Albiglutide (Tanzeum): the withdrawn weekly GLP-1

Albiglutide is the cautionary tale of the class. It arrived in 2014 as a once-weekly drug, five months before dulaglutide, with a pen that needed reconstituting from powder and a potency that trailed the daily competitor it was compared against. It is listed as discontinued in Drugs@FDA, and its cardiovascular benefit was published after it had gone.

Mechanism and receptor profile

The Tanzeum label describes it as an agonist of the GLP-1 receptor that augments glucose-dependent insulin secretion and slows gastric emptying. The molecule is a fusion of GLP-1 sequences with human albumin; the albumin carries it for a week, the same idea as dulaglutide's antibody fragment and a different one from semaglutide's fatty-acid albumin binding. The label notes that carcinogenicity could not be assessed in rodents because albiglutide is not pharmacologically active in them, so its boxed warning is inherited from the class rather than from its own animal data, the same situation later faced by orforglipron.

FDA approval

One approval: 15 April 2014, BLA 125431, new molecular entity, as an adjunct to diet and exercise for glycemic control in adults with type 2 diabetes. The label carried a limitation of use, unusual for the class, stating it was not recommended as first-line therapy because of the uncertain relevance of the rodent C-cell tumor findings. Drugs@FDA lists the marketing status as discontinued and the final label revision as supplement 20, dated 20 December 2017.

Dosing as the label stated it

30 mg once weekly by subcutaneous injection in the abdomen, thigh or upper arm, at any time of day without regard to meals; may be increased to 50 mg weekly if the glycemic response is inadequate. The lyophilised powder was reconstituted inside the pen before use. Missed doses were to be taken within 3 days; the injection day could be changed if the last dose was 4 or more days earlier.

Pivotal trials and their numbers

Harmony Outcomes ended once the target number of events had accrued; the abstract records that patients were told to discontinue study treatment in November 2017, the month before the last label revision.

Adverse reactions from the label

Two things stand out against the rest of the class. Nausea was barely above placebo, which the HbA1c results suggest came at the cost of potency. And injection-site reactions at 10.5% were five times placebo.

Boxed warning

The class thyroid C-cell tumor warning, with the label's own admission that carcinogenicity could not be assessed in rodents. Contraindicated with a personal or family history of medullary thyroid carcinoma or MEN 2. Other warnings: pancreatitis, hypoglycemia with insulin or secretagogues, hypersensitivity, acute kidney injury.

Status and manufacturer

GlaxoSmithKline. Discontinued per Drugs@FDA. The approval remains on the record, so albiglutide is "approved but not marketed" rather than "unapproved", a distinction the approved, investigational and compounded guide explains.

Where next

Dulaglutide, approved five months later with a ready-to-use pen and a stronger HbA1c result, is the product that took the market albiglutide was built for.