The aim of this retrospective study conducted in two centres in Spain and Belgium was to evaluate the safety and efficacy of sodium–glucose cotransporter 2 (SGLT2) inhibitors, as an adjunct to insulin therapy, in a real-world cohort of people with type 1 diabetes. Data from 199 people were analysed, of whom 113 received empagliflozin, 66 dapagliflozin and 20 canagliflozin. The mean age was 48 years and the mean diabetes duration 26 years.
At 12 months after initiation, mean HbA1c reduced significantly by 5 mmol/mol (0.5%), with the greatest reductions seen in those with higher HbA1c and higher BMI at baseline. Mean body weight was reduced by 2.9 kg. Both benefits were achieved at 8 months and were sustained at 12 months. In addition, total daily insulin requirements reduced by a mean of 8.5%.
In the overall cohort, improvements in renal function at 12 months were not significant; however, most participants had normal renal function at baseline. In those with renal impairment at baseline, mean eGFR increased from 80.1 to 84.6 mL/min/1.73 m2, while a 52% reduction in urinary ACR was seen in those with ACR ≥15 mg/g at baseline.
Fifty-seven of 199 participants (28.6%) had one or more adverse event over the study period: 45 genital infections, five incidences of elevated ketones without acidosis, seven of diabetic ketoacidosis (DKA) and one of severe polyurea. No severe hypoglycaemia was recorded over the study period. Fifteen people discontinued due to adverse events and four stopped due to lack of effect.
DKA was more common in insulin pump than multiple daily injection users (6.2% vs 2.2%), in women than in men (5.3% vs 1.2%) and in individuals with a BMI of ≤27 kg/m2 compared with a higher BMI (4.8% vs 2.9%). Notably, no DKA was recorded where the EMA label of dapagliflozin was followed (dapagliflozin 5 mg once daily and BMI >27 kg/m2; n=20).
At initiation, all participants gave informed consent to use the agents on- or off-label, all were educated on prevention, recognition and treatment of DKA, and all were supported to monitor their ketone levels at home.
The authors conclude that SGLT2 inhibitors are effective combinations with insulin therapy in people with type 1 diabetes, although DKA remains a matter of concern, with careful case selection required for the best balance between risks and benefits. Since this study was conducted, the manufacturer has withdrawn the licence for dapagliflozin in type 1 diabetes.
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