given by subcutaneous injection to help treat adults with type 2 diabetes. Of the 6 cases of hemorrhagic or necrotizing pancreatitis, all patients required hospitalization, two patients died and four patients were recovering at time of reporting. Byetta was discontinued in all 6 cases. Byetta and other potentially suspect drugs should be promptly discontinued if pancreatitis is suspected. There are no signs or symptoms that distinguish acute hemorrhagic or necrotizing pancreatitis associated with Byetta from the less severe form of pancreatitis. If pancreatitis is confirmed, initiate appropriate treatment and carefully monitor the patient until recovery. Byetta should not be restarted. Consider antidiabetic therapies other than Byetta in patients with a history of pancreatitis.

[Posted 10/16/2007] FDA has reviewed 30 postmarketing reports of acute pancreatitis in patients taking Byetta (exenatide), a drug used to treat adults with type 2 diabetes. An association between Byetta and acute pancreatitis is suspected in some of these cases. Amylin Pharmaceuticals, Inc. has agreed to include information about acute pancreatitis in the PRECAUTIONS section of the product label.

Healthcare professionals should be alert to the signs and symptoms of acute pancreatitis and instruct patients taking Byetta to seek prompt medical care if they experience unexplained, persistent, severe abdominal pain which may or may not be accompanied by vomiting. If pancreatitis is suspected, Byetta should be discontinued. If pancreatitis is confirmed, Byetta should not be restarted unless an alternative etiology is identified.

[October 16, 2007 - Information for Healthcare Professionals - FDA]