Sotagliflozin as adjunct to insulin: New SGLT1/SGLT2 inhibitor lowers HbA1c and has less hypoglycemia episodes among people who have type 1 diabetes.
Sodium-glucose cotransporter 2 inhibitors (SGLT-2) lower blood sugar by causing the kidneys to remove sugar from the body through the urine. SGLT-1 inhibitors are a novel development that blocks a transporter responsible for glucose and galactose absorption in the gastrointestinal tract. Combining SGLT-1 and -2 inhibitors may have a better effect on lowering blood glucose, thereby reducing A1c. The safety and efficacy of SGLT-2 inhibitors have not been demonstrated in patients with type 1 diabetes, and FDA has not approved them for use in these patients.
A new drug called sotagliflozin is a dual inhibitor of SGLT-1 and SGLT-2. This decreases renal glucose reabsorption and reduces glucose absorption in the proximal intestine. Its safety and efficacy are the main topics in a recently published article on sotagliflozin use in people with type 1 diabetes. The study focuses on reduction in HbA1c as its primary endpoint, and hypoglycemia and diabetic ketoacidosis (DKA), which are major safety issues for SGLT-2 inhibitors. The study lasted 24 weeks with an extension to 52 weeks.
In this phase 3, multicenter, double-blind, randomized study, oral sotagliflozin 200mg, 400mg, or placebo was given to people with type 1 who have consistently high blood glucose along with optimal insulin doses. Insulin dosing was optimized pre-trial for six weeks by diabetes specialists. After six weeks, HbA1c was taken and patients were randomized. For the following 24 weeks, participants and staff did not have access to doses or HbA1c levels; after 24 weeks the data was unmasked and other endpoints were evaluated, including body weight, bolus insulin dose, and fasting glucose changes until week 52. A total of 793 patients were involved in the study and efficacy analyses were based on the intent-to-treat population. Characteristics at baseline were similar between groups and about 60% of participants used an insulin pump while 40% used multiple daily injections for insulin administration.
Prior to the start of the trial, insulin optimization improved HbA1c by 0.65%. At week 24, the placebo-adjusted least square mean HbA1c was reduced by an additional 0.36% in the 200mg sotagliflozin group and 0.41% in the 400mg sotagliflozin group. At week 52, patients taking sotagliflozin had reduced HbA1c, weight, bolus insulin, and fasting glucose levels compared to placebo. The least square mean difference for weight loss compared with placebo was -3.14kg (P<0.001) for the 200mg dose and -4.32kg (P<0.001) for the 400mg dose. Those with a systolic blood pressure over 130 mmHg at baseline saw a significant reduction by week 52.
The use of sotagliflozin resulted in less hypoglycemia compared to those only taking insulin, but there was an increased risk of DKA. Of the patients on sotagloflozin, 3.4% and 4.2% in the 200mg and 400mg group experienced DKA, respectively. Only one patient (0.4%) had DKA in the placebo. Severe hypoglycemia occurred in the placebo group with 9.7% versus 6.5% in both sotagliflozin groups. Overall, patients taking sotagliflozin had a greater clinical net benefit of lower average blood glucose levels without severe hypoglycemia. There was a net benefit in 19% of patients in the placebo group versus 26.2% and 32.4% in the 200mg and 400mg groups, respectively.
The challenges in type 1 diabetes are unique. Insulin can have side effects like weight gain, and its management needs to be very tight to keep blood glucose at goal levels. The fear of hypoglycemia is a real issue also with insulin injections. Sotagliflozin as an adjunct to insulin therapy in type 1 diabetes seemed to address these challenges and would be beneficial to help manage blood glucose in people with type 1 diabetes.
- Sotagliflozin is a new SGLT-1/SGLT-2 inhibitor being studied for use in people with type 1 diabetes.
- Patients taking sotagliflozin had lower average blood glucose levels with less severe hypoglycemia episodes.
- There is an increased risk of DKA, so patient education and monitoring are key.
Sotagliflozin as adjunct to insulin – References:
John B. Buse, Satish K. Garg, Julio Rosenstock, Timothy S. Bailey, Phillip Banks, Bruce W. Bode, Thomas Danne, Jake A. Kushner, Wendy S. Lane, Pablo Lapuerta, Darren K. McGuire, Anne L. Peters, John Reed, Sangeeta Sawhney and Paul Strumph. Sotagliflozin in Combination With Optimized Insulin Therapy in Adults With Type 1 Diabetes: The North American in Tandem1 Study. Diabetes Care (2018) https://doi.org/10.2337/dc18-0343