OBJECTIVEThe 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 METHODSPatients on stable metformin ( ‡1,500 mg/day) for ‡8 weeks with glycated hemoglobin (HbA 1c ) 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 (HbA 1c 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 HbA 1c from baseline to week 24. RESULTSThere was a significantly greater reduction in HbA 1c at 24 weeks with saxagliptin add-on (-0.51% [-5.6 mmol/mol]) versus placebo (-0.16% [-1.7 mmol/mol]) addon 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 HbA 1c <7% (53 mmol/mol) with saxagliptin add-on (35.3%) versus placebo add-on (23.1%) to dapagliflozin plus metformin. Adverse events were similar between treatment groups. Episodes of hypoglycemia were infrequent in both treatment arms, and there were no episodes of major hypoglycemia. CONCLUSIONSTriple therapy with the addition of saxagliptin to dapagliflozin plus metformin was well tolerated and produced significant improvements in HbA 1c in patients with type 2 diabetes inadequately controlled with dapagliflozin plus metformin.

IntroductionTo 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.MethodsDuring 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.ResultsMean 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 < 7.0% in study 1 and 17.5% in study 2. Dual therapy was well tolerated, with hypoglycemia incidence < 1% in both studies.ConclusionDual therapy improved glycemic control and was well tolerated; however, most patients required additional therapy to further improve HbA1c towards target, suggesting that an early move to triple therapy with oral glucose-lowering drugs rather than a stepwise approach may be beneficial for patients with high HbA1c levels on metformin therapy.Trial RegistrationClinicalTrials.gov NCT01619059, NCT01646320.FundingAstraZeneca.Electronic supplementary materialThe online version of this article (10.1007/s13300-018-0445-x) contains supplementary material, which is available to authorized users.

No abstract

Comparative study of isocnzymic patterns of acid phosphatase, β‐glucuronidase and α‐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 β‐glucuronidase of leukaemic cells were similar to that of normal lymphocytes. However, different patterns were found in the case of α‐naphthyl acetate esterase. Two prominent anodal bands were present in CLL lymphocytes; these bands were either absent or very weak in normal cells.

No abstract