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This study evaluated the long-term safety and efficacy of dapagliflozin as an adjunct to adjustable insulin in patients with type 1 diabetes and inadequate glycemic control. RESEARCH DESIGN AND METHODS DEPICT-1 (Dapagliflozin Evaluation in Patients With Inadequately Controlled Type 1 Diabetes) was a randomized (1:1:1), double-blind, placebo-controlled phase 3 study of dapagliflozin 5 mg and 10 mg in patients with type 1 diabetes (HbA 1c 7.5-10.5% [58-91 mmol/mol]) (NCT02268214). The results of the 52-week study, consisting of the 24-week short-term and 28-week extension period, are reported here. RESULTS Of the 833 patients randomized into the study, 708 (85%) completed the 52-week study. Over 52 weeks, dapagliflozin 5 mg and 10 mg led to clinically significant reductions in HbA 1c (difference vs. placebo [95% CI] 20.

Choices for the treatment of type 2 diabetes mellitus (T2DM) have multiplied as our understanding of the underlying pathophysiologic defects has evolved. Treatment should target multiple defects in T2DM and follow a patient-centered approach that considers factors beyond glycemic control, including cardiovascular risk reduction. The American Association of Clinical Endocrinologists/American College of Endocrinology and the American Diabetes Association recommend an initial approach consisting of lifestyle changes and monotherapy, preferably with metformin. Therapy choices are guided by glycemic efficacy, safety profiles, particularly effects on weight and hypoglycemia risk, tolerability, patient comorbidities, route of administration, patient preference, and cost. Balancing management of hyperglycemia with the risk of hypoglycemia and consideration of the effects of pharmacotherapy on weight figure prominently in US-based T2DM recommendations, whereas less emphasis has been placed on the ability of specific medications to affect cardiovascular outcomes. This is likely because, until recently, specific glucose-lowering agents have not been shown to affect cardiorenal outcomes. The Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUTCOME), the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial, and the Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes 6 (SUSTAIN-6) recently showed a reduction in overall cardiovascular risk with empagliflozin, liraglutide, and semaglutide treatment, respectively. Moreover, empagliflozin has become the first glucose-lowering agent indicated to reduce the risk of cardiovascular death in adults with T2DM and established cardiovascular disease. Results from cardiovascular outcomes trials have prompted an update to the 2017 American Diabetes Association standards of care, which now recommend consideration of empagliflozin or liraglutide for patients with suboptimally controlled long-standing T2DM and established atherosclerotic cardiovascular disease because these agents have been shown to reduce cardiovascular and all-cause mortality when added to standard care.

Introduction: This trial assessed safety and effectiveness of an advanced hybrid closedloop (AHCL) system with automated basal (Auto Basal) and automated bolus correction (Auto Correction) in adolescents and adults with type 1 diabetes (T1D). Materials and Methods:This multi-center, single-arm study involved an intent to treat population of 157 individuals (39 adolescents aged 14-21 years and 118 adults aged ≥22-75 years) with T1D. Study participants used the MiniMed™ AHCL system during a baseline run-in period in which sensor-augmented pump +/-predictive low glucose management or Auto Basal was enabled for ~14 days. Thereafter, Auto Basal and Auto Correction were enabled for a study phase (~90 days), with glucose target set to 100mg/dL or 120mg/dL for ~45 days, followed by the other target for ~45 days. Study endpoints included safety events and change in mean A1C, time in range (TIR, 70-180mg/dL) and time below range (TBR, <70mg/dL). Run-in and study phase values were compared using Wilcoxon signedrank test a or paired t-test.Results: Overall group time spent in closed loop averaged 94.9±5.4% and involved only 1.2±0.8 exits/week. Compared to run-in, AHCL reduced A1C from 7.5±0.8% to 7.0±0.5% (<0.001 a , N=155), TIR increased from 68.8±10.5% to 74.5±6.9% (<0.001 a ) and TBR reduced from 3.3±2.9% to 2.3±1.7% (<0.001 a ). Similar benefits to glycemia were observed for each age group, and were more pronounced for the nighttime (12AM-6AM). The 100mg/dL target increased TIR to 75.4% (N=155), that was further optimized at a lower active insulin time setting (i.e. 2 hours), without increasing TBR. There were no severe hypoglycemia or diabetic ketoacidosis events during the study phase.Conclusions: These findings show that the MiniMed™ AHCL system is safe and allows for achievement of recommended glycemic targets in adolescents and adults with T1D.Adjustments in target and active insulin time settings may further optimize glycemia and improve user experience. a Wilcoxon signed-rank test.