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Aims The efficacy and safety of sodium–glucose linked transporters (SGLT2s) plus metformin and a sulfonylurea (MET?+?SU) for the treatment of type 2 diabetes mellitus (T2DM) in patients who fail to achieve glycemic control with MET?+?SU, relative to other triple therapies licensed in the EU, were estimated.

Methods A systematic literature review and network meta-analysis (NMA) of randomized controlled trials (RCTs) involving anti-diabetes treatments added to MET?+?SU were conducted.

Results: Of 2236 abstracts identified through a systematic literature review, 30 RCTs published between 2003 and 2013 were included. RCTs ranged from 12 to 52 weeks in duration, included 28 to 1274 patients, were of parallel design, and most were open-label. Comparators included placebo (reference treatment), SGLT2 inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, thiazolidinediones (TZDs), alpha-glucosidase inhibitors (AGIs), meglitinides, glucagon-like peptide 1 (GLP-1) analogues, and basal, bolus, and biphasic insulin, all added on to MET?+?SU, as well as basal and biphasic insulin added to MET and monotherapy. The mean change (%) in HbA1c levels compared to placebo was -0.86 for SGLT2 inhibitors, ?0.68 for DPP-4 inhibitors, ?0.93 for TZDs, and ?1.07 for GLP-1 analogues, respectively. Only SGLT2 inhibitors and GLP-1 analogues led to a weight loss (?1.71 kg and ?1.14 kg, respectively) and decrease in systolic blood pressure (SBP; ?3.73 mmHg and ?2.90 mmHg, respectively), while all other treatments showed either an increase or no changes in weight or SBP.

Conclusion SGLT2 inhibitors are at least as effective as other classes of antidiabetic agents at controlling HbA1c levels, while providing the additional benefits of weight loss and reducing SBP. Additionally, since the risk of hypoglycemia is similar or reduced with SGLT2 inhibitors, patients do not have to trade off efficacy for tolerability. Similar findings were observed for GLP-1 analogues.  相似文献   
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BackgroundNational Institute for Health and Clinical Excellence guidelines (CG87) recommend neutral protamine hagedorn (NPH) insulin for the provision of basal insulin in type 2 diabetes, but use of analogue insulin is as much as 40%. Where residual endogenous insulin secretory capacity is present there is no evidence that analogue insulins provide any additional benefit over human insulins, and they come at an expensive premium. Anecdotally, however, there is a reluctance to switch people back to NPH insulin, partly because of a perceived risk of pancreatic failure and potential ketosis. Urinary C-peptide creatinine ratio (UCPCR) has been validated as a method for evaluating residual endogenous insulin secretion in type 1 and type 2 diabetes, with a UCPCR of no more than 0·2 nmol/mmol suggestive of absolute insulin deficiency. We aimed to evaluate the prevalence of true insulin deficiency among patients with type 2 diabetes with UCPCR, and confirm findings with the gold standard mixed meal tolerance test (MMTT).Methods191 insulin-treated patients with a clinical diagnosis of type 2 diabetes (diagnosed at or after age 45 years and who did not start insulin within the first year of diagnosis) collected a 2-h post-prandial urine sample for UCPCR measurement. Nine patients from two subgroups (UCPCR ≤0·2 nmol/mmol and UCPCR >0·2) completed a standard MMTT.Findings11 (5·8%) of 191 patients had two consistent UCPCRs of less than or equal to 0·2 nmol/mmol. Nine were able to do the MMTT, of whom five were confirmed to have absolute insulin deficiency (stimulated serum c-peptide <0·2 nmol/L). Three of these five patients were glutamic acid decarboxylase antibody-negative. Nine of nine patients with UCPCR of more than 0·2 nmol/L had confirmed endogenous insulin secretion in their MMTT. Those with insulin deficiency had a shorter time to starting insulin (median 2·5 years [IQR 1·5–3·0] vs 6·0 [3·0–10·75], p=0·005) and lower body-mass index (25 kg/m2 vs 29, p=0·04) but no other significant differences in clinical characteristics.InterpretationWe have demonstrated a very low prevalence of true pancreatic failure in this population of insulin-treated patients with type 2 diabetes. This requires further exploration by comparison of a population being treated with NPH insulin with one on analogue insulin, and then determining whether UCPCR could act as a clinical decision support tool to safely switch from analogue insulin to NPH insulin.FundingNational Institute for Health Research.  相似文献   
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急性淋巴细胞白血病(上)   总被引:2,自引:0,他引:2  
急性淋巴细胞白血病是淋巴前体细胞异常引起的恶性疾病,儿童与成人均可能发生。儿童发病高峰2~5岁。有效治疗的稳步进展使本病在儿童中的治愈率80%以上,同时为新的治疗方案提供了良机,新方案将保留我们在白血病无病生存病例中获得的治疗经验,同时减轻当前强化治疗方案中的毒副作用。  相似文献   
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