Type 2 diabetes mellitus (T2DM) makes up 90% to 95% of all diabetes diagnoses and affects approximately 26 million adults in the United States.1,2 The 2016 American Diabetes Association's Standards of Medical Care in Diabetes supports the use of metformin hydrochloride as initial monotherapy in the treatment of T2DM; however, most patients eventually require multiple antidiabetic medications to manage their disease.3

The guidelines state that any available class of medications, including glucagon-like peptide-1 (GLP-1) receptor agonists, may be added to metformin as a second-line option or used in place of metformin in patients with a contraindication or intolerance to metformin.3 On April 15, 2014, the FDA approved the GLP-1 receptor agonist albiglutide (Tanzeum) for the treatment of T2DM.4

Albiglutide was studied in the HARMONY clinical trial series, which consisted of eight individual phase-III clinical trials. It was studied in patients with kidney impairment in one trial, as add-on therapy in six of the trials, and as monotherapy in one trial. Albiglutide was compared with placebo, oral antidiabetic medications, insulin, and liraglutide throughout the HARMONY clinical trial series.5 Albiglutide, added to pioglitazone, lowered hemoglobin A1c (HbA1c) significantly more than placebo.6

Albiglutide was deemed to be noninferior to basal insulin and produced similar HbA1c lowering to insulin glargine.7 Additionally, subjects on albiglutide experienced statistically significant weight loss compared with the weight gain seen with insulin glargine.7 Albiglutide did not meet noninferiority criteria for HbA1c lowering when compared with pioglitazone; however, a statistically significant weight loss was seen in the albiglutide treatment group compared with the pioglitazone treatment group.8

Albiglutide has not been studied head-to-head against the other currently available, once-weekly GLP-1 receptor agonists, dulaglutide and extended-release exenatide; however, it was studied against the once-daily GLP-1 receptor agonist liraglutide during phase-III trials.5 In the HARMONY 7 trial, albiglutide did not meet noninferiority criteria for HbA1c lowering when compared with liraglutide.9 Albiglutide resulted in an approximate 0.8% reduction in HbA1c compared with a 1% reduction in HbA1c in the liraglutide treatment group.9,10 Greater reductions in fasting plasma glucose and weight were also observed in the liraglutide treatment group with a statistically significant p-value of less than 0.005 for both secondary outcomes in favor of liraglutide.9,10

Indication

Albiglutide is approved for use in adults with T2DM to increase glycemic control when used in addition to lifestyle modifications (diet and exercise).10

Mechanism of action

Albiglutide binds to GLP-1 receptors in the body, causing an increased release of glucose-dependent insulin from the beta cells of the pancreas and a decrease in gastric emptying.10

Dosing and administration

Albiglutide is initiated at a dose of 30 mg once weekly with an optional titration to 50 mg once weekly (if needed for additional glycemic lowering). The product is supplied as an injectable pen device given subcutaneously in the abdomen, thigh, or upper arm. The weekly dose of albiglutide should be administered on the same day each week with or without food. Patients are able to change the day of administration pending the new day is at least 4 days after the last administered dose.10

The pen device contains a lyophilized powder and diluent, which are reconstituted prior to administration using the instructions provided with the medication. Once reconstituted, the pen must be used within 8 hours as long as the supplied needle has not been attached. Once the needle is attached and primed, the dose must be administered immediately. Albiglutide may be injected in the same body region as insulin as long as the injections are not given adjacently to one another.10

Contraindications

Albiglutide should not be prescribed for patients with a personal or family history of medullary thyroid carcinoma or patients with multiple endocrine neoplasia syndrome type 2. The development of thyroid c-cell tumors was seen in animal studies with GLP-1 receptor agonists.10 A Black Box Warning exists for all GLP-1 receptor agonists restricting their use in these patient populations. This product should also be avoided in patients with a history of a serious hypersensitivity reaction to albiglutide or any of its components. Hypersensitivity reactions to albiglutide were observed in clinical trials.10

Warning and precautions

Episodes of acute pancreatitis were observed in the clinical trials of albiglutide. Patients on albiglutide should be monitored for signs and symptoms of pancreatitis, such as severe, radiating abdominal pain. Albiglutide should be discontinued in patients with suspected pancreatitis, and the drug should not be reinitiated in patients with confirmed pancreatitis. Patients with a history of pancreatitis should be considered for other antidiabetic medications.10

Using albiglutide with insulin or insulin secretagogues (such as sulfonylureas) increases the risk of hypoglycemia. Patients on insulin or insulin secretagogues may require reductions in the dose of these agents when used in combination with albiglutide.10

Acute kidney failure and further decline of chronic kidney disease has been observed in postmarketing surveillance of GLP-1 receptor agonists. Clinical trials of albiglutide use in patients with kidney dysfunction reported an increase in the frequency of gastrointestinal reactions as kidney function decreased. Practitioners should use caution when starting or titrating albiglutide in patients with kidney dysfunction.10 Similar to other antidiabetic medications, there was no decisive evidence of reduction in cardiovascular risk with albiglutide use.10

Adverse reactions

The most common adverse reactions observed in placebo and active controlled clinical trials of albiglutide were gastrointestinal adverse reactions-specifically nausea-and injection site reactions.10 These reactions led to participant withdrawal in multiple clinical trials.7,8,10 Other adverse reactions seen in less than 2% of the albiglutide treatment arms included pneumonia, atrial fibrillation, appendicitis, liver enzyme abnormalities, and heart rate increase.10

Drug interactions

Albiglutide delays gastric emptying, and therefore may affect the absorption of concurrently administered oral medications. Although clinically significant alterations in the absorption of oral medications were not observed in pharmacologic studies of albiglutide, caution should still be used when oral medications are administered concomitantly with albiglutide.10

Pharmacokinetics

A single 30 mg dose of albiglutide reaches peak plasma concentrations in 3 to 5 days. Steady-state concentrations are achieved after 4 to 5 weeks of once-weekly dosing. Albiglutide has a clearance of 67 mL/h and a half-life of 5 days, which makes it appropriate for once-weekly dosing.10 The drug is metabolized into small peptides and amino acids in the vascular endothelium by ubiquitous proteolytic enzymes. The effect of hepatic dysfunction on albiglutide has not been studied.10

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