Long‐term efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes: pooled 52‐week outcomes from the DEPICT‐1 and ‐2 studies

• Published in: Diabetes, obesity & metabolism obesity & metabolism, 2021-02, Vol.23 (2), p.549-560
• Main Authors: Phillip, Moshe, Mathieu, Chantal, Lind, Marcus, Araki, Eiichi, Bartolo, Paolo, Bergenstal, Richard, Heller, Simon, Hansen, Lars, Scheerer, Markus Florian, Thoren, Fredrik, Arya, Niki, Xu, John, Iqbal, Nayyar, Dandona, Paresh
• Format: Article
• Language: English
• Subjects: Adult; Antidiabetics; association; Benzhydryl Compounds - adverse effects; Body weight; dapagliflozin; dapagliflozin, DEPICT, DKA, insulin adjunct, long‐term data, severe hypoglycaemia, SGLT‐2 inhibitor, T1D; DEPICT; Diabetes; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1 - drug therapy; Diabetic ketoacidosis; DKA; Double-Blind Method; Drug Therapy, Combination; Endocrinology & Metabolism; Endocrinology and Diabetes; Endokrinologi och diabetes; glucose cotransporter inhibitors; Glucosides - adverse effects; Glycated Hemoglobin A - analysis; glycemic control; Humans; hyperglycemia; hypoglycaemia; Hypoglycemia; Hypoglycemic Agents - adverse effects; Insulin; insulin adjunct; Ketoacidosis; long-term data; mellitus; Original; Placebos; Safety; severe; SGLT-2 inhibitor; sglt2 inhibitor; T1D; Treatment Outcome
• ISSN: 1462-8902; 1463-1326
• DOI: 10.1111/dom.14248

Aim To evaluate the efficacy and safety of adjunct dapagliflozin therapy in patients with type 1 diabetes (T1D). Materials and Methods DEPICT‐1 and ‐2 were randomized, double‐blind, parallel‐group, 24‐week studies, with 28‐week extension periods. Adults with T1D and HbA1c 7.5%‐10.5% were randomized (1:1:1) to receive dapagliflozin 5 mg, 10 mg or placebo. The short‐ and long‐term efficacy and safety of dapagliflozin were examined in an exploratory pooled analysis of both studies. Results Efficacy analyses included 530, 529 and 532 and safety analysis included 548, 566 and 532 patients in the dapagliflozin 5 mg, 10 mg and placebo groups, respectively. Baseline characteristics were similar between treatment groups. At week 24, reductions were seen with dapagliflozin 5 and 10 mg compared with placebo in HbA1c (−0.40%, −0.43% vs. 0.00%) and body weight (−2.45, −2.91 vs. 0.11 kg). HbA1c and body weight reductions versus placebo were also seen after 52 weeks of treatment. There was no imbalance in occurrence of severe hypoglycaemic events between groups. The proportion of patients experiencing definite diabetic ketoacidosis (DKA) was higher with dapagliflozin 5 mg (4.0%) and 10 mg (3.5%) compared with placebo (1.1%) over 52 weeks; most events were of mild or moderate severity, and all resolved with treatment. Conclusions Over 52 weeks, dapagliflozin provided glycaemic and weight benefits, with no increased frequency of severe hypoglycaemia compared with placebo. More DKA events were reported with dapagliflozin than placebo, highlighting the importance of appropriate patient selection, education and risk‐mitigation strategies.