乌鸦传媒

While the GLP-1 receptor agonist albiglutide (Tanzeum) was withdrawn from the market in 2017, it has now proven to cut cardiovascular events in type 2 diabetes.

In the Harmony Outcomes trial, a weekly injection of albiglutide significantly reduced the primary composite of stroke, myocardial infarction (MI), and cardiovascular (CV) death compared with placebo (7% vs 9% at a median 1.5 years, HR 0.78, 95% CI 0.68-0.90, P=0.0006 for superiority) among adults with type 2 diabetes with established cardiovascular disease.

The benefit with the drug added to standard care regimens was driven by a reduction in fatal or nonfatal MI (HR 0.75, 95% CI 0.61-0.90), reported Stefano Del Prato, MD, of the University of Pisa in Italy, at the European Association for the Study of Diabetes (EASD) in Berlin and published simultaneously online in .

The other endpoints in the composite primary outcomes were not significant:

• CV death: HR 0.93 (95% CI 0.73-1.19, P=0.578)
• Fatal or nonfatal stroke: HR 0.86 (95% CI 0.66-1.14, P=0.3000)

But the researchers suggested that a longer follow-up period may have lent itself to a significant reduction in CV death, as was seen with fellow GLP-1 drug liraglutide (Victoza) in the 3.8-year long LEADER trial.

Del Prato recommended that this class of agents should therefore be a component to a comprehensive diabetes management plan aimed at reducing major adverse cardiovascular event risk.

This was echoed by Sanjay Kaul, MD, of Cedars-Sinai Medical Center in Los Angeles, who was not involved with the study. He noted that these findings were also similar to what was seen with the GLP-1 receptor agonist semaglutide (Ozempic) in SUSTAIN-6 -- even though Harmony Outcomes had a shorter follow-up period.

"A 2% absolute and 22% relative risk reduction in the primary composite endpoint of three-point MACE that was driven by significant reduction in nonfatal MI with CV death and nonfatal stroke leaning in favor of albiglutide on the background of optimal cardioprotective therapy is quite impressive," he told 乌鸦传媒.

This trial took place across 610 international centers and recruited adults over the age of 40 with type 2 diabetes with an HbA1c over 7% and established coronary, cerebrovascular, or peripheral arterial circulation disease between 2015 and 2016. The 4,731 patients, randomized in a 1:1 ratio, received albiglutide, while 4,732 patients received placebo. The starting dose of albiglutide was 30 mg and was later increased up to 50 mg depending upon patient tolerability and glycemic goal.

Not surprisingly, patients who received albiglutide also saw a significant drop in their HbA1c (difference from placebo at 16 months -0.52%, -0.58 to -0.45) and body weight (-0.83 kg, -1.06 to -0.60) when compared with placebo. There was also a slight decrease in systolic blood pressure seen with albiglutide treatment over 16 months of treatment (-0.67 mm Hg, -1.40 to 0.06).

Although the specific underlying mechanisms accounting for the cardiovascular benefit with albiglutide is still uncertain, Del Prato suggested that it is more than likely that this benefit wasn't solely due to the glucose-lowering effect or the benefit with body weight and blood pressure.

"What can be hypothesized is an anti-atherogenic effect and/or a direct effect on the cardiovascular system. The former is in line with the time required for the risk curve to separate and the second with a number of mechanisms observed in pre-clinical studies," he suggested.

Albiglutide treatment was also generally safe without any differences in serious adverse events between the two groups, including for acute pancreatitis (10 in albiglutide versus seven placebo), pancreatic cancer (six versus five), and for medullary thyroid carcinoma (0 versus 0).

However, following FDA approval back in 2014, maker GlaxoSmithKline later pulled albiglutide from the market in 2017 due to poor sales following the addition of a warning on the label for risk of anaphylactic reactions -- adding to the previous boxed warning for thyroid c-cell tumors.

Kaul emphasized that the robustness of this data is sufficient to meet the FDA's criteria for efficacy, but noted that a longer follow-up period would have been preferred in terms of safety concerns. "Whether the sponsor would be incentivized by these data to resuscitate this drug remains the $64,000 question."

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