Data Published on Sotagliflozin Used to Reduce HbA1c in Adults with Type 1 Diabetes and Kidney Disease
The data, published in JASN, were presented last week to an FDA advisory committee considering recommending sotagliflozin as an adjunct to insulin in adults with T1D and CKD.
In a population of adults with type 1 diabetes (T1D) and chronic kidney disease (CKD), treatment with sotagliflozin (Zynquista; Lexicon Pharmaceuticals) as an adjunct to insulin therapy had similar HbA1c-lowering effects as it did in individuals who did not have CKD. In addition, sotagliflozin was associated with a lower to neutral risk of severe hypoglycemia and the dual SGLT1/2 inhibitor did not increase the risk of diabetic ketoacidosis (DKA) among a small number of DKA events.1
The findings from the study, “Efficacy and Safety of Sotagliflozin in Patients with Type 1 Diabetes and CKD,” were published recently in the Journal of American Society of Nephrology (JASN), according to a news release from Lexicon.2
For the study, David Cherney, MD, PhD, University Health Network, University of Toronto, in Ontario, and colleagues used data from the 52-week pooled inTandem1 and 2 trials and the 24-week inTandem3 trial to assess the effects of sotagliflozin 200 mg (inTandem 1&2 only) ] or 400mg daily vs placebo on HbA1c, the study’s primary endpoint, and on body weight, systolic blood pressure (SBP), insulin dose, and safety endpoints. Specific safety outcomes included adjudicated severe hypoglycemia and DKA, in each case stratified by CKD.1
Of the 1575 participants in the inTandem1 and 2 trials, 237 were identified who had CKD. Of the 1402 individuals enrolled in the inTandem3 trial, 228 were identified who had CKD.
After 24 weeks of treatment, Cherney and colleagues observed significant, placebo-adjusted reductions in HbA1c in inTandem1 and 2:
- Non-CKD subgroup (sotagliflozin 200mg: -0.4%, 95% CI -0.4 to -0.3; 400mg: -0.4%, 95% CI -0.5 to -0.3)
- CKD subgroup (sotagliflozin 200mg: -0.4%, 95% CI -0.6 to -0.1; 400mg: -0.3%, 95% CI -0.5 to -0.1)
SBP. In the non-CKD group, investigators reported a significant placebo-adjusted reduction in systolic BP at week 24 with sotagliflozin. However, no effect on SBP was seen in the subgroup with CKD in the inTandem1 and 2 studies.1
Hypoglycemia. At week 52, there was a lower incidence of severe hypoglycemia observed with sotagliflozin (7% on 200 mg and 4% on 400 mg) vs placebo (17%) in the CKD subgroup of inTandem1 and 2, whereas the incidence was 5-6% across both sotagliflozin and placebo non-CKD subgroups.
DKA. The incidence of adjudicated DKA at week 52 in inTandem 1 and 2 was 1%, 5%, and 3%, respectively, for the placebo, 200 mg, and 400 mg doses in the CKD subgroup, compared to 0%, 3%, and 4% in the non-CKD subgroup.1
The researchers found generally similar results in the inTandem3 study however SBP was significantly reduced with sotagliflozin vs placebo in CKD and non-CKD subgroups.
“There hasn’t been a new drug approved for patients living with type 1 diabetes and chronic kidney disease in decades," co-author Cherney said in the Lexicon announcement.2 “Previous studies have shown the SGLT inhibitors - including sotagliflozin - lower blood pressure and harmful urinary protein levels to a similar degree in people with type 1 diabetes compared to people with type 2 diabetes. Our current analysis adds important evidence showing that sotagliflozin has the potential to provide benefits for patients with type 1 diabetes and chronic kidney disease, particularly when appropriate steps are taken to reduce the risk of diabetic ketoacidosis.”2
“People with T1D and CKD urgently need new treatment options,” added Craig Granowitz, MD, PhD, Lexicon senior vice president and chief medical officer. “We believe the findings of this analysis support our position that, if approved by the FDA, sotagliflozin should be included in discussions between clinicians and their patients with T1D and CKD about how to best achieve glycemic control.”2
As Patient Care has previously reported, the FDA assigned a Prescription Drug User Fee Act (PDUFA) target action date for sotagliflozin of December 20, 2024. In an update published November 1, we reported on the FDA Endocrinologic and Metabolic Drugs Advisory Committee’s 11 to 3 vote against recommending the SGLT1/SLGT2 inhibitor to treat adults with T1D and CKD. The PDUFA has not been changed.
References
References
1. Sridhar VS, Odutayo A, Garg S, et al. Efficacy and safety of Sotagliflozin in patients with type 1 diabetes and CKD. JASN. Published online November 1, 2024. doi:10.1681/ASN.0000000540
2. Published data in Journal of American Society of Nephrology highlights findings of efficacy and safety of sotagliflozin for people with type 1 diabetes and chronic kidney disease. News release. Lexicon Pharmaceuticals. November 5, 2024. Accessed November 7, 2024. https://www.lexpharma.com/media-center/news/2024-11-05-published-data-in-journal-of-american-society-of-nephrology-highlights-findings-on-efficacy-and-safety-of-sotagliflozin-for-people-with-type-1-diabetes-and-chronic-kidney-disease
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