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NDEI Clinical Insights in Diabetes eNewsletter Nov 2012 - National ...

CLINICAL INSIGHTS ® in DiabetesMore on effects of bariatric surgery on diabetes incidence: Results from SOSSimilar to the study by Adams and colleagues, the Swedish Obese Subjects (SOS) studyalso looked at long-term outcomes of bariatric surgery. SOS compared the effects of banding,vertical banded gastroplasty, or gastric bypass with the effects of usual care (weight loss withprofessional guidance or no professional guidance) for type 2 diabetes prevention among3,429 subjects with obesity. Key fi ndings:• Rate of diabetes incidence was 6.8 cases/1,000 person-years in the bariatric surgerygroup vs 28.4 cases/1,000 person-years in the control group based on 15-yearincidence data• 78% reduction in the long-term incidence of type 2 diabetes with bariatric surgery vsusual care• All bariatric surgery was associated with reduced type 2 diabetes incidence• When data were examined at 2 and 10 years of follow-up, sensitivity analyses showedthat the effects of surgery on diabetes incidence were at least as strong as at 15 yearsof follow-upCheck the “Metabolic Surgery& Diabetes” category in Slide Library forslides on SOS.Carlsson LM, Peltonen M, Ahlin S, et al. Bariatric surgery and prevention of type 2 diabetes in Swedishobese subjects. N Engl J Med. 2012;367:695-704.Switching from Sitagliptin to Liraglutide for Treatment of Type 2 Diabetes:Exploring Potential BenefitsTwo classes of incretin therapies arecurrently available for treatment of type 2diabetes: dipeptidyl peptidase-4 (DPP-4)inhibitors and glucagon-like peptide-1 (GLP-1)receptor agonists. The mechanisms of actionfor both classes is through increasing insulinsecretion and decreasing glucagon secretion in aglucose-dependent manner; the GLP-1 receptoragonists also slow gastric emptying and increasesatiety. 1 How do these two incretins compareregarding treatment of type 2 diabetes?In 2011, Pratley and colleagues reported 52-weekdata from a trial that explored treatment with theDPP-4 inhibitor, sitagliptin,and the GLP-1 receptoragonist, liraglutide, among subjects with type 2diabetes and A1C 7.5%–10%. 2 Participants hadbeen receiving metformin ≥1,500 mg/day for≥3 months; they continued metformin treatmentand were randomized to sitagliptin 100 mg/day,or liraglutide 1.2 mg/day or 1.8 mg/day. Theprimary composite endpoint was A1C

CLINICAL INSIGHTS ® in DiabetesSwitching from Sitagliptin to Liraglutide for Treatment of Type 2 Diabetes:Exploring Potential Benefits Continued• FPG: liraglutide 1.2 mg: 14.4 mg/dLdecrease (P=0.004); liraglutide 1.8 mg:25.2 mg/dL decrease (P

CLINICAL INSIGHTS ® in DiabetesMortality Among Normal and Overweight/Obese Subjects With Diabetes:Data from a Pooled AnalysisDo mortality rates differ for normal vsoverweight/obese patients with diabetes?Carnethon and colleagues analyzed datafrom fi ve clinical trials to compare mortality ratesamong subjects who were normal weight withsubjects who were overweight/obese at the timeof incident adult-onset diabetes.The study included 2,625 subjects (men andwomen aged >40 years who developed incidentdiabetes) from the following trials: 1-5• Atherosclerosis Risk in Communities (ARIC)• Cardiovascular Health Study (CHS)• Coronary Artery Risk Development in YoungAdults (CARDIA)• Framingham Offspring Study (FOS)• Multi-Ethnic Study of Atherosclerosis (MESA)Diabetes was determined as either fastingglucose ≥126 mg/dL or reported new use oforal antihyperglycemic medications or insulin atfollow-up examinations. Incident diabetes wasdetermined among subjects who were free fromdiabetes at baseline and met one of the abovecriteria.Obesity categories were defi ned as follows:normal weight, body mass index (BMI) 18.5-24.9 kg/m 2 ; overweight, BMI 25-29.9 kg/m 2 ; andobese, BMI ≥30 kg/m 2 .Total, cardiovascular (CV; myocardial infarction,stroke), and non-CV mortality were the mainoutcome measures.Results:Among the trials analyzed, there were 449 totaldeaths during follow-up (18 causes of death werenot classifi ed).• Death from CV cause: 178 deaths (6.8%)• Death from non-CV cause: 253 deaths(10.4%) (See Figure.)Across cohorts, 293 subjects (11.2%) had normalweightdiabetes. Normal-weight subjects hadsignifi cantly higher total and non-CV mortality vsthose who were overweight/obese. (See Figure attop of next column.)• Normal-weight subjects (rate per10,000 person-years):○ Total mortality: 284.4○ CV mortality: 99.8○ Non-CV mortality: 198.1• Overweight/obese subjects (rate per10,000 person-years):○ Total mortality: 152.1○ CV mortality: 67.8○ Non-CV mortality: 87.9After adjustment for covariates (age, race, sex,education, waist circumference, total cholesterol,HDL-C, systolic blood pressure, and smoking),normal-weight subjects with diabetes had• Signifi cantly elevated total and non-CVmortality that was consistent across cohorts,although not always statistically signifi cant:total mortality, hazard ratio (HR), 2.08 (95%confi dence interval [CI], 1.52-2.85); CVmortality, HR, 1.52 (95% CI, 0.89-2.58); non-CV mortality, HR 2.32 (95% CI, 1.55-3.48).• Higher mortality from all causes across sex,age, race, smoking subgroups vs obese/overweight subjects.1. Friedman GD, Cutter GR, Donahue RP, et al.CARDIA: study design, recruitment, and somecharacteristics of the examined subjects. J ClinEpidemiol. 1988;41(11):1105-1116.2. Fried LP, Borhani NO, Enright P, et al. TheCardiovascular Health Study: design and rationale. AnnEpidemiol. 1991;1(3):263-276.3. ARIC Investigators. The Atherosclerosis Risk inCommunities (ARIC) Study: design and objectives. AmJ Epidemiol. 1989;129(4):687-702.4. Bild DE, Bluemke DA, Burke GL, et al. Multi-ethnicstudy of atherosclerosis: objectives and design. Am JEpidemiol. 2002;156(9):871-881.5. Feinleib M, Kannel WB, Garrison RJ, McNamara PM,Castelli WP. The Framingham Offspring Study: designand preliminary data. Prev Med. 1975;4(4):518-525.Carnethon MR, De Chavez PJ, Biggs ML, et al.Association of weight status with mortality in adults withincident diabetes. JAMA. 2012;308(6):581-590.KnowledgePoint360 Group, LLC125 Chubb AvenueLyndhurst, NJ 07071pg 6

CLINICAL INSIGHTS ® in DiabetesRelationship Between DPP-4 Inhibitors and Cardiovascular Event Risk:Meta-analysisDipeptidyl peptidase-4 (DPP-4) inhibitorsare one of fi ve drug classes recommendedin the 2012 position statement from theAmerican Diabetes Association (ADA) and theEuropean Association for the Study of Diabetes(EASD) as add-on treatment to metformin formanagement of hyperglycemia. 1 The positionstatement also stresses individualization oftherapy and highlights the need to consider anyestablished vascular complications that may bepresent in those with type 2 diabetes, as there isincreased risk for CV morbidity and mortality inthis population. 1 This meta-analysis from Patil andcolleagues provides insights into the effects ofDPP-4 inhibitors on cardiovascular (CV) events,and is the fi rst adequately powered study thatshows a class-wide effect for DPP-4 inhibitorsin decreasing CV event risk over long-termtreatment (≥24 weeks).DPP-4 inhibitor therapy demonstrated a similarrisk of adverse events when compared withplacebo, but showed a signifi cantly lower riskwhen compared with metformin, sulfonylureas,and thiazolidinediones. Longer studies includedin the analysis (≥52 weeks’ duration) also showeddecreased risk of the primary endpoint vs controltreatment.*Defi ned as death from CV causes, nonfatal myocardialinfarction or acute coronary syndrome, stroke andarrhythmias, and heart failure.1. Inzucchi SE, Bergenstal RM, Buse JB, et al.Management of hyperglycemia in type 2 diabetes:a patient-centered approach: position statement ofthe American Diabetes Association (ADA) and theEuropean Association for the Study of Diabetes (EASD).Diabetes Care. 2012;35(6):1364-1379.Visit for more onthe ADA/EASD PositionStatement on Management ofHyperglycemia in Type 2Diabetes: click the ClinicalGuideline link in the leftnavigation on the NDEI.orghomepage.Studies included in the meta-analysis (18 trials;N=8,544) were randomized, controlled trialscomparing treatment with DPP-4 inhibitors(n=4,998) to another oral antihyperglycemicagent (n=3,546) for ≥24 weeks (median treatmentduration: 46.4 weeks). Studies also included dataregarding adverse CV outcomes associated withuse of DPP-4 therapy. Development of adverseCV events* was the primary endpoint.Results:When compared with placebo or other oralantihyperglycemic agents, use of DPP-4 inhibitorsconferred:• Lower risk of adverse CV events: relative risk(RR), 0.48 (95% confi dence interval [CI],0.31-0.75; P=0.001)• Lower risk of nonfatal myocardial infarctionor acute coronary syndrome: RR, 0.40(95% CI, 0.18-0.88; P=0.02)Patil HR, Al Badarin FJ, Al Shami HA, et al. Metaanalysisof effect of dipeptidyl peptidase-4 inhibitors oncardiovascular risk in type 2 diabetes mellitus. Am JCardiol. 2012;110:826-833.More on DPP-4 Inhibitorsfor Type 2 DiabetesKaragiannis and colleagues conducted asystematic review and meta-analysis of27 studies to evaluate the effi cacy ofDPP-4 inhibitors for treatment of type 2diabetes when compared with otherantihyperglycemic therapies.To learn more about the results of thisstudy, download the May 2012 issue ofClinical Insights ® in Diabetes!Visit often for the latest diabetes data! Recent content updates:• Interactive case study: Silvio Inzucchi, MD, offers clinical perspectives in the case of a58-year-old man with uncontrolled type 2 diabetes and history of CVD using concepts from theADA/EASD hyperglycemia guideline. Click the On-Demand Programs > Case Studies link in theleft navigation on the homepage to view.• ADA and American Geriatrics Society guideline for managing type 2 diabetes in olderadults: We’ve distilled this new consensus report for you! Explore the key clinical messages inour reference chart and slides. Click the Clinical Guidelines link in in the left navigation on homepage to view.• Patient education handouts that you can use in your practice: Our most recent handoutscover topics including lifestyle changes, hypertension, medications used to treat diabetes, andmore. Click the Patient Education link in the left navigation on the homepage to view.Plus, coming soon, a new issue of Clinical Insights ® in Diabetes!KnowledgePoint360 Group, LLC125 Chubb AvenueLyndhurst, NJ 07071pg 7

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