Dandona P, et al. - The efficacy and safety of dapagliflozin as an add-on to adjustable insulin in patients with inadequately controlled type 1 diabetes were evaluated in this study. Among patients with inadequately controlled type 1 diabetes, dapagliflozin was found to be a promising adjunct treatment to insulin to improve glycaemic control.

• DEPICT-1 involved a double-blind, randomised, parallel-controlled, three-arm, phase 3, multicentre study performed at 143 sites in 17 countries.
• Patients aged 18-75 years, who had inadequately controlled type 1 diabetes (HbA_1c between ≥7·7% and ≤11·0% [≥61·0 mmol/mol and ≤97·0 mmol/mol]) and had been prescribed insulin for at least 12 months before enrolment were eligible for this study.
• Patients were randomly assigned (1:1:1) using an interactive voice response system to dapagliflozin 5 mg or 10 mg once daily, given orally, or matched placebo, after an 8 week lead-in period to optimise diabetes management.
• The researchers stratified randomisation by current use of continuous glucose monitoring, a method of insulin administration, and baseline HbA_1c.
• The change from baseline in HbA_1c after 24 weeks of treatment in the full analysis set, which consisted of all randomly assigned patients who received at least one dose of study drug was the primary efficacy outcome.
• The safety analysis set included an additional 55 patients, who were incorrectly and non-randomly allocated to only dapagliflozin treatment groups.

• The researchers assigned 833 patients to treatment groups and included in safety analyses (dapagliflozin 5 mg [n=277] vs dapagliflozin 10 mg [n=296] vs placebo [n=260] between Nov 11, 2014, and April 16, 2016.
• Out of them, 778 patients were randomly assigned and included in the full analysis set for efficacy analyses (259 vs 259 vs 260; difference due to randomisation error affecting 55 patients).
• Mean baseline HbA_1c was 8·53% (70 mmol/mol; SD 0·67% [7·3 mmol/mol]).
• Both doses of dapagliflozin significantly reduced HbA_1c compared with placebo (mean difference from baseline to week 24 for dapagliflozin 5 mg vs placebo was -0·42% [95% CI -0·56 to -0·28; p < 0·0001] and for dapagliflozin 10 mg vs placebo was -0·45% [-0·58 to -0·31; p < 0·0001]) at week 24.
• The most common adverse events were nasopharyngitis (38 [14%] vs 36 [12%] vs 39 [15%]), urinary tract infection (19 [7%] vs 11 [4%] vs 13 [5%]), upper respiratory tract infection (15 [5%] vs 15 [5%] vs 11 [4%]), and headache (12 [4%] vs 17 [6%] vs 11 [4%]) among patients in the dapagliflozin 5 mg (n=277), dapagliflozin 10 mg (n=296), and placebo (n=260) groups.
• In the dapagliflozin 5 mg, dapagliflozin 10 mg, and placebo groups, hypoglycaemia occurred in 220 (79%), 235 (79%), and 207 (80%) patients, respectively and severe hypoglycaemia occurred in 21 (8%), 19 (6%), and 19 (7%) patients, respectively.
• Adjudicated definite diabetic ketoacidosis occurred in 4 (1%) patients in the dapagliflozin 5 mg group, 5 (2%) in the dapagliflozin 10 mg group, and 3 (1%) in the placebo group.