Efficacy and Safety of Sotagliflozin in Patients with Type 1 Diabetes and CKD
Bibliographic record
Abstract
Background: People with T1D, chronic kidney disease (CKD) and poor glycemic control are at high risk of kidney failure and cardiovascular events. Sodium-glucose cotransporter (SGLT) inhibitors improve glycemic control in adults with T1D but with an increased risk of diabetic ketoacidosis (DKA). This post hoc analysis evaluated the efficacy and safety of sotagliflozin (SOTA), a dual SGLT1 & 2 inhibitor, in patients with T1D and CKD. Methods: Using patient-level data from in Tandem 1 & 2, the effects of SOTA (200 or 400 mg daily) added to optimized insulin therapy on A1C, body weight (BW), systolic blood pressure (SBP), eGFR, total insulin dose, adjudicated severe hypoglycemia (SH) and DKA were compared to placebo in a patient subgroup with T1D and CKD (eGFR <60 mL/min/1.73 m2 and/or UACR ≥30 mg/g). Results: In the 1575 patients, 237 (15%) had CKD. At baseline, patients with CKD were older, had longer T1D duration, lower eGFR, lower insulin pump use, higher total daily insulin dose, SBP, and UACR compared to the overall cohort. Relative to placebo, treatment with SOTA provided similar significant reductions in A1C, SBP and BW in the CKD and overall cohorts, but numerically smaller % reduction in total insulin dose at week 24 in the CKD cohort (Table 1). SOTA vs.placebo was associated with lower SH and higher DKA risk. However, the relative risk of SH and DKA appeared to be lower in the CKD vs. overall cohort over 52 weeks (Table 1). The expected acute eGFR decline followed by stabilization with SOTA was preserved in the CKD cohort. Table 1. - Selected key efficacy and safety endpoints by study treatment and cohort. CKD Cohort Overall Cohort Placebo N = 76 Sotagliflozin 200 mg N = 85 Sotagliflozin 400 mg N = 76 Placebo N = 526 Sotagliflozin 200 mg N = 524 Sotagliflozin 400 mg N = 525 AIC, % -0.13 (-0.29, 0.03) -0.48 (-0.63, -0.33)* -0.45 (-0.61, -0.29)* -0.13 (-0.29, 0.03) -0.48 (-0.63, -0.33)* -0.45 (-0.61, -0.29)* Body weight, kg -0.15 (-0.83, 0.53) -1.55 (-2.20, -0.91)* -2.58 (-3.25, -1.91)* 0.47 (0.20, 0.74) -1.70 (-1.97, -1.44)* -2.55 (-2.82, -2.28)* SBP, mmHg -2.1 (-5.0, 0.7) -4.8 (-7.5, -2.0) -6.9 (-9.7, -4.1)* -0.6 (-1.5, 0.3) -2.6 (-3.5, -1.7)* -4.1 (-5.0, -3.2)* Total insulin dose, % 0.4 (-3.5, 4.2) -4.2 (-8.0, -0.5) -5.2 (-9.0, -1.4)** 1.1 (-0.5, 2.8) -6.1 (-7.7, -4.4)* -8.4 (-10.1, -6.8)* Severe hypoglycemia, n (%) 13 (17.1) 6 (7.1) 3 (3.9) 39 (7.4) 30 (5.7) 23 (4.4) HR (95% CI) - 0.34 (0.13, 0.91) 0.20 (0.06, 0.70) - 0.76 (0.47, 1.22) 0.58 (0.35, 0.97) DKA, n (%) 1 (1.3) 4 (4.7) 2 (2.6) 1 (0.2) 15 (2.9) 20 (3.8) HR (95% CI) - 3.2 (0.4, 29.0) 1.9 (0.2, 20.8) - 15.0 (2.0, 113.3) 20.3 (2.7, 151.2) HR = Hazard Ratio, CI = confidence interval.*p<0.01,**p<0.05 for the difference in LS mean change between sotagliflozin and placebo.Efficacy endpoints were presented as LS mean change from baseline at Week 24 (95% CI) to be consistent with the primary endpoint time point in the individual trials.Safety endpoints were presented from the entire 52 week follow up plus 30 days after last study dose. Conclusions: In patients with T1D and CKD, treatment with SOTA had similar A1C and SBP lowering effects, and a lower relative risk of SH and DKA vs. the overall cohort. Funding: Commercial Support - Lexicon Pharmaceuticals
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".