The American Diabetes Association, JDRF, the European Association for the Study of Diabetes, and the American Association of Clinical Endocrinologists convened a research symposium, “The Differentiation of Diabetes by Pathophysiology, Natural History and Prognosis” on 10–12 October 2015. International experts in genetics, immunology, metabolism, endocrinology, and systems biology discussed genetic and environmental determinants of type 1 and type 2 diabetes risk and progression, as well as complications. The participants debated how to determine appropriate therapeutic approaches based on disease pathophysiology and stage and defined remaining research gaps hindering a personalized medical approach for diabetes to drive the field to address these gaps. The authors recommend a structure for data stratification to define the phenotypes and genotypes of subtypes of diabetes that will facilitate individualized treatment.

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.

Aim:Two treatment strategies were compared in patients with type 2 diabetes (T2DM) on basal insulin requiring intensification: addition of once-daily (OD) liraglutide (Lira) or OD insulin aspart (IAsp) with largest meal.Methods: Subjects completing 104 weeks (52-week main trial BEGIN ONCE-LONG + 52-week extension) on insulin degludec (IDeg) OD + metformin with HbA1c ≥ 7.0% (≥53 mmol/mol) were randomized to IDeg+Lira [n = 88, mean HbA1c: 7.7% (61 mmol/mol)] or IDeg+IAsp (n = 89, mean HbA1c: 7.7%) for 26 weeks, continuing metformin. Subjects completing 104 weeks with HbA1c <7.0% continued IDeg + metformin in a third, non-randomized arm (n = 236).Results: IDeg+Lira reduced HbA1c (−0.74%-points) significantly more than IDeg+IAsp (−0.39%-points); estimated treatment difference (ETD) (IDeg+Lira−IDeg+IAsp) −0.32%-points (95% CI −0.53; −0.12); p = 0.0024. More IDeg+Lira (49.4%) than IDeg+IAsp (7.2%) subjects achieved HbA1c <7.0% without confirmed hypoglycaemia [plasma glucose <3.1 mmol/l (<56 mg/dl) or severe hypoglycaemia) and without weight gain; estimated odds ratio (IDeg+Lira/IDeg+IAsp) 13.79 (95% CI 5.24; 36.28); p < 0.0001. IDeg+Lira subjects had significantly less confirmed and nocturnal confirmed hypoglycaemia, and significantly greater weight loss (−2.8 kg) versus IDeg+IAsp (+0.9 kg); ETD (IDeg+Lira−IDeg+IAsp) −3.75 kg (95% CI −4.70; −2.79); p < 0.0001. Other than more gastrointestinal side effects with IDeg+Lira, no safety differences occurred. Durability of IDeg was established in the non-randomized arm, as mean HbA1c remained <7.0% [mean 6.5% (48 mmol/mol) at end-of-trial].Conclusions: IDeg+Lira improved long-term glycaemic control, with weight loss and less hypoglycaemia versus adding a single daily dose of IAsp in patients with T2DM inadequately controlled with IDeg + metformin.