SGLT2 Inhibitors, GLP-1 RAs Not Cost-Effective as First-Line T2D Agents

Although using newer classes of diabetes drugs as first-line therapy can boost life expectancy, this strategy can be quite pricey, according to a cost-effectiveness study.

Compared with traditional first-line metformin, first-line SGLT2 inhibitors cost $43,000 more over a lifetime, and first-line GLP-1 receptor agonists cost $49,000 more, reported Neda Laiteerapong, MD, MS, of the University of Chicago, and colleagues.

Ultimately, no first-line strategy aside from metformin fell below the willingness-to-pay threshold of $150,000 per quality-adjusted life-year (QALY) -- the criteria for being "cost-effective," the group noted in the Annals of Internal Medicine.

First-line SLGT2 inhibitors had an incremental cost-effectiveness ratio (ICER) of $478,000 per QALY compared with metformin, while oral GLP-1 receptor agonists had an ICER of $823,000 per QALY.

"Based on a willingness-to-pay threshold of under $150,000 per QALY, SGLT2 inhibitors and oral GLP-1 receptors would become cost-effective at $1,800 per year ($5 per day) and $2,100 per year ($6 per day), respectively, requiring cost reductions of at least 70% for SGLT2 inhibitors and at least 90% for oral GLP-1 receptor agonists," Laiteerapong and team wrote.

Of note, the researchers projected that first-line SGLT2 inhibitors and GLP-1 receptor agonists would slightly increase overall life expectancy, by 3 and 3.4 months, respectively. Furthermore, SGLT2 inhibitors increased quality-adjusted life expectancy (QALE) by 33 days compared with metformin, but GLP-1 receptor agonists deceased QALE by 22 days, in part due to injection disutility.

The newer agents also offered other benefits, particularly when it came to cutting the rate of certain complications.

Stroke complications, which accounted for 10% to 14% of the total costs for each treatment strategy (around $20,000), were the most common with metformin. All lifetime macrovascular complications were highest in the metformin group and lowest in the GLP-1 receptor agonist group:

• Heart failure: 14.2% with metformin vs 13.2% with SGLT2 inhibitors vs 13.1% with GLP-1 receptor agonists
• Ischemic heart disease: 18.8% vs 17.3% vs 17.2%
• Myocardial infarction: 27.0% vs 26.0% vs 25.5%
• Stroke: 17.2% vs 16.3% vs 16.2%

On the other hand, lifetime rates of microvascular complications, including amputation, blindness, and end-stage renal disease, were relatively similar across all three first-line strategies, as were estimated lifetime rates of foot ulcers (2.9% in all groups).

"While [the newer agents] do change cardiovascular risk factors and outcomes, I didn't think the costs would justify the benefits," Laiteerapong told MedPage Today.

"I was very excited about these newer classes of diabetes drugs because of their potential to change cardiovascular outcomes in people with diabetes, but simultaneously I was concerned about their costs," she added. "I thought that the clinical leaders would be very excited for the benefits of these drugs and start to push for these drugs ahead of metformin and wanted to understand the cost-effectiveness of this potential decision."

Laiteerapong said that clinicians should advocate for lower costs for drugs that are highly effective, especially to reduce health disparities due to inaccessibility to these medications.

This notion is backed by several recent studies, which have found low uptake of SGLT2 inhibitors and GLP-1 receptor agonists across racial minorities, women, and patients with lower incomes.

For the current study, Laiteerapong's group used data on adults with self-reported type 2 diabetes in the National Health and Nutrition Examination Surveys from 2013 to 2016. They used an individual patient-level Monte Carlo-based Markov model to simulate the lifetime incidence, prevalence, mortality, and costs associated with a U.S.-representative population with type 2 diabetes not being treated with diabetic medications. All three medications were administered as a first-line therapeutic if and when HbA1c was at least 7.0%, according to American Diabetes Association/European Association for the Study of Diabetes guidelines.

Estimated costs for each of the three medications were calculated on lifetime medication use, complications, hospital utilization, and self-monitoring like testing and supplies.

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