Sotagliflozin is a new dual target medication for sodium-glucose cotransporter 1 (SGLT1) and SGLT2. It has shown strong effects on lowering A1c and body weight, helping patients regardless of their level of kidney function. In March 2023, the US Food and Drug Administration (FDA) approved sotagliflozin. This drug addresses the dangers of cardiovascular mortality, hospitalization for heart failure and visit to emergency department for heart failure. This approval is particularly relevant for patients with heart failure, type 2 diabetes, chronic kidney disease (CKD), and other cardiovascular disease risk factors.
The FDA’s approval came on the heels of an extensive meta-analysis of those eight double-blind, randomized, placebo-controlled trials. Both trials were 26 weeks or longer in duration and set a strong stage for evaluating the efficacy of sotagliflozin. Participants were categorized into three distinct subgroups based on their estimated glomerular filtration rate (eGFR): those with normal kidney function (eGFR ≥ 60 mL/min/1.73m²), moderate impairment (eGFR ≥ 30 to < 60 mL/min/1.73m²), and severe impairment (eGFR < 30 mL/min/1.73m²).
In the end, 4,688 patients enrolled in the study. They were randomized to receive 400 mg or 200 mg sotagliflozin or placebo. The mean ages of the patients varied by subgroup: 60.2 years in subgroup 1, and 69.3 years and 67.1 years in subgroups 2 and 3, respectively.
Sotagliflozin produced significantly greater reductions in A1c levels than placebo. The 200-mg dose was able to reach a reduction of –0.33, but the 400-mg dose doubled down with a larger reduction of –0.48. Body weight decreased considerably within each dosing group. Participants on the 200-mg dose gained an average of 1.48 kg, and participants on the 400-mg dose lost an average of 1.66 kg.
In subgroup 1, the improvements in A1c and body weight were statistically significant in all cases. Subgroup 2 had the greatest weight loss effects with both doses. Only the higher dose resulted in a clinically significant decrease in A1c levels. The 400-mg dosage provided significant improvements among all eGFR subgroup analyses with the exception of A1c reduction in subgroup 3.
“This opens my mind more that if there is a heart failure patient with diabetes and we’re looking for sugar reduction as well as heart failure protection, sotagliflozin is probably just as efficacious as the SGLT2 inhibitors that have the indication for glucose-lowering, but we’re not pulling it out as a first-line treatment.” – Sara E. Lubitz, MD
While sotagliflozin appeared to hold great potential, it faced an uphill battle in the approval process. The FDA turned down its use for treating type 1 diabetes in 2019, citing risk of higher diabetic ketoacidosis. In what would prove to be a big misstep, the FDA rejected Lexicon Pharmaceuticals’ application yet again. This time, it was for their application to treat people living with type 1 diabetes and chronic kidney disease (CKD).
Belinda Hardin, PharmD, underscored the importance of considering kidney function. This consideration is important to take into account when treating patients with diabetes and CKD. She stated:
“These findings highlight the importance of considering the effect of kidney function to help inform and tailor treatment decision-making for patients with diabetes and CKD.”
Hardin emphasized that the data provides unprecedented detail into a four-year time horizon for heart failure outcomes. It fails to highlight the extra benefits of A1c levels or their lowering in this patient demographic.
“This provides us supplemental information with regard to heart failure outcomes, and not directly focusing on whether there’s an additive benefit in terms of A1c or an additive lowering of A1c in patients with chronic kidney disease.” – Belinda Hardin, PharmD
As of this writing, what future FDA filings for sotagliflozin might entail remains unclear. This drug is primarily to be used as glucose-lowering agent in patients with type 2 diabetes mellitus. According to Hardin:
“I don’t think at this point you’ll likely see sotagliflozin before the FDA for a glucose-lowering indication in type 2 patients. The file remains open for type 1 at the FDA, so that work continues.” – Belinda Hardin, PharmD
Leave a Reply