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Early systematic reviews or pooled analyses of randomized control trials suggested a neutral effect of sitagliptin [Engel et al. 2013], vildagliptin [Schweizer et al. 2010] and alogliptin [White et al. 2013b] on cardiovascular outcomes. Some meta-analyses even suggested a probable decrease in cardiovascular adverse events associated with saxagliptin [Frederich et al. 2010] and linagliptin [Johansen et al. 2012], or dipeptidyl peptidase-4 (DPP-4) inhibitors as a drug class [Monami et al. 2013]. However, these analyses were based mainly on studies of short duration and did not incorporate data from recently published dedicated cardiovascular safety trials [Karagiannis et al. 2014]. We provide an update on the effect of DPP-4 inhibitors on major adverse cardiovascular events (MACE) and the incidence of heart failure, based on recently published results from long-term clinical trials of sitagliptin [Green et al. 2015], saxagliptin [Scirica et al. 2013] and alogliptin [White et al. 2013a], and relevant updated meta-analyses in light of recent findings supporting a cardiovascular benefit for novel glucose lowering drugs in patients at high cardiovascular risk [Zinman et al. 2015]. Following concerns about the uncertainty regarding the cardiovascular profile of glucose lowering agents [Matthews and Tsapas, 2008], regulatory agencies in both Europe and the United States issued guidance requesting the assessment of cardiovascular safety of new antidiabetic medications during the early stages of their marketing authorization [FDA, 2008; CHMP, 2012]. The SAVOR-TIMI-53 [Scirica et al. 2013] and EXAMINE [White et al. 2013a] trials assessed the cardiovascular safety of saxagliptin and alogliptin, respectively. Both studies suggested a neutral effect on a 3-point MACE composite outcome of cardiovascular death, myocardial infarction or ischemic stroke. Similarly, the TECOS trial assessed the effect of sitagliptin on cardiovascular outcomes in 14,671 patients with type 2 diabetes and established cardiovascular disease [Green et al. 2015]. Sitagliptin was noninferior to placebo both for a 3-point [hazard ratio (HR) 0.99; 95% confidence interval (CI) 0.89–1.10) and a 4-point (HR 0.98; 95% CI 0.89–1.08) MACE composite outcome (including cardiovascular death, nonfatal myocardial infarction, nonfatal stroke and hospitalization for unstable angina). A conclusive answer about the cardiovascular safety of linagliptin is still pending the completion of two relevant long-term trials [ClinicalTrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT01897532","term_id":"NCT01897532"}}NCT01897532] [Marx et al. 2015]. Similarly to individual trial findings, a meta-analysis that estimated the effect of DPP-4 inhibitors on cardiovascular outcomes based on data from 50 randomized controlled trials with a minimum follow up of 24 weeks concluded that cardiovascular mortality [relative risk (RR) 0.97; 95% CI 0.85–1.11) and incidence of acute coronary syndrome (RR 0.97; 95% CI 0.87–1.08) or stroke (RR 0.98; 95% CI 0.81–1.18) did not differ between DPP-4 inhibitors and comparators [Wu et al. 2014]. Likewise, in a meta-analysis of 94 trials, treatment with DPP-4 inhibitors did not affect cardiovascular mortality and incidence of stroke [Savarese et al. 2015]. Interestingly though, the risk of myocardial infarction was reduced with DPP-4 inhibitors in the short, but not in the long term (duration of treatment ⩾29 weeks) [Savarese et al. 2015]. Finally, updated meta-analyses of individual DPP-4 inhibitors also support that neither vildagliptin (RR 0.82; 95% CI 0.61–1.11) [McInnes et al. 2015] nor linagliptin (HR 0.78; 95% CI 0.55–1.12) [Rosenstock et al. 2015] are associated with an increased risk for a composite outcome of adjudicated MACE relative to comparators. Despite the reassuring evidence from randomized controlled trials and meta-analyses about the overall cardiovascular profile of DPP-4 inhibitors, safety concerns have been raised regarding a potential risk for hospitalization for heart failure, as demonstrated for saxagliptin in the SAVOR-TIMI-53 study [Scirica et al. 2013]. Following this unexpected finding of a 27% increased RR of hospitalization for heart failure in patients assigned to saxagliptin, the US Food and Drug Administration (FDA) requested additional data to investigate a possible association between use of saxagliptin and heart failure [FDA, 2014]. Upon further examination of clinical trial data, the manufacturer concluded that the observed risk was more prominent in patients with chronic kidney disease, previous heart failure and elevated levels of natriuretic peptides [Scirica et al. 2014]. Subsequently, in April 2015, the FDA Advisory Committee almost unanimously concluded that saxagliptin has an acceptable cardiovascular risk profile, but recommended the addition of new safety information to the product’s labeling [AstraZeneca, 2015]. Unlike saxagliptin, rates of hospital admission for heart failure for sitagliptin (HR 1.00; 95% 0.83–1.20) [Green et al. 2015] and alogliptin (HR 1.07; 95% 0.79–1.46) [Zannad et al. 2015] were similar to placebo. In addition, treatment with alogliptin had a neutral effect on a composite outcome of hospitalization due to heart failure and cardiovascular death (HR 1.00; 95% 0.82–1.21) [Zannad et al. 2015]. Furthermore, recent meta-analyses of individual DPP-4 inhibitors do not associate either vildagliptin or linagliptin with increased risk for heart failure. In a meta-analysis of 40 trials with vildagliptin, incidence of adjudicated events of heart failure requiring hospitalization or new onset of heart failure did not differ between vildagliptin and comparator (RR 1.08; 95% 0.60–1.70) [McInnes et al. 2015]. Similarly, in a meta-analysis of 19, mainly placebo-controlled, studies, the risk for hospitalization for congestive heart failure was similar for linagliptin and the control group (HR 1.04; 95% CI 0.43–2.47) [Rosenstock et al. 2015]. Conversely, meta-analyses assessing all DPP-4 inhibitors as a drug class suggest that they are indeed associated with an increased risk for acute heart failure [Monami et al. 2014; Udell et al. 2015], heart failure hospitalization [Wu et al. 2014] or new heart failure onset [Savarese et al. 2015]. However, it should be noted that these findings are mainly driven by the results of the SAVOR-TIMI-53 and EXAMINE trials. Indeed, in the meta-analysis by Savarese and colleagues, a sensitivity analysis according to the type of DPP-4 inhibitor demonstrated an elevated risk of new heart failure onset only with saxagliptin (RR 1.20; 95% 1.01–1.41 ) and not with sitagliptin, vildagliptin, linagliptin or alogliptin [Savarese et al. 2015]. In conclusion, DPP-4 inhibitors do not seem to have any effect on major adverse cardiovascular outcomes and risk for heart failure, apart from saxagliptin which was associated with an increased risk for hospitalization for heart failure, predominantly in patients with chronic kidney disease, pre-existing heart failure or elevated baseline levels of natriuretic peptides. This neutral effect has been considered sufficient for the marketing approval of glucose lowering therapies by the FDA and the European Medicines Agency (EMA). However, publication of the EMPA-REG OUTCOME trial results for empagliflozin, a novel sodium glucose cotransporter 2 inhibitor, which demonstrated a highly beneficial effect on overall mortality and cardiovascular outcomes [Zinman et al. 2015], further undermines the clinical importance of data for surrogate outcomes and supports the need for use of hard, patient-important cardiovascular outcomes to guide therapeutic decision-making in diabetes.

Objectives An overview of systematic reviews (OoSRs) is a study designed to synthesize multiple evidence from existing systematic reviews on a specific domain. The aim of this paper was to offer a pilot version checklist with Preferred Reporting Items for OoSRs (PRIO-harms) to promote a more balanced reporting of benefits and harms in OoSRs of health care interventions. Study Design and Setting The included items were developed by combining key features from health care OoSRs designs with recommendations from statements of other relevant checklists and pertinent methodological review articles. Two raters independently used the PRIO-harms checklist to assess a sample of 20 OoSRs. Results The PRIO-harms tool consists of a 27-item (56 (sub-)items in total) checklist and is accompanied by a five-stage process flow diagram (identification, screening, eligibility, inclusion, and separation of relevant studies). The mean interrater reliability (Gwet's AC1 statistic) between reviewers was 0.90 (95% confidence interval: 0.88, 0.92) indicating a very good agreement. Conclusion The PRIO-harms tool can be used in every OoSRs that addresses health care interventions. This instrument will assist overview authors to improve completeness and transparency of research reporting with emphasis on harms. However, it might benefit from critical review and further validation from experts and research teams that produce OoSRs.

Importance The potential role of the fecal immunochemical test (FIT) for screening patients at increased risk for colorectal cancer (CRC) has not yet been elucidated. Objective To assess the diagnostic accuracy of FIT for CRC or advanced neoplasia (AN) in asymptomatic patients at above-average risk. Data Sources MEDLINE, EMBASE, Cochrane Library, and gray literature sources through August 2016. Study Selection Diagnostic studies evaluating the accuracy of FIT for CRC or AN in patients with a personal or familial history of CRC using colonoscopy as the reference standard. Data Extraction and Synthesis Two authors (A.K. and P.P.) independently extracted data and evaluated study quality using the Quality Assessment of Diagnostic Accuracy Studies–2 tool, and evaluated the quality of the body of evidence by means of GRADE (Grading of Recommendations Assessment, Development, and Evaluation). Hierarchical models were used to synthesize available evidence. Main Outcomes and Measures The primary outcome was the diagnostic performance of FIT for detecting CRC or AN. Results We included 12 studies (6204 participants). Seven studies were deemed at high or unclear risk of bias. The average sensitivity of FIT for CRC was 93% (95% CI, 53%-99%), and the average specificity was 91% (95% CI, 89%-92%), yielding a positive likelihood ratio (LR+) of 10.30 (CI 7.7-13.9) and a negative likelihood ratio (LR−) of 0.08 (95% CI, 0.01-0.75) (GRADE: very low). The average sensitivity of FIT for AN was 48% (95% CI, 39%-57%); and the average specificity was 93% (95% CI, 91%-94%), yielding an LR+ of 6.55 (95% CI, 5.0-8.5) and an LR− of 0.57 (95% CI, 0.48-0.67) (GRADE: very low). Subgroup analyses indicated that FIT cutoff values between 15- and 25-μg/g feces provided the best combination of sensitivity and specificity for the diagnosis of CRC (93% and 94%, respectively). Quantitative and 1-sample FIT showed adequate test performance, but data on other FIT brands and multiple samples were insufficient. Conclusions and Relevance The FIT has high overall diagnostic accuracy for CRC but moderate accuracy for AN in patients at above-average personal or familial risk. Heterogeneity and wide confidence intervals limit the trustworthiness of our findings.

INTRODUCTION Deciding on an optimal medication choice for type 2 diabetes is often challenging, due to the increasing number of treatment options. Canagliflozin is a novel glucose-lowering agent belonging to sodium-glucose co-transporter 2 (SGLT2) inhibitors. AIM The aim of this study was to examine and summarize the evidence based on the efficacy, safety, and cost-effectiveness of canagliflozin for type 2 diabetes. EVIDENCE REVIEW Compared to placebo, canagliflozin 100 and 300 mg lower glycated hemoglobin (HbA1c) by ~0.6%-0.8%, respectively. Canagliflozin appears to be slightly more effective than dipeptidyl peptidase-4 (DPP-4) inhibitors in reducing HbA1c. It also has a favorable effect on body weight and blood pressure, both versus placebo and most active comparators. However, treatment with canagliflozin is associated with increased incidence of genital tract infections and osmotic diuresis-related adverse events. Based on short-term data, canagliflozin is not associated with increased risk for all-cause mortality and cardiovascular outcomes. Economic evaluation studies from various countries indicate that canagliflozin is a cost-effective option in dual- or triple-agent regimens. PLACE IN THERAPY As monotherapy, canagliflozin could be used in patients for whom metformin is contraindicated or not tolerated. For patients on background treatment with metformin, canagliflozin appears to be superior to sulfonylureas with respect to body weight, blood pressure and risk for hypoglycemia, and to DPP-4 inhibitors in terms of lowering HbA1c, body weight, and blood pressure. Canagliflozin also seems to be cost-effective compared with sulfonylureas and DPP-4 inhibitors as add-on to metformin monotherapy, and compared with DPP-4 inhibitors as add-on to metformin and sulfonylurea. CONCLUSION Current evidence on intermediate efficacy outcomes, short-term safety and cost-effectiveness support the use of canagliflozin in patients on background treatment with metformin. Robust long-term data regarding the effect of canagliflozin on cardiovascular endpoints will be available upon completion of the Canagliflozin Cardiovascular Assessment Study (CANVAS) trial.

Thomas Karagiannis,1 Eleni Bekiari,1 Apostolos Tsapas1,2 1Clinical Research and Evidence‑Based Medicine Unit, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece; 2Harris Manchester College, University of Oxford, Oxford, UnitedKingdom Introduction: Deciding on an optimal medication choice for type 2 diabetes is often challenging, due to the increasing number of treatment options. Canagliflozin is a novel glucose-lowering agent belonging to sodium–glucose co-transporter 2 (SGLT2) inhibitors. Aim: The aim of this study was to examine and summarize the evidence based on the efficacy, safety, and cost-effectiveness of canagliflozin for type 2 diabetes. Evidence review: Compared to placebo, canagliflozin 100 and 300 mg lower glycated hemoglobin (HbA1c) by ~0.6%–0.8%, respectively. Canagliflozin appears to be slightly more effective than dipeptidyl peptidase-4 (DPP-4) inhibitors in reducing HbA1c. It also has a favorable effect on body weight and blood pressure, both versus placebo and most active comparators. However, treatment with canagliflozin is associated with increased incidence of genital tract infections and osmotic diuresis-related adverse events. Based on short-term data, canagliflozin is not associated with increased risk for all-cause mortality and cardiovascular outcomes. Economic evaluation studies from various countries indicate that canagliflozin is a cost-effective option in dual- or triple-agent regimens. Place in therapy: As monotherapy, canagliflozin could be used in patients for whom metformin is contraindicated or not tolerated. For patients on background treatment with metformin, canagliflozin appears to be superior to sulfonylureas with respect to body weight, blood pressure and risk for hypoglycemia, and to DPP-4 inhibitors in terms of lowering HbA1c, body weight, and blood pressure. Canagliflozin also seems to be cost-effective compared with sulfonylureas and DPP-4 inhibitors as add-on to metformin monotherapy, and compared with DPP-4 inhibitors as add-on to metformin and sulfonylurea. Conclusion: Current evidence on intermediate efficacy outcomes, short-term safety and cost-effectiveness support the use of canagliflozin in patients on background treatment with metformin. Robust long-term data regarding the effect of canagliflozin on cardiovascular endpoints will be available upon completion of the Canagliflozin Cardiovascular Assessment Study (CANVAS) trial. Keywords: canagliflozin, type 2 diabetes mellitus, evidence-based review, efficacy, safety, cost-effectiveness, tolerability, cardiovascular outcomes

Objective To assess the efficacy of the Diabetes Medication Choice Decision Aid among patients with type 2 diabetes in Greece. Design Open-label cluster randomised controlled trial. Setting Primary and secondary care practices across Greece. Participants 5 sites allocated to the decision aid (n=101 patients) and 4 sites to control (n=103 patients). Intervention Clinicians and patients in the intervention arm used a decision aid, based on outcomes that both consider important when choosing among antihyperglycaemic medications. Patients in the control arm received usual care. Outcome measures The primary outcome was patient's level of decisional comfort after the initial clinical encounter. Secondary outcomes included patient's knowledge about type 2 diabetes and medications, and patient's and clinician's satisfaction. Adherence to prescribed antihyperglycaemic medication and change in glycated haemoglobin were assessed at 24 weeks. Results Patients in both arms had similar scores in overall decisional comfort (mean difference between the usual care and decision aid arms −6.9, 95% CI −21.5 to 7.7) and its subscales. Patients' knowledge was high in both arms (mean difference 2.3%, 95% CI −15.7% to 20.4%). Patients and clinicians in both groups were equally satisfied with the decision-making. No significant difference in medication adherence and glycaemic control was found across arms. Clinicians found the decision aid useful and reported that its integration in their daily routine was easy. Conclusions The decision aid was implemented and positively received in the clinical setting in Greece, in line with the patient-centred approach endorsed by current guidelines. However, this trial yielded imprecise results in terms of patient outcomes. Further research is needed to investigate the interaction between the patient and the clinician in order to clarify the association between the use of decision aids and implementation of shared decision-making. Trial registration number [NCT01861756][1]. Pre-results. [1]: https://clinicaltrials.gov/ct2/show/study/NCT01861756

Objectives We performed a systematic review and meta-regression analysis of randomized control trials to investigate the association between response to initial treatment and survival outcomes in patients with newly diagnosed multiple myeloma (MM). Methods Response outcomes included complete response (CR) and the combined outcome of CR or very good partial response (VGPR), while survival outcomes were overall survival (OS) and progression-free survival (PFS). We used random-effect meta-regression models and conducted sensitivity analyses based on definition of CR and study quality. Results Seventy-two trials were included in the systematic review, 63 of which contributed data in meta-regression analyses. There was no association between OS and CR in patients without autologous stem cell transplant (ASCT) (regression coefficient: .02, 95% confidence interval [CI] −0.06, 0.10), in patients undergoing ASCT (−.11, 95% CI −0.44, 0.22) and in trials comparing ASCT with non-ASCT patients (.04, 95% CI −0.29, 0.38). Similarly, OS did not correlate with the combined metric of CR or VGPR, and no association was evident between response outcomes and PFS. Sensitivity analyses yielded similar results. Conclusions This meta-regression analysis suggests that there is no association between conventional response outcomes and survival in patients with newly diagnosed MM.

Non-alcoholic fatty liver disease (NAFLD), the most common liver disease, is characterized by accumulation of fat (>5% of the liver tissue), in the absence of alcohol abuse or other chronic liver diseases. It is closely related to the epidemic of obesity, metabolic syndrome or type 2 diabetes mellitus (T2DM). NAFLD can cause liver inflammation and progress to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis or hepatocellular cancer (HCC). Nevertheless, cardiovascular disease (CVD) is the most common cause of death in NAFLD/NASH patients. Current guidelines suggest the use of pioglitazone both in patients with T2DM and in those without. The use of statins, though considered safe by the guidelines, have very limited use; only 10% in high CVD risk patients are on statins by tertiary centers in the US. There are data from several animal studies, 5 post hoc analyses of prospective long-term survival studies, and 5 rather small biopsy proven NASH studies, one at baseline and on at the end of the study. All these studies provide data for biochemical and histological improvement of NAFLD/NASH with statins and in the clinical studies large reductions in CVD events in comparison with those also on statins and normal liver. Ezetimibe was also reported to improve NAFLD. Drugs currently in clinical trials seem to have potential for slowing down the evolution of NAFLD and for reducing liver- and CVD-related morbidity and mortality, but it will take time before they are ready to be used in everyday clinical practice. The suggestion of this Expert Panel is that, pending forthcoming randomized clinical trials, physicians should consider using a PPARgamma agonist, such as pioglitazone, or, statin use in those with NAFLD/NASH at high CVD or HCC risk, alone and/or preferably in combination with each other or with ezetimibe, for the primary or secondary prevention of CVD, and the avoidance of cirrhosis, liver transplantation or HCC, bearing in mind that CVD is the main cause of death in NAFLD/NASH patients.

Non-alcoholic fatty liver disease (NAFLD), the most common liver disease, is characterized by accumulation of fat (> 5% of the liver tissue), in the absence of alcohol abuse or other chronic liver diseases. It is closely related to the epidemic of obesity, metabolic syndrome or type 2 diabetes mellitus (T2DM). NAFLD can cause liver inflammation and progress to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis or hepatocellular cancer (HCC). Nevertheless, cardiovascular disease (CVD) is the most common cause of death in NAFLD/NASH patients. Current guidelines suggest the use of pioglitazone both in patients with T2DM and in those without. The use of statins, though considered safe by the guidelines, have very limited use; only 10% in high CVD risk patients are on statins by tertiary centers in the US. There are data from several animal studies, 5 post hoc analyses of prospective long-term survival studies, and 5 rather small biopsy proven NASH studies, one at baseline and on at the end of the study. All these studies provide data for biochemical and histological improvement of NAFLD/NASH with statins and in the clinical studies large reductions in CVD events in comparison with those also on statins and normal liver. Ezetimibe was also reported to improve NAFLD. Drugs currently in clinical trials seem to have potential for slowing down the evolution of NAFLD and for reducing liver- and CVD-related morbidity and mortality, but it will take time before they are ready to be used in everyday clinical practice. The suggestion of this Expert Panel is that, pending forthcoming randomized clinical trials, physicians should consider using a PPARgamma agonist, such as pioglitazone, or, statin use in those with NAFLD/NASH at high CVD or HCC risk, alone and/or preferably in combination with each other or with ezetimibe, for the primary or secondary prevention of CVD, and the avoidance of cirrhosis, liver transplantation or HCC, bearing in mind that CVD is the main cause of death in NAFLD/NASH patients. © 2017 Elsevier Inc.

Objective: To assess the efficacy and safety of omarigliptin and trelagliptin, novel dipeptidyl peptidase-4 inhibitors administered once-weekly (DPP-4i QW). Methods: We systematically searched for placebo- and active-controlled randomized trials in adults with type 2 diabetes mellitus. Results: Fifteen primary studies with 5709 participants were included. DPP-4i QW were more effective than placebo in reducing hemoglobin A1c (HbA1c) (Weighted Mean Difference (WMD) −0.63%; 95% CI −0.80, −0.46; I2 = 84%) and had a similar glucose-lowering effect with daily DPP-4i (WMD 0.01%; −0.08, 0.11%; I2 = 34%). Omarigliptin was less effective compared with oral antidiabetic agents, other than daily DPP-4i, (WMD 0.24%; 0.10, 0.38; I2 = 12%). Omarigliptin did not affect body weight (WMD versus placebo 0.60 kg; 0.25, 0.96; I2 = 0%). Risk for any hypoglycemia was similar between DPP-4i QW and placebo (Odds Ratio 1.32; 0.78, 2.22; I2 = 0%). Incidence of other adverse events did not differ between DPP-4i QW and control. Conclusions: DPP-4i QW were superior to placebo and similar to daily DPP-4i in terms of glycemic control, and were not associated with any specific adverse events. There is limited comparative effectiveness evidence against other agents, while their effect on hard clinical safety outcomes is unknown.

Objective:Diabetic Kidney Disease is a serious microvascular complication of diabetes mellitus and the leading cause of end-stage-renal-disease in Western countries. New therapeutic agents are needed to delay its onset and progression. Recent literature suggests that sodium-glucose co-transporter 2

The affiliation details for Geltrude Mingrone are corrected below.

Objective To evaluate the quality of systematic reviews (SRs) affecting clinical practice in endocrinology. Study Design and Setting We identified all SRs cited in The Endocrine Society's Clinical Practice Guidelines published between 2006 and January 2012. We evaluated the methodological and reporting quality of the SRs in duplicate using the Assessment of Multiple Systematic Reviews (AMSTAR) tool. We also noted if the guidelines recommendations that are clearly supported by SRs acknowledged their quality. Results During the 5-year period of study, endocrine guidelines cited 69 SRs. These SRs had a mean AMSTAR score of 6.4 (standard deviation, 2.5) of a maximum score of 11, with scores improving over time. SRs of randomized trials had higher AMSTAR scores than those of observational studies. Low-quality SRs (methodological AMSTAR score 1 or 2 of 5, n = 24, 35%) were cited in 24 different recommendations and were the main evidentiary support for five recommendations, of which only one acknowledged the quality of SRs. Conclusion Few recommendations in endocrinology are supported by SRs. The quality of SRs is suboptimal and is not acknowledged by guideline developers.

Background The primary aim of this case-control study was to compare women whose pregnancy was complicated with gestational diabetes mellitus (GDM), diagnosed by the new International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria, with a control group of healthy, pregnant women in terms of incidence of large- (LGA) and small-for-gestational-age (SGA) neonates. Our secondary aim was to compare intrauterine growth of fetuses between the same 2 populations. Patients and methods The study included 289 women diagnosed as having GDM in the current pregnancy and 1 108 pregnant controls. Women were followed-up every 2 (GDM group) or 4 weeks (control group). The main metabolic parameters recorded were body mass index, fasting plasma glucose, home blood glucose and glycated hemoglobin A1c. The main ultrasonographic parameters were estimated fetal weight (EFW), head (HC) and abdominal circumferences (AC). Decisions on treatment modification in the GDM group were based on both metabolic and ultrasonographic parameters. Results There was no evidence for a difference in the incidence of LGA (9.9 vs. 9.2%, Chi-square, p=0.745) or SGA (10.5 vs. 9.0%, p=0.524) in GDM and in control group, respectively. No significant differences were found in EFW or AC between GDM and control groups during the second and third trimester. Conclusions Incidence of LGA and SGA neonates is similar among healthy pregnant women and women with GDM, diagnosed by the new IADPSG criteria and treated according to both metabolic and ultrasonographic parameters.

Deferasirox (DFRA) is a novel oral chelator agent for treatment of iron overload. Although well established in the treatment of β-thalassemia major (β-TM), it has not yet been fully investigated in patients with sickle cell disease. The aim of this report is to present the preliminary results of a pilot study assessing the effect of 4 years of DFRA treatment in six patients with sickle cell disease who are in need of recurrent transfusions. Our results show a significant reduction of ferritin levels and improvement of liver hemosiderosis, assessed by means of magnetic resonance imaging T2* (MRI T2*). None of the patients presented any serious adverse effects and the treatment was well tolerated. These results are in accordance with previous studies about the use of DFRA in sickle cell disease.

OBJECTIVE: To assess the efficacy and safety of dipeptidyl peptidase-4 (DPP-4) inhibitors compared with metformin as monotherapy, or with other commonly used hypoglycaemic drugs combined with metformin, in adults with type 2 diabetes mellitus. DESIGN: Systematic review and meta-analysis of randomised controlled trials. DATA SOURCES: Medline, Embase, the Cochrane Library, conference proceedings, trial registers, and drug manufacturers' websites. ELIGIBILITY CRITERIA: Randomised controlled trials of adults with type 2 diabetes mellitus that compared a DPP-4 with metformin as monotherapy or with a sulfonylurea, pioglitazone, a glucagon-like peptide-1 (GLP-1) agonist, or basal insulin combined with metformin on the change from baseline in glycated haemoglobin (HbA(1c)). DATA EXTRACTION: The primary outcome was the change in HbA(1c). Secondary outcomes included the proportion of patients achieving the goal of HbA(1c)

We read with interest the study by Konduracka et al. , 1 which concludes that patients with long-term type 1 diabetes mellitus under intensive insulin treatment do not have echocardiographic, biochemical, or morphological signs of diabetic cardiomyopathy. However, as the authors admit, this is directly opposed to several previous studies which clearly show the presence of myocardial diastolic dysfunction in patients with type 1 diabetes, when compared with control subjects.2–4 Importantly, like Konduracka et al. , these studies excluded patients with coronary artery disease and hypertension. These co-morbidities may themselves result in diastolic impairment, thus precluding any firm conclusions …

Background Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs. Purpose To assess the efficacy and safety of SGLT2 inhibitors in adults with type 2 diabetes. Data sources MEDLINE, EMBASE, and the Cochrane Library from inception through April 2013 without language restrictions; regulatory authorities' reports; and gray literature. Study selection Randomized trials comparing SGLT2 inhibitors with placebo or other medication for type 2 diabetes. Data extraction Three reviewers extracted or checked data for study characteristics, outcomes of interest, and risk of bias, and 3 reviewers summarized strength of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. Data synthesis Sodium-glucose cotransporter 2 inhibitors were compared with placebo in 45 studies (n = 11 232) and with active comparators in 13 studies (n = 5175). They had a favorable effect on hemoglobin A1c level (mean difference vs. placebo, -0.66% [95% CI, -0.73% to -0.58%]; mean difference vs. active comparators, -0.06% [CI, -0.18% to 0.05%]). Sensitivity analyses incorporating unpublished data showed similar effect estimates. Compared with other agents, SGLT2 inhibitors reduced body weight (mean difference, -1.80 kg [CI, -3.50 to -0.11 kg]) and systolic blood pressure (mean difference, -4.45 mm Hg [CI, -5.73 to -3.18 mm Hg]). Urinary and genital tract infections were more common with SGLT2 inhibitors (odds ratios, 1.42 [CI, 1.06 to 1.90] and 5.06 [CI, 3.44 to 7.45], respectively). Hypoglycemic risk was similar to that of other agents. Results for cardiovascular outcomes and death were inconclusive. An imbalance in incidence of bladder and breast cancer was noted with dapagliflozin compared with control. Limitation Most trials were rated as high risk of bias because of missing data and last-observation-carried-forward methods. Conclusion Sodium-glucose cotransporter 2 inhibitors may improve short-term outcomes in adults with type 2 diabetes, but effects on long-term outcomes and safety are unclear. Primary funding source None.