Summary Background The safety and effectiveness of a continuous, day-and-night automated glycaemic control system using insulin and glucagon has not been shown in a free-living, home-use setting. We aimed to assess whether bihormonal bionic pancreas initialised only with body mass can safely reduce mean glycaemia and hypoglycaemia in adults with type 1 diabetes who were living at home and participating in their normal daily routines without restrictions on diet or physical activity. Methods We did a random-order crossover study in volunteers at least 18 years old who had type 1 diabetes and lived within a 30 min drive of four sites in the USA. Participants were randomly assigned (1:1) in blocks of two using sequentially numbered sealed envelopes to glycaemic regulation with a bihormonal bionic pancreas or usual care (conventional or sensor-augmented insulin pump therapy) first, followed by the opposite intervention. Both study periods were 11 days in length, during which time participants continued all normal activities, including athletics and driving. The bionic pancreas was initialised with only the participant’s body mass. Autonomously adaptive dosing algorithms used data from a continuous glucose monitor to control subcutaneous delivery of insulin and glucagon. The coprimary outcomes were the mean glucose concentration and time with continuous glucose monitoring (CGM) glucose concentration less than 3·3 mmol/L, analysed over days 2–11 in participants who completed both periods of the study. This trial is registered with ClinicalTrials.gov, number NCT02092220. Findings We randomly assigned 43 participants between May 6, 2014, and July 3, 2015, 39 of whom completed the study: 20 who were assigned to bionic pancreas first and 19 who were assigned to the comparator first. The mean CGM glucose concentration was 7·8 mmol/L (SD 0·6) in the bionic pancreas period versus 9·0 mmol/L (1·6) in the comparator period (difference 1·1 mmol/L, 95% CI 0·7–1·6; p<0·0001), and the mean time with CGM glucose concentration less than 3·3 mmol/L was 0·6% (0·6) in the bionic pancreas period versus 1·9% (1·7) in the comparator period (difference 1·3%, 95% CI 0·8–1·8; p<0·0001). The mean nausea score on the Visual Analogue Scale (score 0–10) was greater during the bionic pancreas period (0·52 [SD 0·83]) than in the comparator period (0·05 [0·17]; difference 0·47, 95% CI 0·21–0·73; p=0·0024). Body mass and laboratory parameters did not differ between periods. There were no serious or unexpected adverse events in the bionic pancreas period of the study. Interpretation Relative to conventional and sensor-augmented insulin pump therapy, the bihormonal bionic pancreas, initialised only with participant weight, was able to achieve superior glycaemic regulation without the need for carbohydrate counting. Larger and longer studies are needed to establish the long-term benefits and risks of automated glycaemic management with a bihormonal bionic pancreas. Funding National Institute of Diabetes and Digestive and Kidney Diseases of the...

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Aim To compare the relative safety and effectiveness of bexagliflozin and sitagliptin as adjuncts to metformin for the treatment of adults with type 2 diabetes. Methods Participants (n = 386) were randomized to receive bexagliflozin (20 mg) or sitagliptin (100 mg) in addition to their existing doses of metformin. The primary endpoint was the non‐inferiority of bexagliflozin to sitagliptin for change in HbA1c from baseline to week 24. Changes from baseline to week 24 in fasting plasma glucose (FPG), body mass (in subjects with baseline body mass index ≥25 kg m−2) and systolic blood pressure (SBP) were secondary endpoints. Results The mean change from baseline to week 24 in HbA1c was −0.74 (95% CI −0.86%, −0.62%) in the bexagliflozin arm and −0.82% (95% CI −0.93%, −0.71%) in the sitagliptin arm, establishing non‐inferiority. The changes from baseline FPG, body mass and SBP were −1.82 mmol L−1, −3.35 kg and −4.23 mmHg in the bexagliflozin arm and −1.45 mmol L−1, −0.81 kg and −1.90 mmHg in the sitagliptin arm, respectively. These differences were significant for the first two measures (one‐sided P = 0.0123, P < 0.0001 and P = 0.0276, respectively.) Adverse events were experienced by 47.1% of subjects in the bexagliflozin arm and 56.0% of subjects taking sitagliptin. Serious adverse events affected 3.7% of subjects in the bexagliflozin arm and 2.1% of subjects in the sitagliptin arm. Conclusions Bexagliflozin was non‐inferior to sitagliptin and provided benefits over sitagliptin in FPG and body mass. Adverse event incidences in the two arms were similar.

Aim To compare the effects of bexagliflozin tablets 20 mg, with those of optimally titrated glimepiride when used to treat adults with type 2 diabetes mellitus (T2DM) inadequately controlled by metformin. Methods Adults with type 2 diabetes (n = 426) taking metformin, and with a glycated haemoglobin (HbA1c) level between 53 and 91 mmol/mol [7.0% and 10.5%], were randomized to receive bexagliflozin tablets 20 mg or titrated glimepiride. The primary endpoint was the intergroup difference in the change from baseline to Week 60 in percent HbA1c. Secondary endpoints included changes from baseline in body mass and systolic blood pressure (SBP), and proportion of subjects experiencing severe or documented symptomatic hypoglycaemia. Results The intergroup difference in percent HbA1c (bexagliflozin minus glimepiride) from baseline to Week 60 was −0.55 mmol/mol (95% confidence interval [CI] –2.30, 1.20)‐[−0.05% (−0.21, 0.11)], establishing noninferiority of bexagliflozin to glimepiride by the prespecified margin of 3.83 mmol/mol [0.35%]. Prespecified tests gave, in order, a difference in body mass of −4.31 kg (95% CI −5.10, −3.52; P < 0.0001), a difference in SBP of −6.53 mm Hg (95% CI −10.56, −2.51; P = 0.0008), and an odds ratio of 0.12 (95% CI 0.05, 0.28; P < 0.0001) for severe or documented symptomatic hypoglycaemia. At the follow‐up visit the mean difference in estimated glomerular filtration rate (eGFR) between arms was 6.05 mL min−1 per 1.73 m2 (95% CI, 3.24, 8.87; P < 0.0001). Conclusions Bexagliflozin was noninferior to glimepiride in lowering HbA1c, was superior to glimepiride for decreases in body mass and SBP, and was associated with significantly fewer hypoglycaemic events than glimepiride. A favourable effect on eGFR was observed.

ALTHEA ANAGNOSTOPOULOS, MS 2OBJECTIVE -To measure hematocrit (Hct) and glucose concentration in capillary blood drawn from the fingertip and forearm of a group of 50 nonfasting subjects with diabetes. RESEARCH DESIGN AND METHODS -Hct was determined indirectly by measuringHb with the HemoCue B-Hemoglobin Photometer. Glucose was assayed with the HemoCue B-Glucose Analyzer, chosen as the independent control assay, and the Sof-Tact Blood Glucose System. Testing session with each subject lasted ϳ30 min and consisted of a sequence of tests with each device (SofTact, HemoCue Glucose, and HemoCue Hemoglobin), performed on the arm and then on the fingertip. This sequence was performed three times, so all tests were done in triplicate. Additional fingersticks were performed on each subject at the start and end of the session to measure net change of glucose status during the experiment with a YSI Glucose Analyzer. The mean of the triplicate assays was used to calculate each subject's percent of glucose difference between arm and finger [(arm glucose Ϫ finger glucose)/finger glucose]. Because of the order in which replicates were performed, time-dependent changes in the glucose status of subjects had little effect on the mean values. Thus, the percent of glucose difference calculated herein reflects the intrinsic difference between forearm and fingertip.RESULTS -Hb concentration and Hct were found to be significantly higher in the arm than in the finger. When intraperson differences were calculated, the difference for Hb and Hct was found to be 1.8 Ϯ 1.1 g/dl (mean Ϯ SD) and 5.3 Ϯ 3.0%, respectively. In contrast to Hb, the percent of glucose difference between arm and finger was statistically insignificant. When measured with HemoCue, the percent of glucose difference was Ϫ0.1 Ϯ 8% for all 50 subjects, Ϫ1 Ϯ 6% for 20 subjects, for whom blood glucose varied Ͻ9 mg/dl during the experiment, and 2 Ϯ 10% for 15 subjects, for whom blood glucose varied Ͼ18 mg/dl. Thus, irrespective of how much blood glucose changed among the subjects, the glucose difference between forearm and fingertip was insignificant and less than measurement errors. A major source of error in the calculated differences was variability between replicates. No correlation was observed between an individual's Hct bias and his or her percent of glucose difference, as measured with HemoCue. The results with Sof-Tact were similar, with percent of glucose difference again being statistically insignificant. The measured difference was Ϫ4 Ϯ 13% for all 50 subjects, Ϫ1 Ϯ 15% for 20 subjects, for whom blood glucose varied Ͻ9 mg/dl during the experiment, and Ϫ1 Ϯ 12% for 15 subjects, for whom blood glucose varied Ͼ18 mg/dl. There was no correlation between a subject's Hct bias and his or her glucose difference, as measured with Sof-Tact.CONCLUSIONS -In this cross-sectional study of 50 nonfasting subjects whose blood glucose concentration changed to various degrees during the experiment, no significant glucose difference was observed between the capillary beds of the fore...