Background Rosiglitazone is widely used to treat patients withtype 2 diabetes mellitus, but its effect on cardiovascular morbidityand mortality has not been determined.
Methods We conducted searches of the published literature, theWeb site of the Food and Drug Administration, and a clinical-trialsregistry maintained by the drug manufacturer (GlaxoSmithKline).Criteria for inclusion in our meta-analysis included a studyduration of more than 24 weeks, the use of a randomized controlgroup not receiving rosiglitazone, and the availability of outcomedata for myocardial infarction and death from cardiovascularcauses. Of 116 potentially relevant studies, 42 trials met theinclusion criteria. We tabulated all occurrences of myocardialinfarction and death from cardiovascular causes.
Results Data were combined by means of a fixed-effects model.In the 42 trials, the mean age of the subjects was approximately56 years, and the mean baseline glycated hemoglobin level wasapproximately 8.2%. In the rosiglitazone group, as comparedwith the control group, the odds ratio for myocardial infarctionwas 1.43 (95% confidence interval [CI], 1.03 to 1.98; P=0.03),and the odds ratio for death from cardiovascular causes was1.64 (95% CI, 0.98 to 2.74; P=0.06).
Conclusions Rosiglitazone was associated with a significantincrease in the risk of myocardial infarction and with an increasein the risk of death from cardiovascular causes that had borderlinesignificance. Our study was limited by a lack of access to originalsource data, which would have enabled time-to-event analysis.Despite these limitations, patients and providers should considerthe potential for serious adverse cardiovascular effects oftreatment with rosiglitazone for type 2 diabetes.
Thiazolidinedione drugs are widely used to lower blood glucoselevels in patients with type 2 diabetes mellitus. In the UnitedStates, three such agents have been introduced: troglitazone,which was removed from the market because of hepatotoxicity,and two currently available agents, rosiglitazone (Avandia,GlaxoSmithKline) and pioglitazone (Actos, Takeda). The thiazolidinedionesare agonists for peroxisome-proliferator–activated receptor (PPAR-). PPAR- receptors are ligand-activated nuclear transcriptionfactors that modulate gene expression, lowering blood glucoseprimarily by increasing insulin sensitivity in peripheral tissues.1,2Rosiglitazone was introduced in 1999 and is widely used as monotherapyor in fixed-dose combinations with either metformin (Avandamet,GlaxoSmithKline) or glimepiride (Avandaryl, GlaxoSmithKline).
The original approval of rosiglitazone was based on the abilityof the drug to reduce blood glucose and glycated hemoglobinlevels.3 Initial studies were not adequately powered to determinethe effects of this agent on microvascular or macrovascularcomplications of diabetes, including cardiovascular morbidityand mortality.3 However, the effect of any antidiabetic therapyon cardiovascular outcomes is particularly important, becausemore than 65% of deaths in patients with diabetes are from cardiovascularcauses.4 Therefore, we performed a meta-analysis of trials comparingrosiglitazone with placebo or active comparators to assess theeffect of this agent on cardiovascular outcomes. The sourcematerial for this analysis consisted of publicly available datafrom the original registration package submitted to the Foodand Drug Administration (FDA), another series of trials performedby the sponsor after approval, and two large, prospective, randomizedtrials designed to study additional indications for the drug.
Methods
Analyzed Studies
Table 1 lists the 42 trials included in this meta-analysis.We screened 116 phase 2, 3, and 4 trials for inclusion. Of these,48 trials met the predefined inclusion criteria of having arandomized comparator group, a similar duration of treatmentin all groups, and more than 24 weeks of drug exposure. Sixof the 48 trials did not report any myocardial infarctions ordeaths from cardiovascular causes and therefore were not includedin the analysis because the effect measure could not be calculated.Of the remaining 42 studies, 38 reported at least one myocardialinfarction, and 23 reported at least one death from cardiovascularcauses. In these trials, 15,565 patients were randomly assignedto regimens that included rosiglitazone, and 12,282 were assignedto comparator groups with regimens that did not include rosiglitazone.
Table 1. Clinical Trials of Rosiglitazone in the Meta-Analysis.
Multiple groups of patients who received rosiglitazone withina single trial were pooled together, when applicable. The controlgroup was defined as patients receiving any drug regimen otherthan rosiglitazone. The trials fall into three categories. Onegroup includes five of the studies submitted to the FDA forthe March 22, 1999, advisory board hearing that recommendedapproval of rosiglitazone. Group-level data from these fivestudies are available in publicly disclosed briefing documentsarchived on the FDA Web site.6 Data from these same trials arealso reported in a summary fashion on a clinical-trial registryWeb site maintained by the drug manufacturer, GlaxoSmithKline.5Reports of four of these five trials were also published inpeer-reviewed journals.7,8,9 In these five trials, 1967 patientswere randomly assigned to receive rosiglitazone, and 793 patientswere assigned to receive various comparator drugs (Table 1).
Other studies that we included in the meta-analysis were initiallyidentified in the GlaxoSmithKline clinical-trial registry.5As noted in Table 1, we included 35 studies in this category,9 of which were published in peer-reviewed journals and 26 ofwhich remain unpublished.10,11,12,13,14,15,16,17,18 Wheneverpossible, the results obtained on the GlaxoSmithKline Web sitewere cross-checked with the publication. In cases of disagreementbetween published and unpublished data, data derived from themanufacturer's Web site were used. In this group of 35 trials,9507 patients were randomly assigned to receive rosiglitazone,and 5960 patients were assigned to receive various comparatordrugs.
A third data source consisted of two large, recently publishedtrials, the Diabetes Reduction Assessment with Ramipiril andRosiglitazone Medication (DREAM) NCT00095654
[ClinicalTrials.gov]
trial20 and theA Diabetes Outcome Prevention Trial (ADOPT) (ClinicalTrials.govnumber, NCT00279045
[ClinicalTrials.gov]
).21 In the DREAM study, 2635 patients wererandomly assigned to receive rosiglitazone and 2634 patientswere assigned to receive placebo. The DREAM study was designedto determine whether rosiglitazone could prevent the developmentof type 2 diabetes in patients at high risk for this disorder.In the ADOPT trial, 1456 patients were randomly assigned toreceive rosiglitazone and 2895 patients were assigned to receiveeither metformin or glyburide. The ADOPT study was designedto assess the durability of glycemic control with rosiglitazonetherapy, as compared with therapy with metformin or glyburide.
Outcome Measures
We reviewed data summaries provided in the FDA review documents,the GlaxoSmithKline clinical-trial registry Web site, and publishedtrial results and then abstracted from the adverse-event tabulationsinformation on myocardial infarction and death from cardiovascularcauses. With the exception of the DREAM study, the includedtrials did not describe adjudication of myocardial infarctionor death from cardiovascular causes. Time-to-event data forcardiovascular events were not available in any of these trials,which precluded the calculation of hazard ratios. Because onlysummary data were available, it was not possible to discernwhether the same patient had both events. Therefore, an outcomemeasure based on the composite of death or myocardial infarctioncould not be constructed. Accordingly, these two outcomes arereported separately.
Statistical Analysis
Many trials had few cardiovascular events, so the odds ratiosand 95% confidence intervals were calculated with the use ofthe Peto method.22,23,24 Because all trials had similar durationsof follow-up for all treatment groups, the use of odds ratiosrepresents a valid approach to assessing the risk associatedwith the use of rosiglitazone. Trials in which patients hadno adverse cardiovascular events in either group were excludedfrom analyses. All reported P values are two-sided. Statisticalheterogeneity across the various trials was tested with theuse of Cochran's Q statistic. A P value of more than the nominallevel of 0.10 for the Q statistic indicated a lack of heterogeneityacross trials, allowing for the use of a fixed-effects model.For additional analyses, the active comparator control groupswere subgrouped into the following four classes for comparisonwith rosiglitazone: metformin, sulfonylurea, insulin, and placebo.Odds ratios and 95% confidence intervals were calculated foreach subgroup with the use of methods similar to those usedin the pooled analyses. Data were analyzed with the use of ComprehensiveMeta-Analysis software, version 2.2 (Biostat).
Results
Baseline Characteristics
Table 2 reports the doses of rosiglitazone and comparator drugs,baseline demographic characteristics, study periods, and glycatedhemoglobin levels or fasting blood glucose levels for patientsenrolled in the trials. The patients were relatively young,averaging less than 57 years of age for both the rosiglitazonegroup and the control group. Overall, there was a moderate predominanceof men. Diabetes control was relatively poor, with a mean baselineglycated hemoglobin level of approximately 8.2% for both studygroups.
Table 2. Doses, Baseline Demographic Characteristics, Study Periods, and Glycated Hemoglobin Levels.
Myocardial Infarction and Death
Table 3 reports the myocardial infarction events and deathsfrom cardiovascular causes that were reported in the 42 clinicaltrials we reviewed. There were 86 myocardial infarctions inthe rosiglitazone group and 72 in the control group. There were39 deaths from cardiovascular causes in the rosiglitazone groupand 22 in the control group. Table 4 lists the odds ratios,95% confidence intervals, and P values for myocardial infarctionand death from cardiovascular causes for the rosiglitazone groupand the control group. The summary odds ratio for myocardialinfarction was 1.43 in the rosiglitazone group (95% confidenceinterval [CI], 1.03 to 1.98; P=0.03). The odds ratio for deathfrom cardiovascular causes in the rosiglitazone group, as comparedwith the control group, was 1.64 (95% CI, 0.98 to 2.74; P=0.06).Table 4 also lists odds ratios and 95% confidence intervalsfor the pooled group of trials that were smaller and of shorterduration; results for the DREAM and ADOPT studies are shownseparately.
Table 4. Rates of Myocardial Infarction and Death from Cardiovascular Causes.
Table 5 lists odds ratios for myocardial infarction and deathfrom cardiovascular causes associated with rosiglitazone forsubgroups defined according to the comparator drug. Similarresults were obtained when the analysis excluded trials withan active comparator group. The heterogeneity P values were0.53 for myocardial infarction and 0.68 for death from cardiovascularcauses across subgroups. As compared with placebo or other antidiabeticregimens, the estimated odds ratios in all cases were greaterthan 1.0, suggesting that observed adverse effects during rosiglitazonetreatment were not unique to any specific comparator regimen.
Table 5. Risk of Myocardial Infarction and Death from Cardiovascular Causes for Patients Receiving Rosiglitazone versus Several Comparator Drugs.
In an analysis that was not prespecified, we also studied theeffects of rosiglitazone on death from any cause. The odds ratiofor death from any cause was 1.18 (95% CI, 0.89 to 1.55; P=0.24).
Discussion
Our data show that, as compared with placebo or with other antidiabeticregimens, treatment with rosiglitazone was associated with asignificant increase in the risk of myocardial infarction andwith an increase in the risk of death from cardiovascular causesthat was of borderline significance. The similar odds ratiofor comparison with placebo suggests that the increased riskassociated with rosiglitazone was not a function of the protectiveeffects of active comparator drugs. However, these findingsare based on limited access to trial results from publicly availablesources, not on patient-level source data. Furthermore, resultsare based on a relatively small number of events, resultingin odds ratios that could be affected by small changes in theclassification of events. Nonetheless, our findings are worrisomebecause of the high incidence of cardiovascular events in patientswith diabetes.4 Because exposure of such patients to rosiglitazoneis widespread, the public health impact of an increase in cardiovascularrisk could be substantial if our data are borne out by furtheranalysis and the results of larger controlled trials.
Although we did not have access to the source data to constructa composite outcome that included myocardial infarction or deathfrom cardiovascular causes, the increase in the odds ratiosfor both of these end points suggests that observed adverseeffects associated with rosiglitazone were probably not dueto chance alone. This meta-analysis included a group of trialsthat were of relatively short duration (24 to 52 weeks). Theodds ratio for these shorter-term trials was similar to theoverall results of the meta-analysis. Thus, in susceptible patients,rosiglitazone therapy may be capable of provoking myocardialinfarction or death from cardiovascular causes after relativelyshort-term exposure. In contrast, long-term therapies that improvecardiovascular outcomes, such as statins and antihypertensivedrugs, often take several years to provide benefits. Notably,the estimates for the odds ratios for myocardial infarctionand death from cardiovascular causes appear elevated for rosiglitazonein comparison with placebo or other commonly prescribed antidiabetictherapies (Table 5).
The mechanism for the apparent increase in myocardial infarctionand death from cardiovascular causes associated with rosiglitazoneremains uncertain. One potential contributing factor may bethe adverse effect of the drug on serum lipids. The FDA-approvedrosiglitazone product label reports a mean increase in low-densitylipoprotein (LDL) cholesterol of 18.6% among patients treatedfor 26 weeks with an 8-mg daily dose, as compared with placebo.25In observational studies and lipid-lowering trials, elevatedlevels of LDL cholesterol were associated with an increase inadverse cardiovascular outcomes. Thus, an increase in LDL cholesterolof the magnitude observed in the rosiglitazone group may havecontributed to adverse cardiovascular outcomes, although therapidity and magnitude of the apparent hazard was not consistentwith an effect produced by lipid changes alone.
Several other properties of rosiglitazone may contribute toadverse cardiovascular outcomes. Rosiglitazone and other thiazolidinedionesare known to precipitate congestive heart failure in susceptiblepatients.26 Congestive heart failure is a physiological statethat is associated with an increased intravascular volume. Volumeoverload increases stress on the left ventricular wall, a factorthat determines myocardial oxygen demand. In susceptible patients,an increase in myocardial oxygen demand could theoreticallyprovoke ischemic events. The administration of thiazolidinediones,including rosiglitazone, also produces a modest reduction inthe hemoglobin level.25 In susceptible patients, a reduced hemoglobinlevel may result in increased physiological stress, therebyprovoking myocardial ischemia. A study of rosiglitazone thatwas conducted in rats reported an increase in the rate of deathafter experimentally induced myocardial infarction.27
Rosiglitazone is not the first PPAR agonist that has been reportedto increase adverse cardiovascular events. Muraglitazar, aninvestigational dual PPAR- and PPAR- agonist, increased adversecardiovascular events, including myocardial infarction, duringphase 2 and 3 testing.28 After publication of an analysis ofcardiovascular outcomes, muraglitazar was not approved by theFDA, and further development was subsequently halted by themanufacturer. Development programs for many other PPAR agonistshave been terminated after evidence of toxicity emerged duringpreclinical studies or initial trials in humans. According toa former FDA official, more than 50 Investigational New Drugapplications for novel PPARs have been filed, but no additionaldrugs have successfully reached the market in more than 6 years.29In some cases, these drugs have failed because of evidence ofdirect myocardial toxicity in studies in animals,29 but fewdata on toxicity are available in the public domain becauseof the common industry practice of not publishing safety findingsfor failed products.
PPAR agonists such as rosiglitazone have very complex biologiceffects, resulting from the activation or suppression of dozensof genes.30 The patterns of gene activation or suppression differsubstantially among various PPAR agonists, even within closelyrelated compounds. The biologic effects of the protein targetsfor most of the genes influenced by PPAR agonists remain largelyunknown. Accordingly, many different and seemingly unrelatedtoxic effects have emerged during development of other PPARagents.29 Some drugs have provoked multispecies, multi–organsystem cancers; others have resulted in rhabdomyolysis or nephrotoxicity.29Troglitazone was withdrawn from the market for rare, but sometimesfatal, liver toxicity. Accordingly, it must be assumed thata variety of unexpected toxic effects are possible when PPARagonists are administered to patients.
The question as to whether the observed risks of rosiglitazonerepresent a "class effect" of thiazolidinediones must also beconsidered. Pioglitazone is a related agent also widely usedto treat type 2 diabetes mellitus. However, unlike rosiglitazone,pioglitazone has been studied in a prospective, randomized trialof cardiovascular outcomes, called Prospective PioglitazoneClinical Trial in Macrovascular Events (PROACTIVE).31 The primaryend point, a broad composite that included coronary and peripheralvascular events, showed a trend toward benefit from pioglitazone(hazard ratio, 0.90; P=0.095). A secondary end point consistingof myocardial infarction, stroke, and death from any cause showeda significant effect favoring pioglitazone (hazard ratio, 0.84;P=0.027). Notably, pioglitazone appears to have more favorableeffects on lipids, particularly triglycerides, than does rosiglitazone.32
These emerging findings raise an important question about theappropriateness of the current regulatory pathways for the developmentof drugs to treat diabetes. The FDA considers demonstrationof a sustained reduction in blood glucose levels with an acceptablesafety profile adequate for approval of antidiabetic agents.However, the ultimate value of antidiabetic therapy is the reductionof the complications of diabetes, not improvement in a laboratorymeasure of glycemic control. Although reductions in blood glucoselevels have been shown to reliably reduce microvascular complicationsof diabetes, the effect on macrovascular complications has provedto be unpredictable.33 After the failure of muraglitazar andthe apparent increase in adverse cardiovascular outcomes withrosiglitazone, the use of blood glucose measurements as a surrogateend point in regulatory approval must be carefully reexamined.
Our study has important limitations. We pooled the results ofa group of trials that were not originally intended to explorecardiovascular outcomes. Most trials did not centrally adjudicatecardiovascular outcomes, and the definitions of myocardial infarctionwere not available. Many of these trials were small and short-term,resulting in few adverse cardiovascular events or deaths. Accordingly,the confidence intervals for the odds ratios for myocardialinfarction and death from cardiovascular causes are wide, resultingin considerable uncertainty about the magnitude of the observedhazard. Furthermore, we did not have access to original sourcedata for any of these trials. Thus, we based the analysis onavailable data from publicly disclosed summaries of events.The lack of availability of source data did not allow the useof more statistically powerful time-to-event analysis. A meta-analysisis always considered less convincing than a large prospectivetrial designed to assess the outcome of interest. Although sucha dedicated trial has not been completed for rosiglitazone,the ongoing Rosiglitazone Evaluated for Cardiac Outcomes andRegulation of Glycaemia in Diabetes (RECORD) trial may provideuseful insights.34
Despite these limitations, our data point to the urgent needfor comprehensive evaluations to clarify the cardiovascularrisks of rosiglitazone. The manufacturer's public disclosureof summary results for rosiglitazone clinical trials is notsufficient to enable a robust assessment of cardiovascular risks.The manufacturer has all the source data for completed clinicaltrials and should make these data available to an external academiccoordinating center for systematic analysis. The FDA also hasaccess to study reports and other clinical-trial data not withinthe public domain. Further analyses of data available to theFDA and the manufacturer would enable a more robust assessmentof the risks of this drug. Our data suggest a cardiovascularrisk associated with the use of rosiglitazone. Until more preciseestimates of the cardiovascular risk of this treatment can bedelineated in patients with diabetes, patients and providersshould carefully consider the potential risks of rosiglitazonein the treatment of type 2 diabetes.
Dr. Nissen reports receiving research support to perform clinicaltrials through the Cleveland Clinic Cardiovascular CoordinatingCenter from Pfizer, AstraZeneca, Daiichi Sankyo, Roche, Takeda,Sanofi-Aventis, and Eli Lilly. Dr. Nissen consults for manypharmaceutical companies but requires them to donate all honorariaor consulting fees directly to charity so that he receives neitherincome nor a tax deduction. No other potential conflict of interestrelevant to this article was reported.
We thank Craig Balog for statistical programming support.
Source Information
From the Cleveland Clinic, Cleveland. This article (10.1056/NEJMoa072761) was published at www.nejm.org on May 21, 2007.
Address reprint requests to Dr. Nissen at the Department of Cardiovascular Medicine, Cleveland Clinic, 9500 Euclid Ave., Cleveland, OH 44195, or at nissens{at}ccf.org.
References
Vamecq J, Latruffe N. Medical significance of peroxisome proliferator-activated receptors. Lancet 1999;354:141-148. [CrossRef][Web of Science][Medline]
Center for Drug Evaulation and Research. Approval package: Avandia (rosiglitazone maleate) tablets. Company: SmithKline Beecham Pharmaceuticals. Application no. 21-071. Approval date: 5/25/1999. (Accessed May 18, 2007, at http://www.fda.gov/cder/foi/nda/99/21071_Avandia.htm.)
Lebovitz HE, Dole JF, Patwardhan R, Rappaport EB, Freed MI. Rosiglitazone monotherapy is effective in patients with type 2 diabetes. J Clin Endocrinol Metab 2001;86:280-288. [Erratum, J Clin Endocrinol Metab 2001;86:1659, 2002;2:iv.] [Free Full Text]
Phillips LS, Grunberger G, Miller E, et al. Once- and twice-daily dosing with rosiglitazone improves glycemic control in patients with type 2 diabetes. Diabetes Care 2001;24:308-315. [Erratum, Diabetes 2001;24:973.] [Free Full Text]
Jones TA, Sautter M, Van Gaal LF, Jones NP. Addition of rosiglitazone to metformin is most effective in obese, insulin-resistant patients with type 2 diabetes. Diabetes Obes Metab 2003;5:163-170. [CrossRef][Web of Science][Medline]
Fonseca V, Rosenstock J, Patwardhan R, Salzman A. Effect of metformin and rosiglitazone combination therapy in patients with type 2 diabetes mellitus: a randomized controlled trial. JAMA 2000;283:1695-1702. [Erratum, JAMA 2000;284:1384.] [Free Full Text]
Weissman P, Goldstein BJ, Rosenstock J, et al. Effects of rosiglitazone added to submaximal doses of metformin compared with dose escalation of metformin in type 2 diabetes: the EMPIRE Study. Curr Med Res Opin 2005;21:2029-2035. [CrossRef][Web of Science][Medline]
Wolffenbuttel BH, Gomis R, Squatrito S, Jones NP, Patwardhan RN. Addition of low-dose rosiglitazone to sulphonylurea therapy improves glycaemic control in Type 2 diabetic patients. Diabet Med 2000;17:40-47. [CrossRef][Web of Science][Medline]
St John Sutton M, Rendell M, Dandona P, et al. A comparison of the effects of rosiglitazone and glyburide on cardiovascular function and glycemic control in patients with type 2 diabetes. Diabetes Care 2002;25:2058-2064. [Free Full Text]
Raskin P, Rendell M, Riddle MC, et al. A randomized trial of rosiglitazone therapy in patients with inadequately controlled insulin-treated type 2 diabetes. Diabetes Care 2001;24:1226-1232. [Free Full Text]
Vongthavaravat V, Wajchenberg BL, Waitman JN, et al. An international study of the effects of rosiglitazone plus sulphonylurea in patients with type 2 diabetes. Curr Med Res Opin 2002;18:456-461. [CrossRef][Web of Science][Medline]
Baksi A, James RE, Zhou B, Nolan JJ. Comparison of uptitration of gliclazide with the addition of rosiglitazone to gliclazide in patients with type 2 diabetes inadequately controlled on half-maximal doses of a sulphonylurea. Acta Diabetol 2004;41:63-69. [Web of Science][Medline]
Barnett AH, Grant PJ, Hitman GA, et al. Rosiglitazone in Type 2 diabetes mellitus: an evaluation in British Indo-Asian patients. Diabet Med 2003;20:387-393. [CrossRef][Web of Science][Medline]
Kerenyi Z, Samer H, James R, Yan Y, Stewart M. Combination therapy with rosiglitazone and glibenclamide compared with upward titration of glibenclamide alone in patients with type 2 diabetes mellitus. Diabetes Res Clin Pract 2004;63:213-223. [CrossRef][Web of Science][Medline]
Zhu XX, Pan CY, Li GW, et al. Addition of rosiglitazone to existing sulfonylurea treatment in Chinese patients with type 2 diabetes and exposure to hepatitis B or C. Diabetes Technol Ther 2003;5:33-42. [CrossRef][Medline]
The DREAM (Diabetes Reduction Assessment with ramipril and rosiglitazone Medication) Investigators. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet 2006;368:1096-1105. [Erratum, Lancet 2006;368:1770.] [CrossRef][Medline]
Kahn SE, Haffner SM, Heise MA, et al. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med 2006;355:2427-2443. [Erratum, N Engl J Med 2007;356:1387-8.] [Free Full Text]
Bradburn MJ, Deeks JJ, Berlin JA, Localio AR. Much ado about nothing: a comparison of the performance of meta-analytical methods with rare events. Stat Med 2007;26:53-77. [CrossRef][Web of Science][Medline]
Sweeting MJ, Sutton AJ, Lambert PC. What to add to nothing? Use and avoidance of continuity corrections in meta-analysis of sparse data. Stat Med 2004;23:1351-1375. [Erratum, Stat Med 2006;25:2700.] [CrossRef][Web of Science][Medline]
Sutton A, Cooper N, Lambert P, Jones D, Abrams K, Sweeting M. Meta-analysis of rare and adverse event data. Pharmacoeconomics Outcomes Res 2002;2:367.
Nesto RW, Bell D, Bonow RO, et al. Thiazolidinedione use, fluid retention, and congestive heart failure: a consensus statement from the American Heart Association and American Diabetes Association: October 7, 2003. Circulation 2003;108:2941-2948. [Free Full Text]
Lygate CA, Hulbert K, Monfared M, Cole MA, Clarke K, Neubauer S. The PPARgamma-activator rosiglitazone does not alter remodeling but increases mortality in rats post-myocardial infarction. Cardiovasc Res 2003;58:632-637. [Free Full Text]
Nissen SE, Wolski K, Topol EJ. Effect of muraglitazar on death and major adverse cardiovascular events in patients with type 2 diabetes mellitus. JAMA 2005;294:2581-2586. [Free Full Text]
El-Hage J. Peroxisome proliferator-activated receptor (PPAR) agonists: preclinical and clinical cardiac safety considerations. Rockville, MD: Center for Drug Evaluation and Research, 2006. (Accessed May 18, 2007, at http://www.fda.gov/cder/present/DIA2006/El-Hage_CardiacSafety.ppt.)
Lemay DG, Hwang DH. Genome-wide identification of peroxisome proliferator response elements using integrated computational genomics. J Lipid Res 2006;47:1583-1587. [Free Full Text]
Dormandy JA, Charbonnel B, Eckland DJ, et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet 2005;366:1279-1289. [CrossRef][Web of Science][Medline]
Goldberg RB, Kendall DM, Deeg MA, et al. A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with type 2 diabetes and dyslipidemia. Diabetes Care 2005;28:1547-1554. [Free Full Text]
Riveline JP, Danchin N, Ledru F, Varroud-Vial M, Charpentier G. Sulfonylureas and cardiovascular effects: from experimental data to clinical use: available data in humans and clinical applications. Diabetes Metab 2003;29:207-222. [Web of Science][Medline]
Home PD, Pocock SJ, Beck-Nielsen H, et al. Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes (RECORD): study design and protocol. Diabetologia 2005;48:1726-1735. [CrossRef][Web of Science][Medline]
Philbrick, A. M., Ernst, M. E., McDanel, D. L., Ross, M. B., Moores, K. G.
(2009). Metformin use in renal dysfunction: Is a serum creatinine threshold appropriate?. Am J Health Syst Pharm
66: 2017-2022
[Abstract][Full Text]
Vedula, S. S., Bero, L., Scherer, R. W., Dickersin, K.
(2009). Outcome Reporting in Industry-Sponsored Trials of Gabapentin for Off-Label Use. NEJM
361: 1963-1971
[Abstract][Full Text]
Amoruso, A., Bardelli, C., Fresu, L. G., Palma, A., Vidali, M., Ferrero, V., Ribichini, F., Vassanelli, C., Brunelleschi, S.
(2009). Enhanced Peroxisome Proliferator-Activated Receptor-{gamma} Expression in Monocyte/Macrophages from Coronary Artery Disease Patients and Possible Gender Differences. J. Pharmacol. Exp. Ther.
331: 531-538
[Abstract][Full Text]
Bain, J. R., Stevens, R. D., Wenner, B. R., Ilkayeva, O., Muoio, D. M., Newgard, C. B.
(2009). Metabolomics Applied to Diabetes Research: Moving From Information to Knowledge. Diabetes
58: 2429-2443
[Full Text]
Nilsson, P. M.
(2009). Hypertension and Diabetes: Should We Treat Early Surrogates?: What are the cons?. Diabetes Care
32: S290-S293
[Full Text]
Kassem, S. A., Raz, I.
(2009). Is There Evidence That Oral Hypoglycemic Agents Reduce Cardiovascular Morbidity or Mortality? No. Diabetes Care
32: S337-S341
[Full Text]
Bianchi, C., Miccoli, R., Daniele, G., Penno, G., Del Prato, S.
(2009). Is There Evidence That Oral Hypoglycemic Agents Reduce Cardiovascular Morbidity/Mortality? Yes. Diabetes Care
32: S342-S348
[Full Text]
Kleinhenz, J. M., Kleinhenz, D. J., You, S., Ritzenthaler, J. D., Hansen, J. M., Archer, D. R., Sutliff, R. L., Hart, C. M.
(2009). Disruption of endothelial peroxisome proliferator-activated receptor-{gamma} reduces vascular nitric oxide production. Am. J. Physiol. Heart Circ. Physiol.
297: H1647-H1654
[Abstract][Full Text]
Koppen, A., Houtman, R., Pijnenburg, D., Jeninga, E. H., Ruijtenbeek, R., Kalkhoven, E.
(2009). Nuclear Receptor-Coregulator Interaction Profiling Identifies TRIP3 as a Novel Peroxisome Proliferator-activated Receptor {gamma} Cofactor. Mol. Cell. Proteomics
8: 2212-2226
[Abstract][Full Text]
Kavoussi, S.K., Witz, C.A., Binkley, P.A., Nair, A.S., Lebovic, D.I.
(2009). Peroxisome-proliferator activator receptor-gamma activation decreases attachment of endometrial cells to peritoneal mesothelial cells in an in vitro model of the early endometriotic lesion. Mol Hum Reprod
15: 687-692
[Abstract][Full Text]
Raj, S. R., Stein, C. M., Saavedra, P. J., Roden, D. M.
(2009). Cardiovascular Effects of Noncardiovascular Drugs. Circulation
120: 1123-1132
[Full Text]
Kelly, T. N., Bazzano, L. A., Fonseca, V. A., Thethi, T. K., Reynolds, K., He, J.
(2009). Systematic Review: Glucose Control and Cardiovascular Disease in Type 2 Diabetes. ANN INTERN MED
151: 394-403
[Abstract][Full Text]
Hirsch, L. J.
(2009). Conflicts of Interest, Authorship, and Disclosures in Industry-Related Scientific Publications: The Tort Bar and Editorial Oversight of Medical Journals. Mayo Clin Proc.
84: 811-821
[Full Text]
Yang, L., Xu, L., He, L.
(2009). A CitationRank algorithm inheriting Google technology designed to highlight genes responsible for serious adverse drug reaction. Bioinformatics
25: 2244-2250
[Abstract][Full Text]
Potenza, M. A., Gagliardi, S., De Benedictis, L., Zigrino, A., Tiravanti, E., Colantuono, G., Federici, A., Lorusso, L., Benagiano, V., Quon, M. J., Montagnani, M.
(2009). Treatment of spontaneously hypertensive rats with rosiglitazone ameliorates cardiovascular pathophysiology via antioxidant mechanisms in the vasculature. Am. J. Physiol. Endocrinol. Metab.
297: E685-E694
[Abstract][Full Text]
Yates, T, Davies, M, Khunti, K
(2009). Preventing type 2 diabetes: can we make the evidence work?. Postgrad. Med. J.
85: 475-480
[Abstract][Full Text]
Juurlink, D. N, Gomes, T., Lipscombe, L. L, Austin, P. C, Hux, J. E, Mamdani, M. M
(2009). Adverse cardiovascular events during treatment with pioglitazone and rosiglitazone: population based cohort study. BMJ
339: b2942-b2942
[Abstract][Full Text]
Xie, S., Lee, Y.-F., Kim, E., Chen, L.-M., Ni, J., Fang, L.-Y., Liu, S., Lin, S.-J., Abe, J.-i., Berk, B., Ho, F.-M., Chang, C.
(2009). TR4 nuclear receptor functions as a fatty acid sensor to modulate CD36 expression and foam cell formation. Proc. Natl. Acad. Sci. USA
106: 13353-13358
[Abstract][Full Text]
Rabkin, S. W., Lodha, P.
(2009). Stearic acid-induced cardiac lipotoxicity is independent of cellular lipid and is mitigated by the fatty acids oleic and capric acid but not by the PPAR agonist troglitazone. Exp Physiol
94: 877-887
[Abstract][Full Text]
Saraf, S., Nishtala, S., Parretti, H., Capps, N., Ramachandran, S.
(2009). Paradoxical fall in HDL cholesterol observed in a patient treated with rosiglitazone and pioglitazone. British Journal of Diabetes & Vascular Disease
9: 186-189
Chaggar, P. S., Shaw, S. M., Williams, S. G.
(2009). Review article: Thiazolidinediones and heart failure. Diabetes and Vascular Disease Research
6: 146-152
[Abstract]
Hemmingsen, B., Lund, S. S, Wetterslev, J., Vaag, A.
(2009). Oral hypoglycaemic agents, insulin resistance and cardiovascular disease in patients with type 2 diabetes. Eur J Endocrinol
161: 1-9
[Abstract][Full Text]
Yang, L., Luo, H., Chen, J., Xing, Q., He, L.
(2009). SePreSA: a server for the prediction of populations susceptible to serious adverse drug reactions implementing the methodology of a chemical-protein interactome. Nucleic Acids Res
37: W406-W412
[Abstract][Full Text]
Brooks, A. M., Thacker, S. M
(2009). Dapagliflozin for the Treatment of Type 2 Diabetes. The Annals of Pharmacotherapy
43: 1286-1293
[Abstract][Full Text]
Jones, A., Deb, R., Torsney, E., Howe, F., Dunkley, M., Gnaneswaran, Y., Gaze, D., Nasr, H., Loftus, I. M., Thompson, M. M., Cockerill, G. W.
(2009). Rosiglitazone Reduces the Development and Rupture of Experimental Aortic Aneurysms. Circulation
119: 3125-3132
[Abstract][Full Text]
Allen, L. A., Hernandez, A. F., O'Connor, C. M., Felker, G. M.
(2009). End points for clinical trials in acute heart failure syndromes.. J Am Coll Cardiol
53: 2248-2258
[Abstract][Full Text]
The BARI 2D Study Group,
(2009). A Randomized Trial of Therapies for Type 2 Diabetes and Coronary Artery Disease. NEJM
360: 2503-2515
[Abstract][Full Text]
Lonn, E. M., Gerstein, H. C., Sheridan, P., Smith, S., Diaz, R., Mohan, V., Bosch, J., Yusuf, S., Dagenais, G. R., DREAM (Diabetes REduction Assessment with ramipril,
(2009). Effect of Ramipril and of Rosiglitazone on Carotid Intima-Media Thickness in People With Impaired Glucose Tolerance or Impaired Fasting Glucose STARR (STudy of Atherosclerosis with Ramipril and Rosiglitazone).. J Am Coll Cardiol
53: 2028-2035
[Abstract][Full Text]
St. Onge, E. L., Miller, S. A., Taylor, J. R.
(2009). Novel Approaches to the Treatment of Type 2 Diabetes. Journal of Pharmacy Practice
22: 320-332
[Abstract]
Takagi, T., Okura, H., Kobayashi, Y., Kataoka, T., Taguchi, H., Toda, I., Tamita, K., Yamamuro, A., Sakanoue, Y., Ito, A., Yanagi, S., Shimeno, K., Waseda, K., Yamasaki, M., Fitzgerald, P. J., Ikeno, F., Honda, Y., Yoshiyama, M., Yoshikawa, J., for the POPPS Investigators,
(2009). A Prospective, Multicenter, Randomized Trial to Assess Efficacy of Pioglitazone on In-Stent Neointimal Suppression in Type 2 Diabetes: POPPS (Prevention of In-Stent Neointimal Proliferation by Pioglitazone Study). J Am Coll Cardiol Intv
2: 524-531
[Abstract][Full Text]
Nissen, S. E.
(2009). Pioglitazone to Reduce Restenosis After Bare-Metal Stent Placement?. J Am Coll Cardiol Intv
2: 532-533
[Full Text]
Hall, G. M., Nicholson, G.
(2009). Current Therapeutic Drugs for Type 2 Diabetes, Still Useful After 50 Years?. Anesth. Analg.
108: 1727-1730
[Full Text]
Nakaya, H., Summers, B. D., Nicholson, A. C., Gotto, A. M. Jr., Hajjar, D. P., Han, J.
(2009). Atherosclerosis in LDLR-Knockout Mice Is Inhibited, but Not Reversed, by the PPAR{gamma} Ligand Pioglitazone. Am. J. Pathol.
174: 2007-2014
[Abstract][Full Text]
Aronson, J.
(2009). When I Use a word ... Changing your practice. QJM
0: hcp055v1-hcp055
[Full Text]
Banarer, S., Luan, F. L., Duckworth, W. C., Moritz, T., Abraira, C.
(2009). Glucose Control and Vascular Complications in Type 2 Diabetes. NEJM
360: 2031-2032
[Full Text]
Gellad, W. F., Detsky, A. S., Choudhry, N. K.
(2009). Implications of recent clinical trials on pay-for-performance. Am J Health Syst Pharm
66: 864-867
[Full Text]
Nathan, D. M., for the American Diabetes Association and European,
(2009). Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy: A Consensus Statement of the American Diabetes Association and the European Association for the Study of Diabetes: Response to Cobitz and Ambery. Diabetes Care
32: e59-e59
[Full Text]
Ramirez, S. P.B., Albert, J. M., Blayney, M. J., Tentori, F., Goodkin, D. A., Wolfe, R. A., Young, E. W., Bailie, G. R., Pisoni, R. L., Port, F. K.
(2009). Rosiglitazone Is Associated with Mortality in Chronic Hemodialysis Patients. J. Am. Soc. Nephrol.
20: 1094-1101
[Abstract][Full Text]
Flaherty, M. L., Adeoye, O., Sekar, P., Haverbusch, M., Moomaw, C. J., Tao, H., Broderick, J. P., Woo, D.
(2009). The Challenge of Designing a Treatment Trial for Warfarin-Associated Intracerebral Hemorrhage. Stroke
40: 1738-1742
[Abstract][Full Text]
Brice, R.
(2009). A taxi driver with type 2 diabetes. BMJ
338: b1369-b1369
[Full Text]
Morrow, D. A., Scirica, B. M., Chaitman, B. R., McGuire, D. K., Murphy, S. A., Karwatowska-Prokopczuk, E., McCabe, C. H., Braunwald, E., for the MERLIN-TIMI 36 Investigators,
(2009). Evaluation of the Glycometabolic Effects of Ranolazine in Patients With and Without Diabetes Mellitus in the MERLIN-TIMI 36 Randomized Controlled Trial. Circulation
119: 2032-2039
[Abstract][Full Text]
Evans-Molina, C., Robbins, R. D., Kono, T., Tersey, S. A., Vestermark, G. L., Nunemaker, C. S., Garmey, J. C., Deering, T. G., Keller, S. R., Maier, B., Mirmira, R. G.
(2009). Peroxisome Proliferator-Activated Receptor {gamma} Activation Restores Islet Function in Diabetic Mice through Reduction of Endoplasmic Reticulum Stress and Maintenance of Euchromatin Structure. Mol. Cell. Biol.
29: 2053-2067
[Abstract][Full Text]
Vanasse, A., Carpentier, A. C., Courteau, J., Asghari, S.
(2009). Stroke and cardiovascular morbidity and mortality associated with rosiglitazone use in elderly diabetic patients. Diabetes and Vascular Disease Research
6: 87-93
[Abstract]
Olin, J. L., Spooner, L. M.
(2009). Introduction: Cardiovascular Therapeutics. Journal of Pharmacy Practice
22: 133-134
Cheng, J. W. M., Bhatt, S. H., Goldman-Levine, J. D.
(2009). The Benefit and Risk of Antidiabetic Agents Used in Patients With Heart Disease. Journal of Pharmacy Practice
22: 179-193
[Abstract]
Flory, J. H., Ellenberg, S., Szapary, P. O., Strom, B. L., Hennessy, S.
(2009). Antidiabetic Action of Bezafibrate in a Large Observational Database. Diabetes Care
32: 547-551
[Abstract][Full Text]
Meredith, D., Panchatcharam, M., Miriyala, S., Tsai, Y.-S., Morris, A. J., Maeda, N., Stouffer, G. A., Smyth, S. S.
(2009). Dominant-Negative Loss of PPAR{gamma} Function Enhances Smooth Muscle Cell Proliferation, Migration, and Vascular Remodeling. Arterioscler. Thromb. Vasc. Bio.
29: 465-471
[Abstract][Full Text]
Mathieu, P., Poirier, P., Pibarot, P., Lemieux, I., Despres, J.-P.
(2009). Visceral Obesity: The Link Among Inflammation, Hypertension, and Cardiovascular Disease. Hypertension
53: 577-584
[Full Text]
Campbell, I. W
(2009). Review: Durable glycaemia -- the promised land. British Journal of Diabetes & Vascular Disease
9: 53-63
[Abstract]
Song, S. H, Gray, T. A
(2009). Management of type 2 diabetes and lipids: a critique of the NICE guidelines 2008. British Journal of Diabetes & Vascular Disease
9: 69-74
[Abstract]
Koh, K. K., Oh, P. C., Quon, M. J.
(2009). Does reversal of oxidative stress and inflammation provide vascular protection?. Cardiovasc Res
81: 649-659
[Abstract][Full Text]
Wood, A. J.J.
(2009). Progress and Deficiencies in the Registration of Clinical Trials. NEJM
360: 824-830
[Full Text]
Horton, E. S.
(2009). Defining the role of basal and prandial insulin for optimal glycemic control.. J Am Coll Cardiol
53: S21-S27
[Abstract][Full Text]
HOOGWERF, B. J.
(2009). IN REPLY:. Cleveland Clinic Journal of Medicine
76: 83-84
[Full Text]
Haneda, M., Morikawa, A.
(2009). Which hypoglycaemic agents to use in type 2 diabetic subjects with CKD and how?. Nephrol Dial Transplant
24: 338-341
[Full Text]
Havas, S.
(2009). The ACCORD Trial and Control of Blood Glucose Level in Type 2 Diabetes Mellitus: Time to Challenge Conventional Wisdom. Arch Intern Med
169: 150-154
[Full Text]
Loke, Y. K. MBBS MD, Singh, S. MD MPH, Furberg, C. D. MD PhD
(2009). Long-term use of thiazolidinediones and fractures in type 2 diabetes: a meta-analysis. CMAJ
180: 32-39
[Abstract][Full Text]
Lipscombe, L. L. MD MSc
(2009). Thiazolidinediones: Do harms outweigh benefits?. CMAJ
180: 16-17
[Full Text]
Lindsey, J. B, Cipollone, F., Abdullah, S. M, Mcguire, D. K
(2009). Receptor for advanced glycation end-products (RAGE) and soluble RAGE (sRAGE): cardiovascular implications. Diabetes and Vascular Disease Research
6: 7-14
[Abstract]
van Hooland, S., Boey, O., Van der Niepen, P., Van den Branden, C., Verbeelen, D.
(2009). Effect of Short-Term Rosiglitazone Therapy in Peritoneal Dialysis Patients. pdi
29: 108-111
[Full Text]
Nathan, D. M., Buse, J. B., Davidson, M. B., Ferrannini, E., Holman, R. R., Sherwin, R., Zinman, B.
(2009). Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy: A consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Clin. Diabetes
27: 4-16
[Full Text]
Nathan, D. M., Buse, J. B., Davidson, M. B., Ferrannini, E., Holman, R. R., Sherwin, R., Zinman, B.
(2009). Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy: A consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Spectr.
22: 6-17
[Full Text]
Ondrey, F.
(2009). Peroxisome Proliferator-Activated Receptor {gamma} Pathway Targeting in Carcinogenesis: Implications for Chemoprevention. Clin. Cancer Res.
15: 2-8
[Abstract][Full Text]
Joy, M. S., Gipson, D. S., Dike, M., Powell, L., Thompson, A., Vento, S., Eddy, A., Fogo, A. B., Kopp, J. B., Cattran, D., Trachtman, H.
(2009). Phase I Trial of Rosiglitazone in FSGS: I. Report of the FONT Study Group. CJASN
4: 39-47
[Abstract][Full Text]
Nathan, D. M., Buse, J. B., Davidson, M. B., Ferrannini, E., Holman, R. R., Sherwin, R., Zinman, B.
(2009). Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy: A consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care
32: 193-203
[Abstract][Full Text]
Jenkins, D. J. A., Kendall, C. W. C., McKeown-Eyssen, G., Josse, R. G., Silverberg, J., Booth, G. L., Vidgen, E., Josse, A. R., Nguyen, T. H., Corrigan, S., Banach, M. S., Ares, S., Mitchell, S., Emam, A., Augustin, L. S. A., Parker, T. L., Leiter, L. A.
(2008). Effect of a Low-Glycemic Index or a High-Cereal Fiber Diet on Type 2 Diabetes: A Randomized Trial. JAMA
300: 2742-2753
[Abstract][Full Text]
Michaelson, J.
(2008). Thiazolidinedione associated volume overload and pulmonary hypertension. Ther Adv Cardiovasc Dis
2: 435-438
[Abstract]
Cornier, M.-A., Dabelea, D., Hernandez, T. L., Lindstrom, R. C., Steig, A. J., Stob, N. R., Van Pelt, R. E., Wang, H., Eckel, R. H.
(2008). The Metabolic Syndrome. Endocr. Rev.
29: 777-822
[Abstract][Full Text]
Beysen, C., Murphy, E. J., Nagaraja, H., Decaris, M., Riiff, T., Fong, A., Hellerstein, M. K., Boyle, P. J.
(2008). A pilot study of the effects of pioglitazone and rosiglitazone on de novo lipogenesis in type 2 diabetes. J. Lipid Res.
49: 2657-2663
[Abstract][Full Text]
Winkelmayer, W. C., Setoguchi, S., Levin, R., Solomon, D. H.
(2008). Comparison of Cardiovascular Outcomes in Elderly Patients With Diabetes Who Initiated Rosiglitazone vs Pioglitazone Therapy. Arch Intern Med
168: 2368-2375
[Abstract][Full Text]
Von Bibra, H., Diamant, M., Scheffer, P. G, Siegmund, T., Schumm-Draeger, P.-M.
(2008). Rosiglitazone, but not glimepiride, improves myocardial diastolic function in association with reduction in oxidative stress in type 2 diabetic patients without overt heart disease. Diabetes and Vascular Disease Research
5: 310-318
[Abstract]
Shah, A., Mehta, N., Reilly, M. P.
(2008). Adipose Inflammation, Insulin Resistance, and Cardiovascular Disease. JPEN J Parenter Enteral Nutr
32: 638-644
[Abstract][Full Text]
Chitturi, S.
(2008). Review: Treatment options for nonalcoholic fatty liver disease. Therapeutic Advances in Gastroenterology
1: 173-189
[Abstract]
Hausenloy, D J, Yellon, D M
(2008). Targeting residual cardiovascular risk: raising high-density lipoprotein cholesterol levels. Postgrad. Med. J.
84: 590-598
[Abstract][Full Text]
Pinelli, N. R, Cha, R., Brown, M. B, Jaber, L. A
(2008). Addition of Thiazolidinedione or Exenatide to Oral Agents in Type 2 Diabetes: A Meta-Analysis. The Annals of Pharmacotherapy
42: 1541-1551
[Abstract][Full Text]
Nathan, D. M.
(2008). Glycemic Management of Type 2 Diabetes: How Tight Is Right and How to Get There. Arch Intern Med
168: 2064-2066
[Full Text]
Selvin, E., Bolen, S., Yeh, H.-C., Wiley, C., Wilson, L. M., Marinopoulos, S. S., Feldman, L., Vassy, J., Wilson, R., Bass, E. B., Brancati, F. L.
(2008). Cardiovascular Outcomes in Trials of Oral Diabetes Medications: A Systematic Review. Arch Intern Med
168: 2070-2080
[Abstract][Full Text]
Alexander, G. C., Sehgal, N. L., Moloney, R. M., Stafford, R. S.
(2008). National Trends in Treatment of Type 2 Diabetes Mellitus, 1994-2007. Arch Intern Med
168: 2088-2094
[Abstract][Full Text]
Ho, P. M., Peterson, P. N., Masoudi, F. A.
(2008). Evaluating the Evidence: Is There a Rigid Hierarchy?. Circulation
118: 1675-1684
[Full Text]
Jenny-Avital, E. R., Luan, F. L., Nguyen, K., Tobey, T. A., Parashar, A., Byington, R. P., Gerstein, H. C., Friedewald, W. T., Patel, A., MacMahon, S., Chalmers, J.
(2008). Intensive Glucose Control in Type 2 Diabetes. NEJM
359: 1519-1521
[Full Text]
HOOGWERF, B. J.
(2008). Does intensive therapy of type 2 diabetes help or harm? Seeking accord on ACCORD. Cleveland Clinic Journal of Medicine
75: 729-737
[Abstract][Full Text]
Odom, J., Williamson, B., Carter, L.
(2008). Rosiglitazone and pioglitazone in the treatment of diabetes mellitus. Am J Health Syst Pharm
65: 1846-1850
[Full Text]
Mallewa, J. E., Wilkins, E., Vilar, J., Mallewa, M., Doran, D., Back, D., Pirmohamed, M.
(2008). HIV-associated lipodystrophy: a review of underlying mechanisms and therapeutic options. J Antimicrob Chemother
62: 648-660
[Abstract][Full Text]
Johnson, E. L., Brosseau, J. D., Soule, M., Kolberg, J.
(2008). Treatment of Diabetes in Long-Term Care Facilities: A Primary Care Approach. Clin. Diabetes
26: 152-156
[Abstract][Full Text]
Rosenzweig, J. L., Ferrannini, E., Grundy, S. M., Haffner, S. M., Heine, R. J., Horton, E. S., Kawamori, R.
(2008). Primary Prevention of Cardiovascular Disease and Type 2 Diabetes in Patients at Metabolic Risk: An Endocrine Society Clinical Practice Guideline. J. Clin. Endocrinol. Metab.
93: 3671-3689
[Abstract][Full Text]
Kahn, S. E., Cefalu, W. T.
(2008). Glucose Control, Macro- and Microvascular Disease, and the Food and Drug Administration: Let's Keep Our Eye on the Ball. J. Clin. Endocrinol. Metab.
93: 3727-3729
[Full Text]
Srinivasan, B T, Jarvis, J, Khunti, K, Davies, M J
(2008). Recent advances in the management of type 2 diabetes mellitus: a review. Postgrad. Med. J.
84: 524-531
[Abstract][Full Text]
Khanderia, U., Pop-Busui, R., Eagle, K. A
(2008). Thiazolidinediones in Type 2 Diabetes: A Cardiology Perspective. The Annals of Pharmacotherapy
42: 1466-1474
[Abstract][Full Text]
Kittisupamongkol, W.
(2008). Effect of Folic Acid and B Vitamins on Cardiovascular Disease in Women. JAMA
300: 1410-1410
[Full Text]
Nallamothu, B. K., Hayward, R. A., Bates, E. R.
(2008). Beyond the Randomized Clinical Trial: The Role of Effectiveness Studies in Evaluating Cardiovascular Therapies. Circulation
118: 1294-1303
[Full Text]
Beyer, A. M., de Lange, W. J., Halabi, C. M., Modrick, M. L., Keen, H. L., Faraci, F. M., Sigmund, C. D.
(2008). Endothelium-Specific Interference With Peroxisome Proliferator Activated Receptor Gamma Causes Cerebral Vascular Dysfunction in Response to a High-Fat Diet. Circ. Res.
103: 654-661
[Abstract][Full Text]
Goldfine, A. B.
(2008). Assessing the Cardiovascular Safety of Diabetes Therapies. NEJM
359: 1092-1095
[Full Text]
(PPAR-
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