General Information

Inpefa (sotagliflozin) is a sodium-glucose cotransporter 2 (SGLT2) inhibitor.

Inpefa is specifically indicated to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in adults with:

• heart failure or
• type 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors

Inpefa is supplied as tablets for oral administration.

Dosing/Administration

• Assess volume status and, if necessary, correct volume depletion prior to initiation of Inpefa.
• Assess renal function prior to initiation of Inpefa and then as clinically indicated.
•  For patients with decompensated heart failure, dosing may begin as soon as the patient is hemodynamically stable, including during hospitalization or urgent outpatient treatment or immediately upon discharge.  

The recommended starting dose of Inpefa is 200 mg orally once daily not more than one hour before the first meal of the day. Up-titrate after at least 2 weeks to 400 mg orally once daily as tolerated. Down-titrate to 200 mg as necessary. Swallow tablets whole. Do not cut, crush, or chew tablets. If a dose of Inpefa is missed by more than 6 hours, take the next dose as prescribed the next day.

Mechanism of Action

Inpefa (sotagliflozin) is an inhibitor of SGLT2 and SGLT1. Inhibiting SGLT2 reduces renal reabsorption of glucose and sodium which may influence several physiological functions such as lowering both pre-and afterload of the heart and downregulating sympathetic activity. Inhibiting SGLT1 reduces intestinal absorption of glucose and sodium which likely contributes to diarrhea. The mechanism for sotagliflozin’s cardiovascular benefits has not been established.

Side Effects

Adverse effects associated with the use of Inpefa may include, but are not limited to, the following:

• urinary tract infection
• volume depletion
• diarrhea
• hypoglycemia

Clinical Trial Results

FDA approval of Inpefa was based on two randomized, double-blind, placebo-controlled Phase 3 cardiovascular outcomes studies in patients with heart failure or at risk of heart failure. Together, SOLOIST-WHF (Worsening Heart Failure) and SCORED enrolled almost 12,000 patients. Results from SOLOIST-WHF showed that Inpefa significantly reduced risk of the composite of hospitalizations for heart failure, urgent visits for heart failure, and cardiovascular death by 33% compared to placebo in patients who had been recently hospitalized for worsening heart failure.

For pooled patient data across both trials: compared with placebo, overall results found Inpefa resulted in significant reductions over a median period of nine to 16 months in the risk of death due to cardiovascular causes and hospitalization or an urgent visit for HF, irrespective of ejection fraction at study entry, across both patient groups. Among those patients with an ejection fraction of 40% or less, Inpefa treatment reduced risk by 22% in both the entire cohort and in the HF group. For patients with an ejection fraction of 40% to 50%, Inpefa reduced risk in the entire cohort by 39% and in the HF group by 43%. For patients with HFpEF, the medication reduced risk by 30% in the entire cohort and by 33% in the HF group. All results were statistically significant and were similar for men and women.