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Nicollet, MN, United States

Wright E.E.,Cape Fear Valley Health System | Stonehouse A.H.,Amylin Pharmaceuticals Inc. | Cuddihy R.M.,International Diabetes Center
Diabetes, Obesity and Metabolism | Year: 2010

Type 2 diabetes (T2DM) is a multifaceted disease, characterized by hyperglycaemia, resulting from a combination of insulin resistance, impaired incretin action and β-cell dysfunction leading to relative insulin deficiency. Although traditional anti-diabetes agents improve hyperglycaemia, they do so at a cost, which may entail hypoglycemia and increased body weight; exacerbating dyslipidemia, hypertension and components of insulin resistance and metabolic syndrome associated with T2DM-potentially increasing cardiovascular risk. At diagnosis, many patients with T2DM are treated with medical nutritional therapy (MNT) and exercise, then single or multiple oral anti-diabetes agents until treatment failure, when insulin is used. This strategy has been challenged by recommendations for polypharmacy approaches to the treatment of T2DM, as current strategies are unable to improve multiple aspects of the disease, nor are they likely to address underlying pathophysiology. Although the 2009 American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) treatment algorithm recommends a stepwise approach with MNT and metformin, later adding oral agents, incretin-based therapies or insulin, some experts have recommended a more aggressive approach. In his 2008 ADA Banting Lecture, Dr. Ralph DeFronzo recommended early treatment with metformin, TZD and exenatide at initiation of therapy. The authors' of this article recommend an aggressive early polypharmacy approach addressing underlying pathophysiology, including the incretin defect-with MNT and exercise, metformin and an incretin-based therapy and/or basal insulin if glycemic goal is not achieved within 3 months. This approach attempts to modify the disease, aiming for tight glycemic control, weight loss, reduced hypoglycemia, improvements to hypertension, dyslipidemia and insulin resistance-and improved cardiovascular outcomes. © 2010 Amylin Pharmaceuticals, Inc. Source


Miller K.M.,Jaeb Center for Health Research | Beck R.W.,Jaeb Center for Health Research | Bergenstal R.M.,International Diabetes Center | Goland R.S.,Columbia University | And 5 more authors.
Diabetes Care | Year: 2013

Objective-Despite substantial evidence of the benefit of frequent self-monitoring of blood glucose (SMBG) in type 1 diabetes, certain insurers limit the number of test strips that they will provide. The large database of the T1D Exchange clinic registry provided an opportunity to evaluate the relationship between the number of SMBG measurements per day and HbA1c levels across a wide age range of children and adults. Research design and methods-The analysis included 20,555 participants in the T1D Exchange clinic registry with type 1 diabetes ≥1 year and not using a continuous glucose monitor (11,641 younger than age 18 years and 8,914 18 years old or older). General linear models were used to assess the association between the number of SMBG measurements and HbA1c levels after adjusting for potential confounding variables. ResultsA higher number of SMBG measurements per day were associated with non- Hispanic white race, insurance coverage, higher household income, and use of an insulin pump for insulin delivery (P,0.001 for each factor). After adjusting for these factors, a higher number of SMBG measurements per day was strongly associated with a lower HbA1c level (adjusted P, 0.001), with the association being present in all age-groups and in both insulin pump and injection users. Conclusions-There is a strong association between higher SMBG frequency and lower HbA1c levels. It is important for insurers to consider that reducing restrictions on the number of test strips provided per month may lead to improved glycemic control for some patients with type 1 diabetes. © 2013 by the American Diabetes Association. Source


White W.B.,University of Connecticut | Cannon C.P.,Harvard University | Heller S.R.,University of Sheffield | Nissen S.E.,Cleveland Clinic | And 9 more authors.
New England Journal of Medicine | Year: 2013

BACKGROUND: To assess potentially elevated cardiovascular risk related to new antihyperglycemic drugs in patients with type 2 diabetes, regulatory agencies require a comprehensive evaluation of the cardiovascular safety profile of new antidiabetic therapies. We assessed cardiovascular outcomes with alogliptin, a new inhibitor of dipeptidyl peptidase 4 (DPP-4), as compared with placebo in patients with type 2 diabetes who had had a recent acute coronary syndrome. METHODS: We randomly assigned patients with type 2 diabetes and either an acute myocardial infarction or unstable angina requiring hospitalization within the previous 15 to 90 days to receive alogliptin or placebo in addition to existing antihyperglycemic and cardiovascular drug therapy. The study design was a double-blind, noninferiority trial with a prespecified noninferiority margin of 1.3 for the hazard ratio for the primary end point of a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. RESULTS: A total of 5380 patients underwent randomization and were followed for up to 40 months (median, 18 months). A primary end-point event occurred in 305 patients assigned to alogliptin (11.3%) and in 316 patients assigned to placebo (11.8%) (hazard ratio, 0.96; upper boundary of the one-sided repeated confidence interval, 1.16; P<0.001 for noninferiority). Glycated hemoglobin levels were significantly lower with alogliptin than with placebo (mean difference, -0.36 percentage points; P<0.001). Incidences of hypoglycemia, cancer, pancreatitis, and initiation of dialysis were similar with alogliptin and placebo. CONCLUSIONS: Among patients with type 2 diabetes who had had a recent acute coronary syndrome, the rates of major adverse cardiovascular events were not increased with the DPP-4 inhibitor alogliptin as compared with placebo. Copyright © 2013 Massachusetts Medical Society. Source


Bergenstal R.M.,International Diabetes Center | Li Y.,Amylin Pharmaceuticals Inc. | Porter T.K.B.,Amylin Pharmaceuticals Inc. | Weaver C.,Amylin Pharmaceuticals Inc. | Han J.,Amylin Pharmaceuticals Inc.
Diabetes, Obesity and Metabolism | Year: 2013

Aims: Type 2 diabetes mellitus (T2DM) is often associated with cardiovascular (CV) risk factors such as obesity, hypertension and dyslipidemia. The objective of this analysis was to evaluate potential effects of exenatide once weekly (ExQW), a GLP-1 receptor agonist, on glycaemic control and CV risk factors. Methods: This analysis included 675 Intent-to-Treat patients with T2DM [baseline (mean ± SD) HbA1c, 8.1±1.2%; fasting blood glucose (FBG), 166±48mg/dl; weight, 94.3±19.4kg; systolic/diastolic blood pressure (SBP/DBP), 129±15/78 ± 9 mmHg; total cholesterol, 178.5±41.9mg/dl; low-density lipoprotein (LDL), 100.1±35.0mg/dl; high-density lipoprotein (HDL), 44.5±11.6mg/dl; triglycerides, 155.6±3.3mg/dl; alanine aminotransferase (ALT), 32.1±19.5 U/l] treated with diet and exercise alone or in combination with metformin, sulfonylurea, and/or thiazolidinedione who received 52weeks of ExQW in four clinical trials. Results: At 52weeks, ExQW significantly improved HbA1c [mean (SE) change from baseline, -1.3 (0.05)%], FBG [-36.3 (2.02) mg/dl], body weight [-2.6 (0.19) kg], SBP/DBP [-3.6 (0.56) mmHg/-1.2 (0.34) mmHg], total cholesterol, -4.4 (1.33) mg/dl; LDL, -2.6 (1.08) mg/dl; HDL, 1.1 (0.31) mg/dl; triglycerides, -7 (1.6)%], and ALT [-4.3 (0.71) IU/l] concentrations, with greater improvements in patients with elevated analyte levels at baseline. Improvements were observed across a range of background antihyperglycaemia therapies. Of patients completing 52weeks, 19% achieved the composite American Diabetes Association goal (HbA1c < 7.0%, BP < 130/80 mmHg, LDL<100 mg/dl), compared to 1% at baseline. Nearly half (48%) achieved HbA1c < 7.0% without weight gain or major/minor hypoglycaemia. Nausea was the most frequent adverse event and was predominantly mild. Hypoglycaemia was infrequent, and more common with a sulfonylurea. Conclusions: With 52weeks of ExQW, patients experienced sustained improvements in glycaemic control and CV risk factors, with an increased likelihood of achieving both a clinically relevant composite outcome (HbA1c<7% without weight gain or increased risk of hypoglycaemia) and a composite of key therapeutic goals (HbA1c<7%, BP < 130/80 mmHg, LDL<100 mg/dl). © 2012 Blackwell Publishing Ltd. Source


Davies M.,University of Leicester | Pratley R.,University of Vermont | Hammer M.,Novo Nordisk AS | Thomsen A.B.,Novo Nordisk AS | Cuddihy R.,International Diabetes Center
Diabetic Medicine | Year: 2011

Aims Patient-reported outcomes from clinical trials offer insight into the impact of disease on health-related quality of life, including treatment satisfaction. This patient-reported outcomes evaluation was a substudy of a 26-week randomized, open-label trial comparing the once-daily injectable human GLP-1 analogue liraglutide with once-daily oral sitagliptin, both added to metformin. The patient reported outcomes substudy aimed to evaluate treatment satisfaction using the Diabetes Treatment Satisfaction Questionnaire (DTSQ) at baseline and 26weeks. Methods In the main 26-week randomized, open-label study (n=658), liraglutide, 1.2 or 1.8mg, injected with a pen, led to greater HbA1c reduction than oral sitagliptin, 100mg once daily, both added to metformin=1500mg daily: mean HbA1c reduction was 1.5, 1.2 and 0.9% (7, 10 and 14mmol/mol) for liraglutide 1.8mg, 1.2mg and sitagliptin, respectively (P<0.0001 for both liraglutide doses vs. sitagliptin) and liraglutide patients lost more weight (3 vs.1kg; P<0.0001). In this patient-reported outcomes substudy (liraglutide 1.8mg, n=171; 1.2mg, n=164; sitagliptin, n=170) DTSQ scores were analyzed by ANCOVA with treatment and country as fixed effects and baseline value as covariate. Results Overall treatment satisfaction, calculated by adding satisfaction scores for 'current treatment', 'convenience', 'flexibility', 'understanding', 'recommend', and 'continue', improved in all groups at 26weeks; greater improvement with liraglutide (4.35 and 3.51 vs. 2.96; P=0.03 for liraglutide 1.8mg vs. sitagliptin) may reflect greater HbA1c reduction and weight loss. Patients perceived themselves to be hyperglycaemic significantly less frequently with liraglutide 1.8mg (difference=-0.88; P<0.0001) and 1.2mg (difference=-0.49; P=0.01). Perceived frequency of hypoglycaemia was similar across all groups. Conclusions Injectable liraglutide may lead to greater treatment satisfaction than oral sitagliptin, potentially by facilitating greater improvement in glycaemic control, weight loss and/ or perception of greater treatment efficacy. © 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK. Source

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