Comments from the Authors
The Food and Drug Administration (FDA) issued a reminder through the MedWatch program to providers on June 13, 2011 that highlighted the risk of thyroid carcinoma and acute pancreatitis with the use of liraglutide (Victoza). This was prompted by a letter from Novo Nordisk, the maker of liraglutide, after an assessment revealed that not all primary care providers were aware of these serious conditions.
In the June 2011 issue of the Southern Medical Journal, we reviewed the published data with liraglutide and also discussed the safety of the use of the medication.1 Although known to cause dose-dependent and treatment duration–dependent thyroid C-cell tumors in male and female rats, human risk has not been quantified in clinical studies.2 As highlighted in our article, there was an increased risk of acute pancreatitis in users of liraglutide compared with those treated with other medications.3–8 The drug is contraindicated in patients with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2. The FDA urged providers who evaluate a patient with thyroid nodules on liraglutide to refer the patient to an endocrinologist. The FDA also recommended that providers be aware of the signs and symptoms of pancreatitis at initiation and at dosage titration. Liraglutide should be discontinued in a patient with suspected pancreatitis until the diagnosis can be ruled out.
Novo Nordisk initiated a Risk Evaluation Management Strategy (REMS) when the drug was approved in 2010 to create a cancer registry to identify patients with thyroid carcinoma who were taking the medication. In May, the company updated the REMS to include a Dear Health Care Professional (DHCP) letter to be mailed out in June that addressed the risk. A direct mail letter will be sent once per year 6 months after the DHCP letter is sent that reiterates safety information. The company will also be required to address its safety efforts with liraglutide to the FDA for the next 6 years.
Until further safety data are available, use of liraglutide should be deferred as second- or third-line therapy for the treatment of type 2 diabetes mellitus. Providers should continue to be diligent in the evaluation of potential complications associated with liraglutide. Healthcare professionals and patients should report adverse events with liraglutide to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program.
M. Shawn McFarland, PharmD
Meghan Brock, PharmD
Casey Ryals, PharmD
References
1. McFarland M, Brock M, Ryals C. Place in therapy for liraglutide and saxagliptin for type 2 diabetes. South Med J 2011;104:426–439.
2. Parks M, Rosenbaugh C. Weighing the risks and benefits of liraglutide—the FDA’s review of a new antidiabetic therapy. N Engl J Med 2010;362:774–777.
3. Marre M, Shaw J, Brandle M, et al. Liraglutide, a once-daily human GLP-1 analogue, added to a sulfonylurea over 26 weeks produces greater improvements in glycemic and weight control compared with adding rosiglitazone or placebo in subjects with type 2 diabetes (LEAD-1 SU).
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4. Nauck M, Frid A, Hermansen K, et al. Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes (the LEAD-2 Study). Diabetes Care 2009;32:84–90.
5. Garber A, Henry R, Ratner R, et al. Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomized, 52-week, phase III, double-blind, parallel-treatment trial. Lancet 2009;373:473–481.
6. Zinman B, Gerich J, Buse JB, et al. Efficacy and safety of the human glucagon-like peptide-1 analog liraglutide in combination with metformin and thiazolidinedione in patients with type 2 diabetes (LEAD-4 Met-TZD). Diabetes Care 2009;32:1224–1230.
7. Russell-Jones D, Vaag A, Schmitz O, et al. Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus: a randomised controlled trial (LEAD-5 Met+ SU). Diabetologia 2009;52:2046–2055.
8. Buse JB, Rosenstock J, Sesti G, et al. Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomized, parallelgroup, multinational, open-label trial (LEAD-6). Lancet 2009;374:39–47.