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Atlanta, GA, United States

Heller S.,University of Sheffield | Buse J.,University of North Carolina at Chapel Hill | Fisher M.,Royal Infirmary | Garg S.,Barbara Davis Center for Childhood Diabetes | And 9 more authors.
The Lancet | Year: 2012

Background Intensive basal-bolus insulin therapy has been shown to improve glycaemic control and reduce the risk of long-term complications that are associated with type 1 diabetes mellitus. Insulin degludec is a new, ultra-longacting basal insulin. We therefore compared the efficacy and safety of insulin degludec and insulin glargine, both administered once daily with mealtime insulin aspart, in basal-bolus therapy for type 1 diabetes. Methods In an open-label, treat-to-target, non-inferiority trial, undertaken at 79 sites (hospitals and centres) in six countries, adults (aged =18 years) with type 1 diabetes (glycated haemoglobin [HbA 1c] =10% [86 mmol/mol]), who had been treated with basal-bolus insulin for at least 1 year, were randomly assigned in a 3:1 ratio, with a computergenerated blocked allocation sequence, to insulin degludec or insulin glargine without stratification by use of a central interactive response system. The primary outcome was non-inferiority of degludec to glargine, assessed as a reduction in HbA 1c after 52 weeks, with the intention-to-treat analysis. This trial is registered with ClinicalTrials.gov, number NCT00982228. Findings Of 629 participants, 472 were randomly assigned to insulin degludec and 157 to insulin glargine; all were analysed in their respective treatment groups. At 1 year, HbA 1c had fallen by 0•40% points (SE 0•03) and 0•39% points (0•07), respectively, with insulin degludec and insulin glargine (estimated treatment diff erence -0•01% points [95% CI -0•14 to 0•11]; p<0•0001 for non-inferiority testing) and 188 (40%) and 67 (43%) participants achieved a target HbA 1c of less than 7% (<53 mmol/mol). Rates of overall confirmed hypoglycaemia (plasma glucose <3•1 mmol/L or severe) were similar in the insulin degludec and insulin glargine groups (42•54 vs 40•18 episodes per patient-year of exposure; estimated rate ratio [degludec to glargine] 1•07 [0•89 to 1•28]; p=0•48). The rate of nocturnal confirmed hypoglycaemia was 25% lower with degludec than with glargine (4•41 vs 5•86 episodes per patient-year of exposure; 0•75 [0•59 to 0•96]; p=0•021). Overall serious adverse event rates (14 vs 16 events per 100 patient-years of exposure) were similar for the insulin degludec and insulin glargine groups. Interpretation Insulin degludec might be a useful basal insulin for patients with type 1 diabetes because it provides eff ective glycaemic control while lowering the risk of nocturnal hypoglycaemia, which is a major limitation of insulin therapy. Source

Canagliflozin is a sodium glucose co-transporter 2 inhibitor developed for the treatment of patients with type 2 diabetes mellitus (T2DM). Our randomized, double-blind, placebo-controlled, phase 3 study (www.clinicaltrials.gov: NCT01106651) evaluated the efficacy and safety of canagliflozin therapy in older subjects (aged 55-80 years) with T2DM inadequately controlled on their current regimen of blood glucose-lowering agents (any approved oral or injectable treatment). Subjects (N = 716) aged 55 to 80 years (mean, 63.6 years) with glycated hemoglobin (HbA1c) levels ≥ 7.0% to ≤ 10.0% were randomized. Seven hundred fourteen received canagliflozin 100 mg or 300 mg or placebo (1:1:1) daily. The prespecified primary endpoint was change from baseline in HbA1c level at week 26. Prespecified secondary endpoints included proportion of subjects achieving HbA1c levels < 7.0%, change from baseline in fasting plasma glucose (FPG) level and systolic blood pressure (BP), and percent change from baseline in body weight, triglyceride levels, and high-density lipoprotein cholesterol (HDL-C) level. Adverse events (AEs) were reported throughout the study. At week 26, treatment with canagliflozin 100 mg and 300 mg significantly reduced HbA1c levels compared with placebo (-0.60%, -0.73%, -0.03%, respectively; P < 0.001); more subjects achieved HbA1c levels < 7.0% with both canagliflozin doses compared with placebo (P < 0.001). Both canagliflozin doses significantly reduced body weight, FPG level, and systolic BP, and increased HDL-C level compared with placebo (P < 0.001); low-density lipoprotein cholesterol level was increased with both canagliflozin doses compared with placebo. The overall AE incidence was slightly higher with canagliflozin 300 mg than with canagliflozin 100 mg or placebo (78.0%, 72.2%, 73.4%, respectively). Serious AE and AE-related discontinuation rates were low across groups. Both canagliflozin doses were associated with higher rates than placebo of genital mycotic infections, urinary tract infections, and osmotic diuresis-related AEs (ie, pollakiuria, polyuria). Documented hypoglycemia rates were modestly higher with both canagliflozin doses compared with placebo. Canagliflozin improved glycemic control, reduced body weight and systolic BP, and was generally well tolerated in older subjects with T2DM who were on background therapy with a variety of blood glucose-lowering agents. Source

Bode B.,Atlanta Diabetes Associates
The American journal of managed care | Year: 2011

Liraglutide is an analog with 97% homology to human glucagon-like peptide (GLP-1) and acts as a GLP-1 receptor agonist. Several large, randomized, multicenter phase 3 trials evaluated the efficacy and safety of liraglutide by comparing monotherapy and combination therapy with other antidiabetic medications in adult patients with type 2 diabetes. The Liraglutide Effect and Action in Diabetes (LEAD) program demonstrated that liraglutide, when used alone or in combination with other antidiabetic medications, effectively controls hyperglycemia (glycosylated hemoglobin [A1C] reductions up to 1.6%) and assists patients in meeting established glycemic targets. Compared with certain other classes of antidiabetic agents, liraglutide is associated with a lower risk of hypoglycemia. Liraglutide has also been associated with weight loss (1.8 to 3.4 kg) and improved patient satisfaction and health-related quality of life. Several studies have demonstrated that GLP-1 receptor agonists may improve pancreatic beta cell function, which may delay disease progression if maintained over the long term. As with any drug, liraglutide is not without risk, and a patient's complete clinical status and benefit-to-risk profile should be considered before prescribing treatment. For patients with type 2 diabetes who have failed to achieve glycemic control through diet and exercise, liraglutide may be an important treatment option. The current consensus statement of the American Association of Clinical Endocrinologists (AACE) and the American College of Endocrinology (ACE) cites efficacy and low risk of hypoglycemia in preferring GLP-1 agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors over sulfonylureas and glinides, after initial treatment with metformin. The guidelines prefer GLP-1 agonists over DPP-4 inhibitors because of their actions that promote weight loss and their somewhat greater effectiveness in reducing postprandial glucose excursions. Source

Asche C.V.,Illinois College | Bode B.,Atlanta Diabetes Associates | Busk A.K.,Novo Nordisk AS | Nair S.R.,Cardiff Research Consortium
Diabetes, Obesity and Metabolism | Year: 2012

Aim: To study the clinical and economic benefits associated with adequate and early initiation and intensification of insulin in people with type 2 diabetes mellitus (T2DM). Methods: A systematic review was performed using published articles from January 2000 to August 2010 that linked intervention, disease, study design and outcomes. Studies were further classified as initiation and intensification based on predefined criteria. Individual studies in systematic reviews and meta-analysis were searched and included if relevant. Results: A total of 2690 articles were screened with 76 (40 initiation and 36 intensification) studies included. Most initiation studies had mean baseline HbA1c values of >8.5%. The endpoint HbA1c values were reduced with insulin treatment in these studies, with endpoint values ranging from 6.6 to 9.8%. Similar results were seen with the intensification studies (endpoint HbA1c: 6.4-9.6%). Addition of insulin to oral antidiabetics (OADs) resulted in better glycaemic control in most studies. Blood glucose levels reduced substantially with OADs + insulin compared with OADs alone. Quality of life outcomes and treatment satisfaction were reported in six studies and not significantly different for insulin vs. OADs. Hypoglycaemic events were manageable with insulin initiation. However, all insulin types were associated with weight gain although the comparison with OADs elicited varying results. Conclusions: Proactive management with early insulin initiation and intensification should be considered in people with T2DM in inadequate glycaemic control. The economic benefits with early initiation and intensification have to be fully explored. © 2011 Blackwell Publishing Ltd. Source

Bode B.W.,Atlanta Diabetes Associates
Diabetes Technology and Therapeutics | Year: 2010

Continuous subcutaneous insulin infusion (CSII) for type 2 diabetes mellitus (T2DM) is a promising therapy, but the clinical evidence supporting it is mixed. Large randomized controlled trials have concluded that CSII was equivalent to multiple daily injections (MDI), whereas smaller trials have concluded that CSII was superior. Simpler insulin regimens of CSII have been investigated for T2DM and may lead to improved outcomes. Future directions in this area include simpler insulin pumps and the use of concentrated insulins (U-500), neither of which has left the feasibility stage of research. CSII may be appropriate for some people with T2DM, especially those for whom MDI therapy has failed. © 2010, Mary Ann Liebert, Inc. Source

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