In people with type 2 diabetes, sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce cardiovascular risk and progression of diabetic kidney disease. Our aim was to determine whether sotagliflozin (SOTA), a dual SGLT1i and SGLT2i, had favorable effects on clinical biomarkers suggestive of kidney protection in adults with type 1 diabetes. RESEARCH DESIGN AND METHODS In this 52-week pooled analysis, 1,575 adults enrolled in the inTandem1 and inTandem2 trials were randomized to SOTA 200 mg, 400 mg, or placebo in addition to optimized insulin therapy. Changes in cardiorenal biomarkers were assessed. RESULTS At 52 weeks, in response to SOTA 200 and 400 mg, the placebo-corrected least squares mean change from baseline in estimated glomerular filtration rate was 22.0 mL/min/1.73 m 2 (P = 0.010) and 20.5 mL/min/1.73 m 2 (P = 0.52), respectively. Systolic blood pressure difference was 22.9 and 23.6 mmHg (P < 0.0001 for both); diastolic blood pressure changed by 21.4 (P = 0.0033) and 21.6 mmHg (P = 0.0008). In participants with baseline urinary albumin-to-creatinine ratio (UACR) ‡30 mg/g, UACR decreased by 23.7% (P = 0.054) and 18.3% (P = 0.18) for SOTA 200 and SOTA 400 mg, respectively, versus placebo. Increases in serum albumin and hematocrit and reductions in uric acid were observed throughout 52 weeks with both SOTA doses. CONCLUSIONS SOTA was associated with short-and long-term renal hemodynamic changes, which were similar to those seen with SGLT2i in type 2 diabetes. Further investigation around cardiorenal effects of SOTA in people with type 1 diabetes is justified. Diabetic kidney disease occurs in ;20-40% of people with type 1 diabetes despite management of traditional renal risk factors (1). Sodium-glucose cotransporter 2 inhibitors (SGLT2i) act by blocking tubular glucose reuptake, leading to glucosuria and thereby lowering HbA 1c and body weight. In addition to glucosuric effects, SGLT2i are natriuretic, leading to contraction of plasma volume, systolic blood pressure (SBP) lowering, and increases in hematocrit and serum albumin (2,3). Natriuresis also attenuates glomerular hyperfiltration by lowering intraglomerular pressure via activation of tubuloglomerular feedback, an effect that has been shown in mechanistic
Background: Hypoglycemia rates usually increase when insulin treatment is intensified to improve glycemic control. We evaluated (post hoc) hypoglycemic rates in adult patients with type 1 diabetes (T1D) on sotagliflozin (a dual sodium-glucose cotransporter [SGLT] 1 and 2 inhibitor) in two phase 3, 52-week clinical trials (inTandem 1 and 2; NCT02384941 and NCT02421510). Materials and Methods: We analyzed rates of documented hypoglycemia (level 1, blood glucose ‡54 to <70 mg/dL) and clinically important hypoglycemia (level 2, glucose <54 mg/dL) in a patient-level pooled analysis (n = 1362) using a negative binomial model adjusted for hemoglobin A1c (HbA1c) at 52 weeks in patients receiving placebo, sotagliflozin 200 mg, and sotagliflozin 400 mg.
Funding information Lexicon Pharmaceuticals, Inc. designed and funded the studies, including the operational execution and medical monitoring of the studies. Sanofi and Lexicon Pharmaceuticals, Inc. entered a licence agreement effective from
Purpose: The purpose of this study was to conduct qualitative participant interviews to provide context to the meaningfulness of improvements in end points seen in 2 large-scale Phase III sotagliflozin trials in participants with type 1 diabetes. Methods: Participants were eligible for an interview if they had exited one of the clinical trials within the previous 12 months. Participants were recruited by investigators at the clinical trial sites, and interviews were conducted by independent interviewers by telephone in accordance with a semistructured interview guide. Both interviewers and participants were blinded to treatment assignment. Qualitative analysis was conducted using ATLAS-ti version 7.5, and descriptive statistics were computed and summarized. Findings: Across 3 countries, 41 participants were interviewed. Difficulty maintaining blood glucose within a desired range, described by participants as lack of blood glucose "stability," was the most concerning symptom that they reported, wanting to see it improved during the clinical trial because it negatively impacted their physical, mental, and emotional lives. Participants who reported symptom improvement also reported a positive psychosocial impact while taking the clinical trial medication. All participants who monitored ketones described gov identifiers: NCT02384941; NCT02421510.
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