SOTA inhibits sodium-glucose cotransporter (SGLT) 1 in the GI tract and SGLT2 in the kidney. Compared to selective SGLT2 inhibitors, SOTA potentially retains glycemic lowering despite renal insufficiency. This is the first study of an SGLT-inhibitor to examine glycemic control in patients with T2D and Stage 4 CKD.
In a 52-week, Phase 3 study, SOTA 200 and 400 mg QD were evaluated for superiority vs. placebo (PBO) in reducing HbA1C levels after 26 weeks. Adults had T2D, inadequate glycemic control (mean HbA1C, 8.0%), and severe CKD (mean eGFR, 23.6 mL/min/1.73 m2).
Pre-specified efficacy endpoint data analyzed by an ANCOVA model combining retrieved dropout and washout imputation methods for missing data showed clinically meaningful HbA1C reduction with SOTA 400 mg vs. PBO of -0.30% (95% CI: −0.61, 0.02; p=0.062). In an analysis consistent with FDA recommendations applying an ANCOVA model using just the retrieved dropout imputation method, SOTA 400 mg (n=92) reduced HbA1C vs. PBO (n=92) by −0.33% (95% CI: 0.66, −0.001; p=0.049) at Week 26. SOTA 200 mg did not significantly reduce HbA1C vs. PBO.
In key secondary endpoint analyses at Week 26, SOTA 400 mg reduced mean body weight vs. PBO by −1.53 kg (95% CI: −2.96, −0.09). In patients with baseline urinary albumin-to-creatinine-ratio (UACR) >30 mg/g, SOTA 400 mg reduced UACR vs. PBO by −27.04% (95% CI: −46.36, −0.75). At Week 12, SOTA 400 mg reduced SBP vs. PBO by −5.22 mm Hg (95% CI: −9.31, −1.13).
The incidence of adverse events was 77.8% with SOTA vs. 74.2% with PBO. There were no treatment-group differences in mycotic infection (0% vs. 0%) or volume depletion (0% vs. 4.3%). Rates of level 1 and 2 hypoglycemia were lower with both doses of SOTA vs. PBO.
At 26 weeks, SOTA 400 mg treatment resulted in meaningful reductions in HbA1C without unexpected safety concerns in adults with T2D and stage 4 CKD. The impact on renal and cardiovascular outcomes is being evaluated in a dedicated CVOT in patients with CKD.
D. Cherney: Research Support; Self; Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca and Novo-Nordisk. Other Relationship; Self; from Boehringer Ingelheim-Lilly, Merck, AstraZeneca, Sanofi, Mitsubishi-Tanabe, Abbvie, Janssen, Bayer, Prometic, BMS and Novo-Nordisk. E. Ferrannini: Consultant; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Oramed Pharmaceuticals. Research Support; Self; AstraZeneca, Janssen Pharmaceuticals, Inc. G.E. Umpierrez: None. A.L. Peters: Advisory Panel; Self; Abbott, Bigfoot Biomedical, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, MannKind Corporation, Medscape, Novo Nordisk Inc., Sanofi US. Consultant; Self; Livongo Health. Research Support; Self; Dexcom, Inc., vTv Therapeutics. Other Relationship; Self; Livongo Health, Mellitus Health, Omada Health, Stability Healthcare, Whole Biome Inc. J. Rosenstock: Research Support; Self; AstraZeneca, Bristol-Myers Squibb, Genentech, Inc., GlaxoSmithKline plc., Lexicon Pharmaceuticals, Inc., Oramed Pharmaceuticals, PegBio Co., Ltd., Pfizer Inc., REMD Biotherapeutics. Other Relationship; Self; Applied Therapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. A.K. Carroll: Employee; Self; Lexicon Pharmaceuticals, Inc. Stock/Shareholder; Self; Lexicon Pharmaceuticals, Inc. P. Lapuerta: Employee; Self; Lexicon Pharmaceuticals, Inc. Stock/Shareholder; Self; Lexicon Pharmaceuticals, Inc. P.L. Banks: Employee; Self; Lexicon Pharmaceuticals, Inc. W. Jiang: Employee; Self; Lexicon Pharmaceuticals, Inc. Stock/Shareholder; Self; Lexicon Pharmaceuticals, Inc. S. Sawhney: None.