Oral glucose lowering with linagliptin and metformin compared with linagliptin alone as initial treatment in Asian patients with newly diagnosed type 2 diabetes and marked hyperglycemia: Subgroup analysis of a randomized clinical trial.

AIMS/INTRODUCTION: Type 2 diabetes mellitus is an epidemic in Asia, yet clinical trials of glucose-lowering therapies often enroll predominantly Western populations. We explored the initial combination of metformin and linagliptin, a dipeptidyl peptidase-4 inhibitor, in newly diagnosed type 2 diabetes mellitus patients in Asia with marked hyperglycemia. MATERIALS AND METHODS: This was a post-hoc subgroup analysis of a multinational, parallel-group clinical trial in which 316 newly diagnosed type 2 diabetes mellitus patients with glycated hemoglobin A1c (HbA1c) 8.5-12.0% were randomized to double-blind oral treatment with linagliptin/metformin or linagliptin monotherapy. The primary end-point was the change from baseline in HbA1c at week 24. We evaluated data for the 125 participants from Asian countries. RESULTS: After 24 weeks, the mean ± standard error reduction from baseline in HbA1c (mean 10.0%) was -2.99 ± 0.18% with linagliptin/metformin and -1.84 ± 0.18% with linagliptin; a treatment difference of -1.15% (95% confidence interval -1.65 to -0.66, P < 0.0001). HbA1c <7.0% was achieved by 60% of participants receiving linagliptin/metformin. The mean bodyweight change after 24 weeks was -0.45 ± 0.41 kg and 1.33 ± 0.45 kg in the linagliptin/metformin and linagliptin groups, respectively (treatment difference -1.78 kg [95% confidence interval -2.99 to -0.57, P = 0.0043]). Drug-related adverse events occurred in 9.7% of participants receiving linagliptin/metformin and 4.8% of those receiving linagliptin. Hypoglycemia occurred in 6.5% and 4.8% of the linagliptin/metformin and linagliptin groups, respectively, with no severe episodes. Gastrointestinal disorders occurred in 12.9% and 12.7% of the linagliptin/metformin and linagliptin groups, respectively, with no associated treatment discontinuations. CONCLUSIONS: In people from Asia with newly diagnosed type 2 diabetes mellitus and marked hyperglycemia, the initial combination of linagliptin and metformin substantially improved glycemic control without weight gain and with infrequent hypoglycemia. Initial oral combination therapy might be a viable treatment for such individuals.

Kinematic measures provide useful information after intracranial aneurysm treatment.

INTRODUCTION: Current methods of assessing the outcomes of intracranial aneurysm treatment for aneurysmal subarachnoid haemorrhage are relatively insensitive, and thus unlikely to detect subtle deficits. Failures to identify cognitive and motor outcomes of intracranial aneurysm treatment might prevent delivery of optimal post-operative care. There are also concerns over risks associated with using intracranial aneurysm treatment as a preventative measure. METHODS: We explored whether our kinematic tool would yield useful information regarding motor/cognitive function in patients who underwent intracranial aneurysm treatment for aneurysmal subarachnoid haemorrhage or unruptured aneurysm. Computerised kinematic motor and learning tasks were administered alongside standardised clinical outcome measures of cognition and functional ability, in 10 patients, as a pilot trial. Tests at post-intracranial aneurysm treatment discharge and six-week follow-up were compared to see which measures detected changes. RESULTS: Kinematic tests captured significant improvements from discharge to six-week follow-up, indexed by reduced motor errors and improved learning. Increased Addenbrooke's Cognitive Examination-Revised scores reflected some recovery of memory function for most individuals, but other standardised cognitive measures, functional outcome scores and a psychological questionnaire showed no changes. CONCLUSIONS: Kinematic measures can identify variation in performance in individuals with only slightly improved abilities post-intracranial aneurysm treatment. These measures may provide a sensitive way to explore post-operative outcomes following intracranial aneurysm treatment, or other similar surgical procedures.

Linagliptin plus metformin in patients with newly diagnosed type 2 diabetes and marked hyperglycemia.

OBJECTIVES: Few studies of oral glucose-lowering drugs exist in newly diagnosed type 2 diabetes (T2D) patients with marked hyperglycemia, and insulin is often proposed as initial treatment. We evaluated the oral initial combination of metformin and linagliptin, a dipeptidyl peptidase-4 inhibitor, in this population. METHODS: We performed a pre-specified subgroup analysis of a randomized study in which newly diagnosed T2D patients with glycated hemoglobin A1c (HbA1c) 8.5%-12.0% received linagliptin/metformin or linagliptin monotherapy. Subgroups of baseline HbA1c, age, body-mass index (BMI), renal function, race, and ethnicity were evaluated, with efficacy measured by HbA1c change from baseline after 24 weeks. RESULTS: HbA1c reductions from baseline (mean 9.7%) at week 24 in the overall population were an adjusted mean -2.81% ± 0.12% with linagliptin/metformin (n = 132) and -2.02% ± 0.13% with linagliptin (n = 113); treatment difference -0.79% (95% CI -1.13 to -0.46, P < 0.0001). In patients with baseline HbA1c ≥9.5%, HbA1c reduction was -3.37% with linagliptin/metformin (n = 76) and -2.53% with linagliptin (n = 61); difference -0.84% (95% CI -1.32 to -0.35). In those with baseline HbA1c <9.5%, HbA1c reduction was -2.08% with linagliptin/metformin (n = 56) and -1.39% with linagliptin (n = 52); difference -0.69% (95% CI -1.23 to -0.15). Changes in HbA1c and treatment differences between the linagliptin/metformin and linagliptin groups were of similar magnitudes to the overall population across patient subgroups based on age, BMI, renal function, and race. Drug-related adverse events occurred in 8.8% and 5.7% of linagliptin/metformin and linagliptin patients, respectively; no severe hypoglycemia occurred. CONCLUSION: Linagliptin/metformin combination in newly diagnosed T2D patients with marked hyperglycemia was well tolerated and elicited substantial improvements in glycemic control regardless of baseline HbA1c, age, BMI, renal function, or race. Thus, newly diagnosed, markedly hyperglycemic patients may be effectively treated by combinations of oral agents. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifier is NCT01512979.

WITHDRAWN: A Comparison of Internet Monitoring with Continuous Glucose Monitoring in Insulin-Requiring Type 2 Diabetes Mellitus.

OBJECTIVE: To compare the effects of real-time continuous glucose monitoring (RT-CGM) and an Internet blood glucose monitoring system (IBGMS) on glycated hemoglobin levels in patients with type 2 diabetes mellitus treated with insulin. METHODS: Fifty-seven patients with type 2 diabetes treated with insulin were assigned randomly to 1 of 2 groups. Group 1 had the results of their self-monitoring of blood glucose level monitored biweekly using an IBGMS. Group 2 used RT-CGM and were monitored biweekly. Both groups used a secure website to upload data and to receive feedback from their endocrinologist. A1C and laboratory test results were collected at 0, 3 and 6 months. RESULTS: The baseline parameters were not significantly different. After a 6-month follow-up period, both IBGMS and RT-CGM showed significant within-group improvements in A1C level. In the IBGMS group, the A1C level decreased from 8.79%±1.25% to 7.96%±1.30% (p<0.05). The RT-CGM group decreased from 8.80%±1.37% to 7.49%±0.70% (p<0.001). IBGMS and RT-CGM did not show significantly different A1C levels at baseline, 3 and 6 months (p>0.05). CONCLUSIONS: The use of both IBGMS and RT-CGM significantly improved A1C levels in patients with type 2 diabetes treated with insulin in a randomized trial over a 6-month period. There were no significant differences in A1C values between groups after 6 months.

Determining starting basal rates of insulin infusion for insulin pump users: a comparison between methods.

OBJECTIVE: We aimed to assess the accuracy and safety of presently available methods of estimating starting basal insulin rates for patients with type 1 and 2 diabetes, and to compare them against an empirically derived standard basal rate and a newly developed regression formula. RESEARCH DESIGN AND METHODS: Data on 61 patients with type 1 diabetes on continuous subcutaneous insulin infusion (CSII) therapy and 34 patients with type 2 diabetes on CSII were reviewed. Patient data were first analyzed for correlations between initial patient parameters and final basal rates. Starting basal rates were then retrospectively calculated for these patients according to the weight-based method (WB-M), the total daily dose (TDD) of insulin method (TDD-M), a flat empiric value, and a new formula developed by regression analysis of clinical data. These 4 methods were subsequently compared in their accuracy and potential risk of hypoglycemia. RESULTS: For type 1 diabetes, patient weight and TDD of long-acting insulin correlated with final basal rates. Both the regression formula and the TDD-M appeared safer than the WB-M and empirical estimates. For type 2 diabetes, only patient TDD of long-acting insulin correlated with final basal rates. The regression formula was significantly more accurate for patients with type 2 diabetes overall, but the TDD-M estimate was marginally safer. CONCLUSIONS: The pre-existing TDD-M was found to be the safest presently recommended estimate of initial basal rates for pump initiation in both type 1 and 2 diabetes. The best-fit regression was found to have potential use for type 2 CSII initiation.

The effectiveness of Internet intervention on 926 patients with diabetes mellitus for up to 30 months.

OBJECTIVE: To assess the long-term effect of an Internet blood glucose monitoring system (IBGMS) on patients with type 1 diabetes mellitus and patients with type 2 diabetes. METHODS: In all, 1200 patients were offered to be taught to communicate with their endocrinologists using standardized glucose level reports by e-mail, and received feedback within 24 hours. The first 926 patients enrolled were reviewed consecutively from March 2011 to October 2013. Seventy-seven of these patients were excluded owing to lack of glycated hemoglobin (A1C) data. The remaining 849 patients consisted of 295 patients with type 1 diabetes and 554 patients with type 2 diabetes. Nonreporters are patients with no record of reporting (n=167), whereas the reporters had reported at least once (n=682). The A1C values were obtained at registration; follow-up values at 3-month intervals were recommended. RESULTS: Reporter A1C decreased from 8.13%±1.34% to 7.74%±1.11% (p<0.0001). Reporters with type 1 diabetes dropped from 8.04%±1.23% to 7.72%±1.03% (n=238; p<0.0001). Reporters with type 2 diabetes dropped from 8.18%±1.40% to 7.75%±1.14% (n=444; p<0.0001) and were subdivided based on treatment: those on oral hypoglycemic agents declined from 7.96%±1.38% to 7.49%%±1.03% (p<0.0001), and those on insulin with or without oral hypoglycemic agents declined from 8.40%%±1.39% to 8.02%±1.20% (p<0.0001). The nonreporters did not show a significant change in A1C. CONCLUSIONS: Initial and prolonged improvement was found in A1C levels for all reporters. The data support that numerous patients can be followed up effectively using the Internet for as long as 30 months.

Internet blood glucose monitoring systems provide lasting glycemic benefit in type 1 and 2 diabetes: a systematic review.

Internet blood glucose monitoring systems (IBGMS) are associated with improved glycemic control in patients with type 2 diabetes (T2D) who are pharmacologically managed, using oral agents or insulin. IBGMS improves glycemic levels in patients with type 1 diabetes (T1D). IBGMS has not led to increased hypoglycemia. Mechanisms underlying IBGMS-associated glycemic improvement extend beyond optimizing insulin dose titration. The most important effects seem to be associated with increased patient self-motivation and improved patient-physician communication. IBGMS have been recommended in clinical practice guidelines, and their effectiveness and safety in trials suggest that this approach is appropriate for patients with T1D or T2D.

A multiplicity of targets: evaluating composite endpoint studies of the GLP-1 receptor agonists in type 2 diabetes.

OBJECTIVE: Current type 2 diabetes (T2D) treatment guidelines include weight maintenance or loss, avoidance of hypoglycemia, and targets for blood pressure and circulating lipids, in addition to glycemic control. Increasingly, clinical trials and meta-analyses employ composite endpoints to capture the net clinical benefit of a given T2D intervention. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) represent a new class of injected antihyperglycemic agents that may be well suited to reaching many of these targets among patients failing on metformin monotherapy. RESEARCH DESIGNS AND METHODS: Using MEDLINE, Embase and Google Scholar, studies were sought that employed composite endpoints and that reported outcomes with exenatide and/or liraglutide. Bibliographies of relevant review articles were consulted to search for additional reports. RESULTS: Many trials have used the combination of HbA1c <7%, no weight gain and no hypoglycemic episodes as the composite endpoint in evaluating T2D therapies; however, at least 15 other distinct composite endpoints have been reported. Findings were relatively consistent across studies, regardless of how the composite endpoint was defined. Specifically, the GLP-1 RAs appear to be superior to other agents in their efficacy in providing T2D patients failing on metformin with a net clinical benefit, which can include avoidance of hyperglycemia and maintenance or improvement in body weight. CONCLUSIONS: Use of composite endpoints represents an important advance in T2D. While no single such endpoint has achieved dominance in the field, widely used composite endpoints capture efficacy in glycemic control as well as safety and effects on markers of cardiovascular risk.

Real-time continuous glucose monitoring versus internet-based blood glucose monitoring in adults with type 2 diabetes: a study of treatment satisfaction.

AIMS: To compare treatment satisfaction between real-time continuous glucose monitoring (RT-CGM) and internet-blood glucose monitoring (IBGM) in adults with type 2 diabetes treated with insulin. METHODS: This study recruited 40 patients who completed a parallel randomized controlled trial comparing a RT-CGM to an IBGM. Patients in the RT-CGM group monitored their blood-glucose levels bi-weekly and emailed results to their endocrinologist. Patients in the IBGM group also monitored their blood-glucose levels bi-weekly, but entered their data into an IBGM. Both groups used a secure website to submit blood-glucose readings and to receive feedback from their endocrinologist. Feedback included changes in therapy, suggestions on testing frequency, lifestyle modifications and/or encouragement to continue with no changes. At the end of 6 months, treatment satisfaction was measured using the 8-item Diabetes Treatment Satisfaction Questionnaire. In this study, "treatment" refers to the blood glucose monitoring system to which patients were randomized. RESULTS: Thirty-two of the 40 patients completed the treatment satisfaction questionnaire (80%). Compared to the RT-CGM group, the IBGM group reported a significantly higher level of overall treatment satisfaction (24.80 vs. 33.41, p<0.000). Ratings of individual satisfaction components including convenience, flexibility, likelihood of recommending treatment to others, and willingness to continue with treatment were also found to be significantly higher in the IBGM group. CONCLUSION: Patients using IBGM are more satisfied with their blood glucose monitoring system compared to those using RT-CGM.

Self-perceived health status following aneurysmal subarachnoid haemorrhage: a cohort study.

OBJECTIVE: The objective of the study was to assess the long-term self-reported health status and quality of life (QoL) of patients following an aneurysmal subarachnoid haemorrhage (ASAH) using a self-completed questionnaire booklet. DESIGN: A two-cohort study. SETTING: A regional tertiary neurosurgical centre. PARTICIPANTS: 2 cohorts of patients with ASAH treated between 1998 and 2008 and followed up at approximately 1 year. INTERVENTIONS: Routine care. PRIMARY AND SECONDARY OUTCOMES: A range of standardised scales included: AKC Short Sentences Test, the Barthel Index, the Self-Report Dysexecutive Questionnaire, the Everyday Memory Questionnaire, Stroke Symptom Checklist, Wimbledon Self-Report Scale, Modified Rankin Score (MRS) and a new Stroke-QoL. The data from summated scales were fit to the Rasch measurement model to validate the summed score. RESULTS: 214 patients (48%) returned the questionnaires; the majority (76%) had a World Federation of Neurosurgeons grade of 1 or 2. The most frequent aneurysm type was that of the anterior communicating artery (28%) with approximately 90% of aneurysms of the anterior circulation. Of those previously in full or part-time employment, 48.9% were unemployed at follow-up. All summated scales satisfied the Rasch measurement model requirements, such that their summed scores were a sufficient statistic. Given this, one-third of patients were noted to have a significant mood disorder and 25% had significant dysexecutive function. Patients with an MRS of 3, 4 or 5 had significantly worse scores on most outcome measures, but a significant minority of those with a score of zero had failed to return to work and displayed significant mood disorder. CONCLUSIONS: A range of self-reported cognitive and physical deficits have been highlighted in a cohort of patients with ASAH. While the MRS has been shown to provide a reasonable indication of outcome, in routine clinical follow-up it requires supplementation by instruments assessing dysexecutive function, memory and mood.

Breaking down patient and physician barriers to optimize glycemic control in type 2 diabetes.

Approximately half of patients with type 2 diabetes (T2D) do not achieve globally recognized blood glucose targets, despite the availability of a wide range of effective glucose-lowering therapies. Failure to maintain good glycemic control increases the risk of diabetes-related complications and long-term health care costs. Patients must be brought under glycemic control to improve treatment outcomes, but existing barriers to optimizing glycemic control must first be overcome, including patient nonadherence to treatment, the failure of physicians to intensify therapy in a timely manner, and inadequacies in the health care system itself. The reasons for such barriers include treatment side effects, complex treatment regimens, needle anxiety, poor patient education, and the absence of an adequate patient care plan; however, newer therapies and devices, combined with comprehensive care plans involving adequate patient education, can help to minimize barriers and improve treatment outcomes.

Early use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in type 2 diabetes.

OBJECTIVE: To evaluate the efficacy and safety of the available glucagon-like peptide-1 receptor agonists (GLP-1 RAs) exenatide and liraglutide (marketed as Byetta * and Victoza † , respectively) in first- or second-line pharmacotherapy for type 2 diabetes (T2D), described here as 'early use'. RESEARCH DESIGN AND METHODS: MEDLINE, EMBASE and Google Scholar databases were queried for clinical trial reports using the terms incretin, GLP-1, exenatide and liraglutide. Relevant articles were those that employed these agents in treatment-naïve patients with T2D and in patients who had failed on metformin monotherapy. Additional targeted searches were conducted on diabetes treatment guidelines and on the range of physiological responses to GLP-1 RAs. Most evidence is level I and II. RESULTS: Effective therapy for T2D should be implemented early in the course of this progressive disease. The recently revised 2013 Canadian Diabetes Association (CDA) guidelines now identify the GLP-1 RAs among various injected and oral agents recommended for the management of T2D. The rationale for early use of GLP-1 RAs in T2D management is manifold: these agents offer effective management of hyperglycemia in early-stage T2D, minimal risk of hypoglycemia, weight loss, improvement in multiple non-glycemic cardiovascular risk factors, and potential enhancement of patient adherence to antihyperglycemic treatment. Available data from clinical trials support second-line use of GLP-1 RAs among patients who fail on metformin, as well as first-line use of these agents in a subset of T2D patients. CONCLUSIONS: The ability to achieve glycemic targets using GLP-1 RAs while simultaneously avoiding hypoglycemia and weight gain could provide substantial reassurance to physicians and patients who might otherwise resist the transition to injected therapies. Exenatide and liraglutide represent appropriate second-line choices for pharmacological treatment of T2D, as indicated in the 2013 CDA guidelines.

Initiation of once daily insulin detemir is not associated with weight gain in patients with type 2 diabetes mellitus: results from an observational study.

BACKGROUND: Obesity is common in type 2 diabetes (T2DM) and is associated with increased risk of morbidity and all-cause mortality. This analysis describes weight changes associated with insulin detemir initiation in real-life clinical practice. METHODS: Study of Once-Daily Levemir (SOLVE) was a 24-week international observational study of once-daily insulin detemir as add-on therapy in patients with T2DM receiving oral hypoglycaemic agents (OHAs). RESULTS: 17,374 participants were included in the analysis: mean age 62 ± 12 years; weight 80.8 ± 17.6 kg; body mass index (BMI) 29.2 ± 5.3 kg/m2; diabetes duration 10 ± 7 years; HbA1c 8.9 ± 1.6%. HbA1c decreased by 1.3 ± 1.5% during the study, with insulin doses of 0.27 ± 0.17 IU/kg. Patients with higher BMI had higher pre-insulin HbA1c, and similar reductions in HbA1c with insulin therapy. Weight decreased from 80.8 ± 17.6 kg to 80.3 ± 17.0 kg (change of -0.6 [95% CI -0.65; -0.47] kg), with 35% of patients losing >1 kg. Patients with the highest pre-insulin BMI lost the greatest amount of weight: BMI < 25: +0.8 [95% CI: 0.6; 0.9] kg, 25 ≤ BMI < 30: -0.2 [95% CI: -0.3; -0.8] kg, 30 ≤ BMI < 35: -1.0 [95% CI: -1.1; -0.8] kg; BMI ≥ 35: -1.9 [95% CI: -2.2; -1.6] kg. Minor hypoglycaemia decreased with increasing BMI: 2.3 and 1.3 events per patient year for BMI <25 and ≥ 35, respectively. CONCLUSIONS: Overall, patients with poorly controlled T2DM achieved significant reductions in HbA1c after initiation of once-daily insulin detemir therapy, without weight gain. The favourable impact of insulin detemir on weight may not apply to other insulin preparations. TRIAL REGISTRATIONS: ClinicalTrials.gov, NCT00825643 and NCT00740519.

A comparison of internet monitoring with continuous glucose monitoring in insulin-requiring type 2 diabetes mellitus.

OBJECTIVE: To compare the effects of real-time continuous glucose monitoring (RT-CGM) and an Internet blood glucose monitoring system (IBGMS) on glycated hemoglobin levels in patients with type 2 diabetes mellitus treated with insulin. METHODS: Fifty-seven patients with type 2 diabetes treated with insulin were assigned randomly to 1 of 2 groups. Group 1 had the results of their self-monitoring of blood glucose level monitored biweekly using an IBGMS. Group 2 used RT-CGM and were monitored biweekly. Both groups used a secure website to upload data and to receive feedback from their endocrinologist. A1C and laboratory test results were collected at 0, 3 and 6 months. RESULTS: The baseline parameters were not significantly different. After a 6-month follow-up period, both IBGMS and RT-CGM showed significant within-group improvements in A1C level. In the IBGMS group, the A1C level decreased from 8.79%±1.25% to 7.96%±1.30% (p<0.05). The RT-CGM group decreased from 8.80%±1.37% to 7.49%±0.70% (p<0.001). IBGMS and RT-CGM did not show significantly different A1C levels at baseline, 3 and 6 months (p>0.05). CONCLUSIONS: The use of both IBGMS and RT-CGM significantly improved A1C levels in patients with type 2 diabetes treated with insulin in a randomized trial over a 6-month period. There were no significant differences in A1C values between groups after 6 months.

Efficacy and safety of linagliptin 2.5 mg twice daily versus 5 mg once daily in patients with type 2 diabetes inadequately controlled on metformin: a randomised, double-blind, placebo-controlled trial.

OBJECTIVE: Glycaemic control in patients with type 2 diabetes (T2DM) is often not achieved or not sustained using monotherapy such as metformin, necessitating the addition of other antihyperglycaemic agents. Linagliptin, a dipeptidyl peptidase-4 inhibitor, is licensed for 5 mg once-daily dosing. As metformin is administered twice daily, a fixed-dose combination of these compounds would require twice-daily administration of linagliptin. This study evaluated whether 2.5 mg twice-daily dosing of linagliptin has comparable efficacy and safety to 5 mg once-daily dosing when given in addition to metformin twice daily in patients with inadequate glycaemic control. METHODS: A total of 491 T2DM patients with glycated haemoglobin (HbA1c) 7.0-10.0% were randomised (5:5:1) to double-blind treatment with linagliptin 2.5 mg twice daily, 5 mg once daily or placebo, respectively, in addition to continuing metformin twice daily (≥1500 mg/day or maximally tolerated dose). The primary endpoint was change from baseline in HbA1c after 12 weeks. ClinicalTrials.gov, NCT01012037. RESULTS: Mean baseline HbA1c for all patients was 7.97%. After 12 weeks, linagliptin 2.5 mg twice daily and 5 mg once daily both significantly reduced HbA1c (placebo-adjusted changes from baseline -0.74% (95% CI -0.97, -0.52) and -0.80% (95% CI -1.02, -0.58), respectively, both p<0.0001). The treatment difference (twice daily-once daily) between the linagliptin regimens was 0.06 (95% CI -0.07, 0.19), the upper bound of which was less than the predefined noninferiority margin (0.35%). The overall incidence of adverse events with linagliptin 2.5 mg twice daily, 5 mg once daily and placebo was 43.0%, 34.8%, and 38.6% respectively. Hypoglycaemia was rare (3.1% with linagliptin 2.5 mg twice daily, 0.9% with 5 mg once daily, 2.3% with placebo) with no severe episodes. Study limitations include duration, patient population (mainly white) and absence of postprandial glucose data. CONCLUSIONS: Linagliptin 2.5 mg twice daily had non-inferior HbA1c-lowering effects after 12 weeks compared to 5 mg once daily, with comparable safety and tolerability, in T2DM patients inadequately controlled with metformin.

Lumbar drainage of cerebrospinal fluid after aneurysmal subarachnoid hemorrhage: a prospective, randomized, controlled trial (LUMAS).

BACKGROUND AND PURPOSE: A single-center prospective randomized controlled trial has been conducted to determine if lumbar drainage of cerebrospinal fluid after aneurysmal subarachnoid hemorrhage reduces the prevalence of delayed ischemic neurological deficit and improves clinical outcome. METHODS: Patients with World Federation of Neurological Surgeons Grade 1 to 3 aneurysmal subarachnoid hemorrhage and modified Fisher Grades 2, 3, 4, and 3+4 were randomized to either the study group of standard therapy plus insertion of a lumbar drain or the control group of standard therapy alone. The primary outcome measure was the prevalence of delayed ischemic neurological deficit. RESULTS: Two hundred ten patients with aneurysmal subarachnoid hemorrhage (166 female, 44 male; median age, 54 years; interquartile range, 45-62 years) were recruited into the control (n=105) and study (n=105) groups of the trial. World Federation of Neurological Surgeons grade was: 1 (n=139), 2 (n=60), and 3 (n=11); Fisher grade was: 2 (n=87), 3 (n=85), and 4 (n=38). The prevalence of delayed ischemic neurological deficit was 35.2% and 21.0% in the control and study groups, respectively (P=0.021). The prevalence of a modified Rankin Scale score of 4, 5, or 6 at Day 10 and 6 months, respectively, was 62.5% and 18.6% in the control group and 44.8% and 19.8% in the study group (P=0.009 and 0.83, respectively). CONCLUSIONS: Lumbar drainage of cerebrospinal fluid after aneurysmal subarachnoid hemorrhage has been shown to reduce the prevalence of delayed ischemic neurological deficit and improve early clinical outcome but failed to improve outcome at 6 months after aneurysmal subarachnoid hemorrhage. CLINICAL TRIAL REGISTRATION: URL: www.clinicaltrials.gov. Unique identifier: NCT00842049.

Barriers to effective insulin treatment: the persistence of poor glycemic control in type 2 diabetes.

BACKGROUND: Contrary to longstanding recommendations on type 2 diabetes (T2D) management, the de facto standard of care in Canada includes lag times of many years prior to introducing effective glycemic control. Even patients transitioned to insulin may continue to experience poor glycemic control, with attendant diabetic complications, suggesting poor adherence or inadequate dose titration. OBJECTIVE: To identify barriers to timely and effective use of insulin in T2D. METHODS: PubMed searches were conducted to find research articles on insulin initiation, adherence and intensification. Also, because recent data on the consequences of intensive glycemic control may be taken as justification for relaxing glycemic targets, a secondary search on this literature was conducted, including the UKPDS and ACCORD trials, plus post hoc and meta-analyses of these data. No formal evaluation of level of evidence was conducted while researching this narrative literature review. FINDINGS: Timely, effective glycemic control remains an important clinical goal but is complicated by patient, physician and treatment factors. Patient barriers to accepting insulin initiation include fear of hypoglycemia, injections and weight gain, and reluctance to accommodate the inflexible timing of scheduled insulin doses. Adherence issues, including dose omission, are common and are associated with some of the same factors. Fear of hypoglycemia also underlies many physicians' reluctance to prescribe insulin. Caregivers' failure to provide training or answer questions about insulin's risks and benefits was also associated with low patient adherence. Poor communication may also be at fault when patients on insulin fail to titrate or intensify their treatment adequately. Conversely, glycemic control can be significantly improved by facilitating ongoing communication between patients and caregivers. DISCUSSION: Although innovations in injectable therapy for T2D may help address the current pattern of poor glycemic control, improved communication between patients and caregivers is also a powerful approach and can be implemented with existing therapies.