New once-weekly treatment for type 2 DM

Kathryn WheelerOn April 15, 2014, albiglutide (Tanzeum; GlaxoSmithKline) was approved for improvement of glycemic control in patients with type II diabetes in addition to diet and exercise. It is the newest glucagon-like peptide-1 receptor agonist (GLP-1) approved for once-weekly dosing. GLP-1 agonists stimulate glucose-dependent insulin release from the pancreas, slow gastric emptying, inhibit glucagon release, and promote satiety.

As with all GLP-1 agonists, albiglutide has been associated with an increased risk of pancreatitis and possibly thyroid tumors. It has a boxed warning and a REMS program to ensure that the benefits of use outweigh the associated risks and that patients are informed of these risks. Information regarding the albiglutide REMS program can be found at www.tanzeumrems.com.

Efficacy

FDA approval of albiglutide was based on a series of eight trials, in which more than 2,000 participants with type 2 diabetes were treated with albiglutide. Albiglutide was investigated as both a monotherapy to be used in conjunction with diet and exercise, and as a combination therapy added to metformin; a sulfonylurea plus metformin; a thiazolidinedione with and without metformin; insulin glargine monotherapy; and insulin glargine plus other antidiabetic medications.

These studies compared the efficacy of albuglutide to placebo or to an active therapy (sulfonylurea, dipeptidylpeptidase IV [DPP-IV] inhibitor, thiazolidinedione, and both rapid and long-acting insulins (lispro and glargine). Overall, albiglutde demonstrated a significant reduction in hemoglobin A1c without a significant participant weight reduction.

 A noninferiority study compared albiglutide to liraglutide, a once-daily GLP-1 agonist. In this open-label trial, participants taking liraglutide achieved greater reductions in A1c. However, participants receiving albiglutide experienced fewer gastrointestinal adverse effects and injection site reactions.

Safety

Adverse reactions occurring more frequently with albiglutide compared to placebo include: hypoglycemia, infection (upper respiratory infection, influenza, sinusitis), cough, back pain, injection site reactions, and elevations in liver enzymes. Mild-to-moderate gastrointestinal reactions (nausea, vomiting, diarrhea, reflux, and dyspepsia) were also more common with albuglutide use and occurred more commonly in association with renal dysfunction.

Post-marketing reports indicate GLP-1 agonist therapy may be associated with acute renal failure or worsening of chronic kidney disease, which may lead to dialysis. Dehydration and adverse gastrointestinal reactions have been associated with many of these reports. Atrial fibrillation/flutter occurred more frequently among albiglutide users, most commonly among male participants with cardiac or renal disease. There are no recommendations as to the use of albiglutide in these patients.

 Acute pancreatitis, a rare but serious adverse reaction associated with all GLP-1 agonists, occurred in trials among albiglutide users. Patients taking albiglutide should be instructed to contact their physicians should they experience severe, persistent abdominal pain, which may be accompanied by vomiting.

Patients must also be counseled regarding the risk and symptoms of medullary thyroid carcinoma (MTC). Patients taking albuglutide experiencing persistent hoarseness, difficulty speaking or breathing, or a mass in their neck should contact their physicians. Any patient experiencing pancreatitis or MTC should permanently discontinue albiglutide.

FDA mandated post-marketing studies of use in pediatrics and cardiovascular outcomes in patients with underlying cardiovascular disease; it also called for a 15-year MTC case registry.

Dosage

The recommended starting dose of albiglutide is 30 mg once weekly, delivered as a subcutaneous injection in the abdomen, thigh, or upper arm. The dosage may be increased to 50 mg as needed for improved glycemic control. Albiglutide is administered without regard to meals, but should be administered on the same day each week. No dose adjustment is necessary for any degree of renal impairment. However, caution is recommended due to the increased frequency and severity of gastrointestinal adverse reactions. The medication is available as a single-dose injection pen, which must be reconstituted prior to use.

Albiglutide should not be mixed with insulins or other injectable medications. To avoid hypoglycemia, the dose of concomitant antidiabetic medications or insulin may require adjusting when a patient starts or increases the dose of albiglutide. Pregnancy category C albiglutide therapy should provide enough benefit to justify the risk of use during pregnancy. The manufacturer recommends discontinuing the drug at least a month before a planned pregnancy is initiated. Albiglutide probably crosses into breast milk. Therefore, a decision to discontinue either breastfeeding or albiglutide use is required.