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Final ICER Report Finds Empagliflozin More Cost Effective Than Oral Semaglutide for Type 2 Diabetes

Mary Caffrey
Oral semgalutide’s price, along with its potential for adverse events, caused ICER to give empagliflozin the edge in cost effectiveness as physicians and health plans evaluate which type 2 diabetes therapy should be given after metformin.
Oral semaglutide, a much-anticipated treatment for type 2 diabetes (T2D) that FDA approved in September as an alternative to injectables, is not as cost effective as the well-known oral therapy empagliflozin, according to a final report from the Institute for Clinical and Economic Review (ICER).

ICER’s evidence report, released Friday, comes as Novo Nordisk meets with payers to ensure access to the first glucagon-like peptide-1 (GLP-1) receptor agonist that patients can take as a daily pill. Friday’s report compares clinical trial and cost data for oral semaglutide, sold as Rybelsus by Novo Nordisk; liraglutide, another GLP-1 sold as Victoza by Novo Nordisk; empagliflozin, sold as Jardiance by Eli Lilly and Boehringer Ingelheim; and sitagliptin, sold by Merck as Januvia.

For years, leaders from Novo Nordisk have said that oral semaglutide would allow GLP-1 receptor agonists to reach T2D patients who should be on these powerful therapies but won’t try injectable drugs. The will reach the market alongside Novo Nordisk’s existing injectable GLP-1s, once-weekly semaglutide (Ozempic), and once-daily liraglutide.

But oral semgalutide’s price, along with its potential for adverse events, caused ICER to give empagliflozin the edge in cost-effectiveness, as physicians and health plans evaluate which T2D therapy should be given after metformin. The report largely confirms draft findings released just before FDA approval; as expected, Novo Nordisk has since set a price for oral semaglutide that is similar to the injectable version.

“SGLT2 inhibitors and GLP-1 receptor agonists have become increasingly important therapies for type 2 diabetes because they help with weight loss and reduce cardiovascular risk beyond that seen with other therapies,” David Rind, MD, ICER chief medical office, said in a statement. “Patients seeking to use a GLP-1 agonist but wishing to avoid injection have had no oral options until oral semaglutide, which appears to have efficacy similar to the injectable GLP-1s.”

“However, judging from the list price or oral semaglutide, its net price is likely to be much higher than that of competitor oral treatments, including the SGLT2 inhibitor empagliflozin that appears to have similar benefits with fewer common side effects.”

Different Mechanisms of Action

GLP-1 agonists work by copying functions of naturally occurring hormones, incretins, that allow the body to lower blood sugar after a meal. The American Diabetes Association now recommends that physician prescribe them for patients who cannot achieve glycemic control before moving to insulin therapy, because they help patients lose weight. But they can cause gastrointestinal side effects and require titration until patients can tolerate an effective dose. In its report, ICER said, “A considerable portion of patients discontinued oral semaglutide due to adverse events, specifically gastrointestinal events.”

Empagliflozin, by contrast, is among the class of sodium glucose co-transporter 2 (SGLT2) inhibitors, which work by expelling excess glucose through the urine and have been shown to prevent heart failure and renal decline. The most common side effects with SGLT2 inhibitors are genitourinary tract infections while patients are adjusting to the drug. Empagliflozin and liraglutide were the preferred drugs in their respective classes in the 2018 American College of Cardiology Expert Consensus Decision Pathway for patients with T2D and atherosclerotic cardiovascular disease.

ICER Reviews Clinical Benefits

ICER’s report states, “For the comparison between oral semaglutide and empagliflozin, semaglutide lowers [glycated hemoglobin] and controls blood glucose better than empagliflozin with similar effects on weight.” This was based on findings from the EMPA-REG OUTCOME trial for empagliflozin and the PIONEER trial program for oral semaglutide, including a head-to-head comparison of oral semaglutide and empagliflozin in PIONEER 2. While both oral and injectable semaglutide reduced cardiovascular events—the FDA is reviewing a request for CV indications—ICER found that the low number of events for oral semaglutide was not statistically significant. Empagliflozin, by contrast, made waves in 2015 when it was the first T2D therapy to demonstrate a clear cardiovascular benefit.

Beyond its discussion of gastrointestinal events, ICER also found that “Semaglutide may increase rates of retinopathy. In the head-to-head PIONEER trials, the rate of adverse events with oral semaglutide 14 mg ranged from 70.5% to 80% compared to 69.2% to 83.3% with the comparator therapies.”

In its summary comparing the clinical benefits of oral semaglutide and empagliflozin, ICER’s review states: “Given these competing risks and benefits, overall we have low certainty in the net health benefit of oral semaglutide compared with empagliflozin and judge the evidence insufficient.”

Empagliflozin Clear Winner on Cost

ICER relied on data from SSR Health LLC for information on list prices, discounts, and net costs for oral semaglutide, empagliflozin, liraglutide, and sitagliptin, a dipeptidyl peptidase-4 inhibitor. The information showed that oral semaglutide had a list price of $772 for 30 days, which put its monthly cost in line with other GLP-1s, but made it more expensive than other oral therapies, including empagliflozin. The ICER report found the net price for oral semaglutide per 30 days was $501, compared with a list price/net price of $492/$174 for empagliflozin.

Published reports from Fierce Pharma suggest that Novo Nordisk faced a quandary, because sales of injectable semaglutide have been strong, and pricing the oral formulation too low would undercut their other GLP-1 products.

In a conference call on its third-quarter earnings report Friday, one analyst asked if the manufacturer expected patients to be required to take an SGLT2 inhibitor before being approved for oral semaglutide. President and CEO Lars Fruergard Jorgensen said, “We cannot comment on the level of access now and also whether there’ll be step edits. Clearly, that’s not our objective. We are still early in the process...of negotiating this access.”

The ICER Evidence Reivew will be discussed November 14, 2019, by the New England Comparative Effectiveness Public Advisory Council.

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