Long-Term Efficacy and Safety of Dapagliflozin in Patients with Inadequately Controlled Type 1 Diabetes—The DEPICT-1 Study
Authors: DANDONA PARESH , MATHIEU CHANTAL , PHILLIP MOSHE , HANSEN LARS , TSCHOEPE DIETHELM , THOREN FREDRIK A. , XU JOHN , LANGKILDE ANNA MARIA ,   DEPICT-1 INVESTIGATORS
Published: June 2018

In the short term (24-week) period of the Phase 3 study DEPICT-1, treatment with the SGLT2 inhibitor dapagliflozin (DAPA) as adjunct to adjustable insulin (INS) improved glycemic control and was well-tolerated in patients with inadequately controlled T1D (HbA1c 7.5-10.5%) (Lancet Diabetes Endocrinol. 2017;5:864-76). Here we describe the 28-week extension of DEPICT-1, assessing the 52-week efficacy and safety of DAPA in patients who completed the 24-week period. 747 patients in the DAPA 5 mg (n=250), 10 mg (n=270), or placebo (PBO; n=227) plus INS groups entered the long-term period (90% of the randomized patients); 85% completed the study. Reductions in HbA1c and body weight were maintained in the DAPA groups vs. PBO over 52 weeks (Table). The moderate decrease in HbA1c with DAPA was accompanied by a more substantial dose-dependent reduction in body weight. Total events of adjudicated definite DKA increased in the long-term period, with more in the DAPA groups vs. PBO at Week 52. Most were mild or moderate, with the primary cause related to missed insulin doses or pump failure. Adverse events (AEs), serious AEs, and hypoglycemic events were balanced between groups (Table).
In conclusion, DAPA plus INS provided a sustained reduction in HbA1c and body weight, and was well-tolerated, but increased events of DKA over 52 weeks in patients with inadequately controlled T1D.Efficacy outcomes at Week 52DAPA 5 mg + INS n=259*DAPA 10 mg + INS n=259*Placebo + INS n=260*A1c, % Week 52 adjusted mean change from baseline (SE) Difference vs PBO (95% CI). -0.27 (0.06) -0.33 (-0.49, -0.17). -0.31 (0.06) -0.36 (-0.53, -0.20). 0.06 (0.06) -Total body weight Week 52 adjusted mean percent change from baseline (SE) Difference vs PBO (95% CI). -2.80 (0.32) -2.95 (-3.83, -2.06). -4.39 (0.31) -4.54 (-5.40, -3.66). 0.15 (0.33) -Safety outcomes at Week 52, n (%)n=277†n=296†n=260†≥1 AE ≥1 SAE ≥1 related SAE ≥1 event of any hypoglycaemia ≥1 event of severe hypoglycaemia Events adjudicated as definite DKA ...Mild ...Moderate ...Severe215 (77.6) 37 (13.4) 8 (2.9) 227 (81.9) 29 (10.5) 12 (4.3) ...5 (1.8) ...3 (1.1) ...4 (1.4)236 (79.7) 40 (13.5) 13 (4.4) 241 (81.4) 25 (8.4) 10 (3.4) ...2 (0.7) ...6 (2.0) ...2 (0.7)189 (72.7) 30 (11.5) 2 (0.8) 212 (81.5) 30 (11.5) 5 (1.9) ...3 (1.2) ...1 (0.4) ...1 (0.4)AE, adverse event; CI, confidence interval; DAPA, dapagliflozin; PBO, placebo; INS, insulin; SAE, serious adverse event; SE, standard error. *n is the number of patients who received 52 weeks of treatment in the full analysis set (excludes the first 55 patients allocated to only DAPA groups due to an interactive voice response system randomization system error). †n is the number of patients who initiated the 24-week period in the safety analysis set (includes the first 55 patients incorrectly randomized to only DAPA groups). ‡Includes events monitored in both 24-week short-term period and 28-week extension.

Disclosure
P. Dandona: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca. Research Support; Self; AstraZeneca. C. Mathieu: Research Support; Self; Novo Nordisk A/S. Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Novo Nordisk A/S. Research Support; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Advisory Panel; Self; Sanofi. Research Support; Self; Merck Sharp & Dohme Corp.. Speaker's Bureau; Self; Merck Sharp & Dohme Corp.. Advisory Panel; Self; Merck Sharp & Dohme Corp.. Research Support; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Advisory Panel; Self; Eli Lilly and Company. Research Support; Self; Novartis AG. Speaker's Bureau; Self; Novartis AG. Advisory Panel; Self; Novartis AG, Bristol-Myers Squibb Company. Speaker's Bureau; Self; AstraZeneca. Advisory Panel; Self; AstraZeneca, Pfizer Inc., Janssen Pharmaceuticals, Inc., Boehringer Ingelheim GmbH. Speaker's Bureau; Self; Boehringer Ingelheim GmbH. Advisory Panel; Self; Hanmi Pharmaceutical. Research Support; Self; Roche Diagnostics Corporation. Advisory Panel; Self; Roche Diagnostics Corporation. Research Support; Self; Medtronic. Advisory Panel; Self; Medtronic, MannKind Corporation. Research Support; Self; Intrexon. Advisory Panel; Self; Intrexon, Dianax, UCB, Inc.. Research Support; Self; Abbott. M. Phillip: Other Relationship; Self; Sanofi, Medtronic MiniMed, Inc., Novo Nordisk A/S. Speaker's Bureau; Self; Eli Lilly and Company. Research Support; Self; Merck & Co., Inc., Bristol-Myers Squibb Company, Kamada, Lexicon Pharmaceuticals, Inc.. Other Relationship; Self; DreaMed Diabetes, Ltd.. Speaker's Bureau; Self; Abbott. L. Hansen: Employee; Self; MedImmune. D. Tschoepe: Advisory Panel; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca. Advisory Panel; Self; Amgen Inc.. Speaker's Bureau; Self; Amgen Inc.. Advisory Panel; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Novo Nordisk A/S. Advisory Panel; Self; Servier. Speaker's Bureau; Self; Servier, Sanofi, Novartis Pharmaceuticals Corporation. Research Support; Self; AstraZeneca, Bayer AG, Eli Lilly and Company, Novo Nordisk A/S, Novartis Pharmaceuticals Corporation, Sanofi. F.A. Thoren: Employee; Self; AstraZeneca. J. Xu: Employee; Self; AstraZeneca. A. Langkilde: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca.