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Introduction To examine the utility of sequential versus dual add-on approaches in patients who have type 2 diabetes and inadequate glycemic control with metformin therapy alone, we characterized the efficacy and safety of dual therapy with dapagliflozin or saxagliptin added to metformin in the open-label lead-in periods of two phase 3 trials (study 1, NCT01619059; study 2, NCT01646320) that evaluated triple therapy in patients with inadequately controlled type 2 diabetes. Methods During the lead-in periods of each trial, patients [glycated hemoglobin (HbA1c) 8.0–11.5%] who had been receiving metformin ≥ 1500 mg/day for ≥ 8 weeks received metformin immediate release at an equivalent dose plus dapagliflozin 10 mg/day (study 1; N = 482) or saxagliptin 5 mg/day (study 2; N = 349) for 16 weeks. Efficacy end points were assessed at week − 2 before randomization. Results Mean change in HbA1c [95% confidence interval (CI)] from lead-in baseline (study 1, 9.3%; study 2, 9.4%) was − 1.6% (− 1.7, − 1.5) in study 1 and − 1.3% (− 1.5, − 1.2) in study 2. Mean changes (95% CI) from lead-in baseline in weight and fasting plasma glucose were − 2.4 kg (− 2.6, − 2.1) and − 47.5 mg/dL (− 52.8, − 42.3) for study 1 and − 0.5 kg (− 0.8, − 0.2) and − 28.5 mg/dL (− 35.8, − 21.2) for study 2. At the end of the lead-in period, 22.0% of patients achieved HbA1c

Comparative study of isoenzymic patterns of acid phosphatase, beta-glucuronidase and alpha-naphthyl acetate esterase of normal and chronic lymphocytic leukaemia (CLL) lymphocytes was carried out by means of polyacrylamide gel electrophoresis. The isoenzymograms of acid phosphatase and beta-glucuronidase of leukaemic cells were similar to that of normal lymphocytes. However, different patterns were found in the case of alpha-naphthyl acetate esterase. Two prominent anodal bands were present in CLL lymphocytes; these bands were either absent or very weak in normal cells.

OBJECTIVE The objective of this study was to assess the efficacy and safety of triple therapy with saxagliptin add-on versus placebo add-on to dapagliflozin plus metformin in adults with type 2 diabetes. RESEARCH DESIGN AND METHODS Patients on stable metformin (≥1,500 mg/day) for ≥8 weeks with glycated hemoglobin (HbA1c) 8.0–11.5% (64–102 mmol/mol) at screening received open-label dapagliflozin (10 mg/day) plus metformin immediate release (IR) for 16 weeks. Patients with inadequate glycemic control (HbA1c 7–10.5% [53–91 mmol/mol]) were then randomized to receive placebo (n = 153) or saxagliptin 5 mg/day (n = 162) in addition to background dapagliflozin plus metformin IR. The primary efficacy end point was change in HbA1c from baseline to week 24. RESULTS There was a significantly greater reduction in HbA1c at 24 weeks with saxagliptin add-on (–0.51% [–5.6 mmol/mol]) versus placebo (–0.16% [–1.7 mmol/mol]) add-on to dapagliflozin plus metformin (difference, –0.35% [95% CI –0.52% to –0.18%] and –3.8 [–5.7 to –2.0 mmol/mol], respectively; P < 0.0001). Reductions in fasting plasma glucose and 2-h postprandial glucose were similar between treatment arms. A larger proportion of patients achieved HbA1c CONCLUSIONS Triple therapy with the addition of saxagliptin to dapagliflozin plus metformin was well tolerated and produced significant improvements in HbA1c in patients with type 2 diabetes inadequately controlled with dapagliflozin plus metformin.