Aims/IntroductionType 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 MethodsThis 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. ResultsAfter 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. ConclusionsIn 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.

The 2nd Diabetes Attitudes, Wishes and Needs (DAWN2) study examined policies/strategies, and perceptions of people with diabetes (PWD), healthcare professionals (HCPs) and family members (FMs) regarding patient-centred care and diabetes education in Canada and 16 other countries.

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 24weeks.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

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 DAWN2 study, conducted in 17 countries, including Canada, examined policies/strategies as well as perspectives of persons with diabetes (PWD) and healthcare professionals (HCPs) regarding psychosocial assessment and management.

Objectives: DAWN2 assessed the psychosocial impact of diabetes on persons with diabetes (PWDs), family members and healthcare professionals (HCPs) across 17 countries. This article reports on the Canadian cohort of PWDs.Methods: PWDs completed online, validated self-report scales assessing quality of life (QOL), self-management, beliefs, social support and priorities for improving diabetes care. Analyses used unweighted data.Results: Of 500 participants (80 type 1, 420 type 2) positive self-reported QOL was common (64.6%) and likely depression less common (12.8%). Diabetes distress, however, was identified by almost half of PWDs with type 1 diabetes, and one-quarter of PWDs with type 2 (47.5% vs. 25.7% type 2; p<0.001). Numerous life areas were negatively impacted, particularly finances, work and emotional well-being for those with type 1 diabetes (p<0.001 vs. type 2). Most PWDs reported support from family, friends and HCPs, but few reported being asked by HCPs how diabetes affected their lives. Most PWDs participated in (type 1, 90.0%; type 2, 85.7%) and valued (type 1, 84.7%; type 2, 78.1%) diabetes education. Few PWDs relied on community supports (type 1, 17.5%; type 2, 26.9%), and discrimination was not uncommon for those with type 1 (33.8% vs. 12.4% for type 2; p<0.001).Conclusions: PWDs experience psychological challenges that should be addressed within diabetes management services. (C) 2015 Canadian Diabetes Association.

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.

Glycemic control is the core of diabetes care and is associated with reduced risk for complications in type 1 and type 2 diabetes ( 1 The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med. 1993; 329: 977-986 Crossref PubMed Scopus (22702) Google Scholar , 2 Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998; 352: 837-853 Abstract Full Text Full Text PDF PubMed Scopus (18951) Google Scholar , 3 Holman R.R. Paul S.K. Bethel M.A. et al. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008; 359: 1577-1589 Crossref PubMed Scopus (5242) Google Scholar , 4 Nathan D.M. Cleary P.A. Backlund J.Y. et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med. 2005; 353: 2643-2653 Crossref PubMed Scopus (4135) Google Scholar , 5 Nathan D.M. Group D.E.R. The diabetes control and complications trial/epidemiology of diabetes interventions and complications study at 30 years: Overview. Diabetes Care. 2014; 37: 9-16 Crossref PubMed Scopus (819) Google Scholar ). Randomized controlled clinical trials have shown that glycemic control reduces the chance for macrovascular and microvascular complications ( 3 Holman R.R. Paul S.K. Bethel M.A. et al. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008; 359: 1577-1589 Crossref PubMed Scopus (5242) Google Scholar , 4 Nathan D.M. Cleary P.A. Backlund J.Y. et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med. 2005; 353: 2643-2653 Crossref PubMed Scopus (4135) Google Scholar , 5 Nathan D.M. Group D.E.R. The diabetes control and complications trial/epidemiology of diabetes interventions and complications study at 30 years: Overview. Diabetes Care. 2014; 37: 9-16 Crossref PubMed Scopus (819) Google Scholar ), so current treatment guidelines emphasize timely interventions for patients so they can reach appropriate glycemic targets within months of their diagnoses ( 6 Cheng A.Y. Lau D.C. The Canadian Diabetes Association 2013 clinical practice guidelines: Raising the bar and setting higher standards!. Can J Diabetes. 2013; 37: 137-138 Abstract Full Text Full Text PDF Scopus (27) Google Scholar ). However, more than half of North American patients remain above the glycemic target of glycated hemoglobin (A1C) <7% ( 7 Braga M. Casanova A. Teoh H. et al. Treatment gaps in the management of cardiovascular risk factors in patients with type 2 diabetes in Canada. Can J Cardiol. 2010; 26: 297-302 Abstract Full Text PDF PubMed Scopus (69) Google Scholar , 8 Hoerger T.J. Segel J.E. Gregg E.W. et al. Is glycemic control improving in U.S. adults?. Diabetes Care. 2008; 31: 81-86 Crossref PubMed Scopus (413) Google Scholar , 9 Ali M.K. Bullard K.M. Saaddine J.B. et al. Achievement of goals in U.S. diabetes care, 1999-2010. N Engl J Med. 2013; 368: 1613-1624 Crossref PubMed Scopus (731) Google Scholar ).

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. (C) 2015 Canadian Diabetes Association

AimsTo evaluate glucose‐lowering treatment strategies with linagliptin and metformin in people with newly diagnosed type 2 diabetes and marked hyperglycaemia, a prevalent population for which few dedicated studies of oral antidiabetes drugs have been conducted.MethodsA total of 316 patients, with type 2 diabetes diagnosed for ≤12 months and with glycated haemoglobin (HbA1c) concentration in the range 8.5–12.0%, were randomized 1:1 to double‐blind, free‐combination treatment with linagliptin 5 mg once daily and metformin twice daily (uptitrated to 2000 mg/day maximum) or to linagliptin monotherapy. The primary endpoint was change in HbA1c concentration from baseline at week 24 (per‐protocol completers' cohort: n = 245).ResultsThe mean (standard deviation) age and HbA1c at baseline were 48.8 (11.0) years and 9.8 (1.1)%, respectively. At week 24, the mean ± standard error (s.e.) HbA1c decreased from baseline by –2.8 ± 0.1% with linagliptin/metformin and –2.0 ± 0.1% with linagliptin; a treatment difference of –0.8% (95% confidence interval –1.1 to –0.5; p <0.0001). Similar results were observed in a sensitivity analysis based on intent‐to‐treat principles: adjusted mean ± s.e. changes in HbA1c of –2.7 ± 0.1% and –1.8 ± 0.1%, respectively; treatment difference of –0.9% (95% CI –1.3 to –0.6; p <0.0001). A treatment response of HbA1c <7.0% was achieved by 61 and 40% of patients in the linagliptin/metformin and linagliptin groups, respectively. Few patients experienced drug‐related adverse events (8.8 and 5.7% of patients in the linagliptin/metformin and linagliptin groups, respectively). Hypoglycaemia occurred in 1.9 and 3.2% of patients in the linagliptin/metformin and linagliptin groups, respectively (no severe episodes). Body weight decreased significantly with the combination therapy (–1.3 kg between‐group difference; p =0.0033).ConclusionsLinagliptin in initial combination with metformin in patients with newly diagnosed type 2 diabetes and marked hyperglycaemia, an understudied group, elicited significant improvements in glycaemic control with a low incidence of hypoglycaemia, weight gain or other adverse effects. These results support early combination treatment strategies and suggest that newly diagnosed patients with marked hyperglycaemia may be effectively managed with oral, non‐insulin therapy.

Patients with type 2 diabetes mellitus ( T2DM ) with a glycated haemoglobin ( HbA1c ) level ≥7 and ≤10% were randomized to receive empagliflozin 12.5 mg twice daily (n = 219), 25 mg once daily (n = 218), 5 mg twice daily (n = 219) or 10 mg once daily (n = 220), or placebo (n = 107) as add‐on to stable‐dose metformin immediate release ( IR ) twice daily for 16 weeks. The primary endpoint was change from baseline in HbA1c at week 16. At week 16, change from baseline in HbA1c with empagliflozin twice daily was non‐inferior to empagliflozin once daily and vice versa. The adjusted mean (95% confidence interval) difference in change from baseline in HbA1c with empagliflozin 12.5 mg twice daily versus 25 mg once daily was −0.11% (−0.26, 0.03), and with empagliflozin 5 mg twice daily versus 10 mg once daily it was −0.02% (−0.16, 0.13). All empagliflozin regimens were well tolerated; thus, when used as add‐on to metformin IR in patients with T2DM , the therapeutic effect of empagliflozin twice‐daily and once‐daily regimens can be considered equivalent.

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.

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. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

The DAWN2 study involved 17 countries, including Canada, and enrolled people with diabetes (PWD), family members (FMs) and healthcare professionals (HCPs) to identify required areas of improvement in diabetes self-management and psychosocial factors. In Canada, 500 PWD, 121 FMs and 280 HCPs were recruited, and completed surveys of validated, adapted and newly developed questions. Data were descriptively analyzed. Results, presented as percent of responses, indicated that substantial improvements were required by PWD regarding eating healthily (78% PWD, 62% FMs, 64% HCPs), being physically active (74% PWD, 74% FMs, 80% HCPs) and maintaining healthy weight (70% PWD, 57% FMs, 72% HCPs). Of HCPs, 57% reported that diabetes self-management education and psychological support and care resources needed to be more available for PWD. Further, HCPs said it would be helpful if PWD prepared questions about their diabetes in advance of consultation (86%), told HCPs how to best support them (86%), independently sought information they needed to self-manage (77%) and participated in community activities for improved diabetes care and support (90%). HCPs also felt that diabetes medications needed to be more affordable (62%) and that PWD required better access to the newest diabetes treatments (50%), basic medications (23%) and blood sugar testing supplies/devices (27%). FMs (62%) wanted to know how to deal positively with emotional issues of living with diabetes. Acceptance of people with diabetes as equal members of society still needed addressing (28% PWD, 11% FMs, 11% HCPs). Improvements in all areas depend on the collaboration of HCPs, FMs and PWD.

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 1year.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.