To evaluate the safety and efficacy of empagliflozin 10-and 25-mg doses plus a unique lower dose (2.5 mg) as adjunct to intensified insulin in patients with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS The EASE (Empagliflozin as Adjunctive to inSulin thErapy) program (N = 1,707) included two double-blind, placebo-controlled phase 3 trials: EASE-2 with empagliflozin 10 mg (n = 243), 25 mg (n = 244), and placebo (n = 243), 52-week treatment; and EASE-3 with empagliflozin 2.5 mg (n = 241), 10 mg (n = 248), 25 mg (n = 245), and placebo (n = 241), 26-week treatment. Together they evaluated empagliflozin 10 mg and 25 mg, doses currently approved in treatment of type 2 diabetes, and additionally 2.5 mg on 26-week change in glycated hemoglobin (primary end point) and weight, glucose time-in-range (>70 to £180 mg/dL), insulin dose, blood pressure, and hypoglycemia. RESULTS The observed largest mean placebo-subtracted glycated hemoglobin reductions

In the nervous system, NMDA receptors (NMDARs) participate in neurotransmission and modulate the viability of neurons. In contrast, little is known about the role of NMDARs in pancreatic islets and the insulin-secreting beta cells whose functional impairment contributes to diabetes mellitus. Here we found that inhibition of NMDARs in mouse and human islets enhanced their glucose-stimulated insulin secretion (GSIS) and survival of islet cells. Further, NMDAR inhibition prolonged the amount of time that glucose-stimulated beta cells spent in a depolarized state with high cytosolic Ca(2+) concentrations. We also noticed that, in vivo, the NMDAR antagonist dextromethorphan (DXM) enhanced glucose tolerance in mice, and that in vitro dextrorphan, the main metabolite of DXM, amplified the stimulatory effect of exendin-4 on GSIS. In a mouse model of type 2 diabetes mellitus (T2DM), long-term treatment with DXM improved islet insulin content, islet cell mass and blood glucose control. Further, in a small clinical trial we found that individuals with T2DM treated with DXM showed enhanced serum insulin concentrations and glucose tolerance. Our data highlight the possibility that antagonists of NMDARs may provide a useful adjunct treatment for diabetes.

ObjectivesTo summarise incidence and prevalence of diabetic ketoacidosis (DKA) in adults with type 1 diabetes (T1D) for the overall patient population and different subgroups (age, sex, geographical region, ethnicity and type of insulin administration).DesignSystematic literature review (SLR).Data sourcesMedline (via PubMed) and Embase (1 January 2000 to 23 June 2016).Study selectionPeer-reviewed observational studies with reported data on the incidence or prevalence of DKA in T1D adults were included. A single reviewer completed the study screening and selection process and a second reviewer performed an additional screening of approximately 20% of the publications; two reviewers independently conducted the quality assessment; the results were narratively synthesised.ResultsOut of 1082 articles, 19 met the inclusion and exclusion criteria, with two additional studies identified that did not specify the patient age range and are therefore not included in the SLR. Overall, eight studies reported incidence with a range of 0–56 per 1000 person-years (PYs), with one outlying study reporting an incidence of 263 per 1000 PYs. Eleven studies reported prevalence with a range of 0–128 per 1000 people. Prevalence of DKA decreased with increasing age. Subgroup analyses were performed using data from no more than two studies per subgroup. There was a higher prevalence of DKA reported in women, non-whites and patients treated with insulin injections compared with men, whites and patients using continuous subcutaneous insulin infusion pumps, respectively.ConclusionsTo our knowledge, this is the first SLR on the epidemiology of DKA in T1D adults. Despite an increasing prevalence of T1D in recent years, DKA in adults has been poorly characterised. In an era when the benefit–risk profiles of new antidiabetic therapies are being evaluated, including the potential risk of DKA, there is a clear need to better elucidate the expected rate of DKA among T1D adults.

BackgroundUp to now, only limited data on long-term medical treatment in congenital hyperinsulinism (CHI) is available. Moreover, most of the drugs used in CHI are therefore not approved. We aimed to assemble more objective information on medical treatment in CHI with regard to type and duration, dosage as well as side effects.MethodsWe searched MEDLINE (from 1947) and EMBASE (from 1988) using the OVID interface for relevant data to evaluate medical treatment in a large cohort of patients with CHI from different clinical centers. Randomized, controlled trials were not available. We evaluated case reports and case series. No language restrictions were made.ResultsA total number of 619 patients were medically treated and information regarding conservative treatment was available. Drugs used were diazoxide (in 84 % of patients), somatostatin analogues (16 %), calcium channel antagonists (4 %) and glucagon (1 %). Mean dose of diazoxide was 12.5 (±4.3) mg/kg ⋅ d (range 2–60 mg/kg ⋅ d), mean duration of diazoxide treatment until remission was 57 months. Side effects of diazoxide were usually not severe. The causal relation between diazoxide and severe side effects, e.g. heart failure (3.7 %) remains doubtful. Mean dose of octreotide was 14.9 (±7.5) μg/kg ⋅ d (range 2.3–50 μg/kg ⋅ d), of lanreotide 67.3 (±39.8) mg ⋅ month (range 10–120 mg ⋅ month). Mean duration of treatment with somatostatin analogues until remission was 49 months. Frequent side effects included tachyphylaxis and mild gastrointestinal symptoms. The risk of persistent growth deceleration was low (<5 %).ConclusionsSevere side effects are rare and a causal relation remains disputable. We conclude that long-term conservative treatment of CHI is feasible.