Empagliflozin Beats Pair of DPP-4s in Cost-Effectiveness for Patients With Type 2 Diabetes, CVD

Empagliflozin, the sodium glucose co-transporter 2 (SGLT2) inhibitor sold as Jardiance, was more effective for patients with type 2 diabetes (T2D) and established cardiovascular disease than either of 2 well-known drugs from a competitor class, when used with standard of care, according to an analysis just published in Diabetes Therapy.

Researchers used the IQVIA Core Diabetes Model (CDM) to evaluate empagliflozin against sitagliptin (Januvia) and saxagliptin (Onglyza), both from the dipeptidyl peptidase-4 (DPP-4) inhibitor class. Drugs in this second class have generally been found to not affect cardiovascular outcomes, although saxagliptin was found to increase the risk of hospitalization for heart failure. By contrast, the SGLT2 inhibitor class has been found to have cardiovascular benefits, with empagliflozin becoming the first glucose-lowering therapy to demonstrate a reduction in major cardiovascular events. In June, the FDA has granted fast track designation to empagliflozin for prevention of heart failure based on early data from dedicated outcomes studies, the EMPEROR trials.

The IQVIA CDM was calibrated to reflect results from the cardiovascular outcomes trials (CVOTs) required by a 2008 FDA guidance: the EMPA-REG OUTCOME trial for empagliflozin, the TECOS trial for sitagliptin, and the SAVOR-TIMI 53 trial for saxagliptin. According to the authors, 3-year observed events for empagliflozin plus standard of care were compared with results for each of the 2 DPP-4 inhibitors plus standard of care. The analysis was conducted based on the perspective of the UK National Health Service, and cost and quality data were taken from that health system. The time horizon for the analysis was 50 years.

The authors recognized that a variety of glucose-lowering therapies were being used at the time of study drug initiation in the various trials—from metformin, to sulfonylureas, to insulin—and that with a long time horizon, it made sense to calculate a treatment switch once a glycated hemoglobin (A1C) of 8.5% was reached. Basal-bolus insulin was the most obvious escalation therapy, with calculations based on high-dose mealtime insulin and a high dose of insulin glargine.

Results. Adding empagliflozin offered additional life years—0.766 compared with sitagliptin and 1.053 compared with saxagliptin (all with standards of care). Quality-adjusted life years were also greater for empagliflozin at 6.408, compared with 5.917 for sitagliptin and 5.704 for saxagliptin; this came at an additional cost of £3174 (US $3987) and £2730 GBP (US $3429), respectively. Authors reported that the incremental cost-effectiveness ratios were of empagliflozin were £6464 (US $8124)/QALY for sitagliptin and £3878 (US $4873)/QALY for saxagliptin. Both amounts were well below the willingness to pay threshold of £20,000 (US $25,128/QALY established by the National Institute for Health and Care Excellence (NICE).

Separately, authors reported data that show patients taking empagliflozin had less risk of macrovascular and microvascular events, less risk of eye disease, reduced risk of neuropathy, and reduced risk of hypoglycemia. They report on the survival paradox: the short-term benefit that empagliflozin offers in reducing the risk of death due to cardiovascular disease or reducing the risk of heart failure, heart attack, eye disease, or kidney failure, they write, is “partly offset by the extended life expectancy and prolonged time exposure to diabetes complications.”

Notably, the authors say, 6 other studies based on data from the United Kingdom, Canada, and the United States have shown that empagliflozin is cost-effective in patients with T2D and cardiovascular disease.

Reference

Ramos M, Foos V, Ustyugova A, Hau N, Gandhi P, Lamotte M. Cost-effectiveness analysis of empagliflozin in comparison to sitagliptin and saxagliptin based on cardiovascular outcome trials in patients with type 2 diabetes and established cardiovascular disease [published October 10, 2019]. Diabetes Ther. 2019; doi: 10.1007/s13300-019-00701-3.