Efficacy and safety of adding sotagliflozin, a dual sodium‐glucose co‐transporter (SGLT)1 and SGLT2 inhibitor, to optimized insulin therapy in adults with type 1 diabetes and baseline body mass index ≥ 27 kg/m²

Abstract

Sotagliflozin, a dual sodium‐glucose co‐transporter (SGLT)1/SGLT2 inhibitor, is currently approved in Europe as an adjunct to optimal insulin therapy in adults with type 1 diabetes (T1D) and a body mass index (BMI) ≥ 27 kg/m2. In this post hoc analysis, efficacy at 24 weeks and safety at 52 weeks from pooled phase 3 clinical trials were evaluated in patients with baseline BMI ≥ 27 kg/m2. Sotagliflozin 200 mg and 400 mg added to insulin reduced glycated haemoglobin level and increased time in range assessed by continuous glucose monitoring versus placebo and also reduced body weight and systolic blood pressure. Differences in efficacy endpoints between sotagliflozin and placebo tended to be greater among patients with BMI ≥ 27 kg/m2 compared to those with baseline BMI < 27 kg/m2. Consistent with published results for the entire population, fewer severe hypoglycaemia and documented hypoglycaemia ≤3.1 mmol/L events and a higher incidence of diabetic ketoacidosis occurred with sotagliflozin versus placebo in patients with BMI ≥ 27 kg/m2. Sotagliflozin as an adjunct to optimized insulin therapy in overweight/obese patients with T1D addressed some unmet needs and may help achieve optimal glycaemic control, mitigating weight gain without increasing hypoglycaemia risk in this high‐risk population.

C‐peptide determination in the diagnosis of type of diabetes and its management: A clinical perspective

“…A better risk-benefit ratio associated with the use of sodiumglucose co-transporter-2 (SGLT2) inhibitors among people with type 1 diabetes has been suggested among people with a body mass index (BMI) of 27 kg/m 2 or higher, 58,59 although a recent meta-analysis has also suggested that the risk of DKA increases with excessive insulin dose reduction, higher BMI and higher insulin resistance. 60 DKA might occur among users of SGLT2 inhibitors when there is an imbalance between the amount of insulin required to halt lipolysis and the amount of available (endogenous or exogenous) insulin.…”

Glucose-Lowering Therapy beyond Insulin in Type 1 Diabetes: A Narrative Review on Existing Evidence from Randomized Controlled Trials and Clinical Perspective

“…The risk of DKA was higher in persons randomized to sotagliflozin, and the risk of severe hypoglycemia was reduced in the sotagliflozin groups [82,83]. A post hoc analysis of the inTandem program revealed a more favorable efficacy and safety profile when sotagliflozin was used in persons with a BMI > 27 kg/m 2 compared to those with a BMI < 27 kg/m 2 [128]. Interestingly, in a recently published small study including 85 participants with not-well-controlled T1D and a younger age (18-30 years) receiving sotagliflozin 400 mg or placebo, the risk of DKA was not increased in the sotagliflozin group.…”

The safety of sotagliflozin in the therapy of diabetes mellitus type 1 and type 2: A meta-analysis of randomized trials

“…Exclusion criteria: (1) Study contained inappropriate subgroup analysis or single-arm treatment; (2) the research was not a phase II or phase III clinical trial; (3) the adverse events were absent in the article; (4) the research data was not able to be extracted; (5) The latest article will be selected and reviewed when it comes to duplicates.…”

“…SGLT2 is expressed in the kidney and could reabsorb 90% of the filtered glucose ( 2 ). Since insulin therapy alone cannot achieve adequate control of blood sugar in most DM patients ( 3 ), sotagliflozin, a dual inhibitor that targets SGLT1 and SGLT2 ( 4 ), was currently approved in Europe as the best auxiliary drug with insulin for the treatment of adults with DM and a body mass index (BMI) of ≥ 27 kg/m 2 ( 5 ). The primary metabolic effect of sotagliflozin is mediated by SGLT2-inhibition in the kidney, while some additional postprandial glucose control may be mediated by inhibition of SGLT1 in the intestine ( 3 , 4 , 6 – 9 ).…”

“…Sotagliflozin can prolong the local inhibitory effect of SGLT1 in the intestine in the aspect of absorption to ≥ 5 hours, resulting in an additional reduction in intestinal glucose absorption. The extended absorption can further/subsequently enhance the efficacy of SGLT2 inhibitors and ultimately reduce PPG and insulin levels ( 5 , 10 ); sotagliflozin can also lead to an increase in renal glucose excretion and a decrease in the early-stage glucose absorption, as well as an increase in GLP-1 and PYY ( 11 ). This is different from the SGLT2-selective inhibitors, such as dapagliflozin, empagliflozin, and ertugliflozin, which have a prominent role nowadays in the treatment of type 2 diabetes (T2D), cardiovascular and renal disease (especially dapagliflozin and empagliflozin).…”