Newer Options for SGLT2 Inhibitors in the United States

Millions of patients living with cardiovascular, kidney, and metabolic syndrome would benefit from treatment with sodium-glucose cotransporter-2 inhibitors (SGLT2i), yet their uptake in eligible populations remains poor. One study from 2022 showed that only 8% of patients with kidney diseases and diabetes received an SGLT2i (1); the combination of chronic kidney disease (CKD) and diabetes is a class 1A indication for SGLT2i therapy in the 2023 KDIGO guidelines draft (2). Drug cost is one barrier to patient access to this lifesaving class of medications. Three new entries in the SGLT2i market offer additional options for patients and their nephrologists.

The US Food and Drug Administration approved sotagliflozin in May 2023. Sotagliflozin is an inhibitor of SGLT1 and -2 combined. While SGLT2 is present in the nephron, SGLT1 receptors are in the gut. Sotagliflozin was approved for the treatment of patients with heart failure, CKD, and/or diabetes with the indication of preventing and reducing heart failure hospitalizations and cardiovascular death. The approval was based on data from the SOLOIST-WHF (NCT03521934) and SCORED (NCT03315143) trials, and it covers heart failure with both reduced and preserved ejection fractions (3). Sotagliflozin will be sold under the brand name Inpefa and is expected to be available mid-2024.

The SGLT2i bexagliflozin was approved in January 2023 as adjunctive therapy to lower blood glucose in patients with type 2 diabetes. Patients with an estimated glomerular filtration rate less than 30 are excluded on the label (4). Bexagliflozin (brand name Brenzavvy) was not expected to have much success as a late entrant into the field, especially since established SGLT2i, including dapagliflozin (Farxiga), canagliflozin (Invokana), and empagliflozin (Jardiance), have additional cardiovascular and kidney-labeled indications. However, in a novel marketing approach, bexagliflozin is available exclusively through Cost Plus Drugs at a cash price of approximately $50 per month (5). There are no required patient assistance programs or other qualifying steps to access the medication (Table 1). Prescribing physicians should exercise their best clinical judgment to determine if the evidence for a class effect of the SGLT2i is enough to warrant off-label use of bexagliflozin to provide benefit among patients with cardiovascular and kidney diseases.

Table 1

Manufacturer savings available for various SGLT2 inhibitors

View Table

AstraZeneca's Farxiga (dapagliflozin) does not go off patent until 2025, and in 2021, AstraZeneca successfully defended its patent against a challenge from a manufacturer of generic medications (6). However, generic dapagliflozin is now available in the United States. In a marketing strategy familiar to Costco shoppers, who purchase brand name products sold under the Kirkland label at a significant discount, AstraZeneca has licensed Prasco to sell dapagliflozin as an authorized generic. The medication is manufactured in the same facility as the branded product and is identical other than the packaging (7). There is the potential for savings to be passed on to the consumer, although the savings may also be captured by pharmacy benefit managers and the pharmacies.

These three new options in this important drug class may allow more patients to benefit.

These three new options in this important drug class may allow more patients to benefit. With such low prescribing rates for eligible patients, however, it seems likely that the larger barrier is doctors’ inertia in updating their practice patterns. More education is needed to encourage the use of SGLT2i in accordance with the new standard of care.