Sotagliflozin, a Dual SGLT1 and SGLT2 Inhibitor, as Adjunct Therapy to Insulin in Type 1 Diabetes

Abstract

OBJECTIVETo assess the safety and efficacy of dual sodium–glucose cotransporter (SGLT) 1 and SGLT2 inhibition with sotagliflozin as adjunct therapy to insulin in type 1 diabetes.RESEARCH DESIGN AND METHODSWe treated 33 patients with sotagliflozin, an oral dual SGLT1 and SGLT2 inhibitor, or placebo in a randomized, double-blind trial assessing safety, insulin dose, glycemic control, and other metabolic parameters over 29 days of treatment.RESULTSIn the sotagliflozin-treated group, the percent reduction from baseline in the primary end point of bolus insulin dose was 32.1% (P = 0.007), accompanied by lower mean daily glucose measured by continuous glucose monitoring (CGM) of 148.8 mg/dL (8.3 mmol/L) (P = 0.010) and a reduction of 0.55% (5.9 mmol/mol) (P = 0.002) in HbA1c compared with the placebo group that showed 6.4% reduction in bolus insulin dose, a mean daily glucose of 170.3 mg/dL (9.5 mmol/L), and a decrease of 0.06% (0.65 mmol/mol) in HbA1c. The percentage of time in target glucose range 70–180 mg/dL (3.9–10.0 mmol/L) increased from baseline with sotagliflozin compared with placebo, to 68.2% vs. 54.0% (P = 0.003), while the percentage of time in hyperglycemic range >180 mg/dL (10.0 mmol/L) decreased from baseline, to 25.0% vs. 40.2% (P = 0.002), for sotagliflozin and placebo, respectively. Body weight decreased (1.7 kg) with sotagliflozin compared with a 0.5 kg gain (P = 0.005) in the placebo group.CONCLUSIONSAs adjunct to insulin, dual SGLT1 and SGLT2 inhibition with sotagliflozin improved glycemic control and the CGM profile with bolus insulin dose reduction, weight loss, and no increased hypoglycemia in type 1 diabetes.

Efficacy and Safety of Canagliflozin, a Sodium–Glucose Cotransporter 2 Inhibitor, as Add-on to Insulin in Patients With Type 1 Diabetes

“…DKA events have also been reported in pilot studies with other SGLT2 inhibitors in patients with type 1 diabetes. In a 4-week study with sotagliflozin, 2 of 16 patients in the sotagliflozin arm had a serious AE of DKA compared with no patients in the placebo arm (19). In an 8-week openlabel study with empagliflozin, 2 of 40 patients experienced a DKA AE (18).…”

“…Several small pilot studies with SGLT2 inhibitors, ranging from 2 to 8 weeks, have been performed in patients with type 1 diabetes (17)(18)(19). These studies have generally shown that treatment with SGLT2 inhibitors provides improved glucose control and reductions in the insulin dose without increasing hypoglycemic events.…”

Sodium-glucose Co-transporter-2 Inhibitors in Type 1 Diabetes—a Dangerous Ally

“…The reduction in post-meal glucose was associated with reduction in bolus insulin doses, not seen earlier with empagliflozin or dapagliflozin. 39,41 DKA events were higher with sotagliflozin. In a recent international phase 3 double blind randomized trials in patients with T1D using multiple subcutaneous insulin or pump therapy, the in Tandem 2 study (782 participants), the efficacy and safety of sotagliflozin 400 mg, sotagliflozin 200 mg versus placebo was assessed over 52 weeks.…”

“…39 SGLT1 mediates the intestinal absorption of glucose and galactose and renal glucose reabsorption distal to SGLT2 effect.…”

Association of British Clinical Diabetologists (ABCD) position statement on the risk of diabetic ketoacidosis associated with the use of sodium-glucose cotransporter-2 inhibitors

“…2,7,8 A much higher incidence was reported in trials with type 1 diabetes. [9][10][11][12][13][14][15] There were 147 cases recorded in the EudraVigilance database in the post marketing phase of the SGLT-2 inhibitors. 16 A recent meta-analysis of 10 eligible RCTs involving 13,134 patients and 14 DKA events found an overall event rate of 0.1% in the SGLT-2 inhibitor group versus 0.06% in the control group (ns).…”