Meta-analysis demonstrates benefits of add-on sotagliflozin in type 1 diabetes
medwireNews: Adding the sodium-glucose cotransporter (SGLT)1/2 inhibitor sotagliflozin to insulin treatment improves glycemic and non-glycemic outcomes among people with type 1 diabetes, but at the cost of an increased risk for diabetic ketoacidosis (DKA), researchers report in The BMJ.
The meta-analysis included six randomized controlled trials comparing sotagliflozin with placebo on a background of insulin, involving a total of 3238 participants who were followed up for between 4 and 52 weeks.
Giovanni Musso (Humanitas University Gradenigo Hospital, Turin, Italy) and study co-authors found that sotagliflozin was associated with a significant reduction in glycated hemoglobin (HbA1c) levels compared with placebo, with a weighted mean difference of 0.34%.
Moreover, participants given sotagliflozin had significantly lower fasting plasma glucose and daily total, basal, and bonus insulin dose than those in the placebo group (weighted mean difference=16.98 mg/dL, 8.99%, 8.03%, and 9.14%, respectively), as well as significantly greater time spent in the target range during continuous glucose monitoring (weighted mean difference=9.73%). Rates of hypoglycemia and severe hypoglycemia events were significantly lower in the sotagliflozin group.
Musso and team also demonstrated significant improvements in non-glycemic endpoints associated with sotagliflozin, with individuals treated with the SGLT1/2 inhibitor experiencing a significant reduction in bodyweight and systolic blood pressure compared with those in the placebo group.
“These effects make sotagliflozin an attractive adjunctive treatment to insulin in patients with type 1 diabetes, of whom 30% achieve target glycaemic goals, 40% are overweight, and up to 20% per year experience severe hypoglycaemia,” they write.
However, sotagliflozin was associated with an almost fourfold higher risk for diabetic ketoacidosis compared with placebo (relative risk [RR]=3.93), in addition to a significantly increased risk for mycotic genital tract infections (RR=3.12) and diarrhea (RR=1.50).
In subgroup analyses, sotagliflozin was associated with a significantly elevated risk for ketoacidosis in trials with an average HbA1c below 8% at baseline, but not in those with a higher baseline mean HbA1c. Using a meta-regression model, the researchers showed that both initial HbA1c levels and the magnitude of basal insulin dose reduction correlated inversely with ketoacidosis risk.
Therefore, “[t]he risk of diabetic ketoacidosis could be minimised by appropriate patient selection and down-titration of the basal insulin dose,” say Musso et al.
The study authors caution that their study was limited by “the relatively small number and short duration of included trials […] which prevented robust assessment of long term hard outcomes such as [major adverse cardiovascular events] and overall mortality.”
Nonetheless, they believe that their findings, based on trials with good methodological quality, will have a “direct impact” on decision making in the care of people with type 1 diabetes.
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BMJ 2019; 365: l1328