Advanced Search

Completed Systematic Reviews




Oral Diabetes Medications for Adults With Type 2 Diabetes: An Update [Entered Retrospectively]


Public Project Complete

Statistics: 176 Studies, 4 Key Questions, 4 Extraction Forms,
Date Published: Jul 23, 2015 02:36PM
Description: Objectives: Given the number of medications available for type 2 diabetes mellitus, clinicians and patients need information about their effectiveness and safety to make informed choices. The objective of this review was to summarize the benefits and harms of medications (metformin, second-generation sulfonylureas, thiazolidinediones, meglitinides, dipeptidyl peptidase-4 [DPP- 4] inhibitors, and glucagon-like peptide-1 [GLP-1] receptor agonists), as monotherapy and in combination, for the treatment of adults with type 2 diabetes; Data Sources: We searched the MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases from inception through April 2010 for original English-language articles and sought unpublished data from the Food and Drug Administration and others; Review Methods: Two reviewers independently screened titles to identify studies that assessed intermediate outcomes (e.g., hemoglobin A1c [HbA1c]), long-term clinical outcomes (e.g., mortality), and harms (e.g., hypoglycemia) in head-to-head monotherapy or combination therapy comparisons. Two reviewers serially extracted data for each article using standardized protocols, assessed applicability, and independently evaluated study quality; Results: The review included 140 randomized controlled trials and 26 observational studies. We graded evidence as low or insufficient for long-term clinical outcomes of all-cause mortality, cardiovascular disease, nephropathy, and neuropathy. Most medications lowered HbA1c on average by 1 absolute percentage point, but metformin was more efficacious than the DPP-4 inhibitors. Two-drug combinations had similar HbA1c reduction. Compared with metformin, thiazolidinediones and sulfonylureas had a more unfavorable effect on weight (mean difference of +2.6 kg). Metformin decreased low density lipoprotein cholesterol relative to pioglitazone, sulfonylureas, and DPP-4 inhibitors. Sulfonylureas had a fourfold higher risk of mild/moderate hypoglycemia compared with metformin alone, and, in combination with metformin, had more than a fivefold increased risk compared with metformin plus thiazolidinediones. Thiazolidinediones had an increased risk of congestive heart failure relative to sulfonylureas and bone fractures relative to metformin. Diarrhea occurred more often for metformin compared with thiazolidinedione users; Conclusions: Comprehensive information comparing benefits and harms of diabetes medications can facilitate personalized treatment choices for patients. Although the long-term benefits and harms of diabetes medications remain unclear, the evidence supports use of metformin as a first- line agent. Comparisons of two-drug combinations showed little to no difference in HbA1c reduction, but some combinations increased risk for hypoglycemia and other adverse events.
Contributor(s): Wendy L. Bennett, MD, MPH; Lisa M. Wilson, ScM; Shari Bolen, MD, MPH; Nisa Maruthur, MD; Sonal Singh, MD; Ranee Chatterjee, MD, MPH; Spyridon S. Marinopoulos, MD, MBA; Milo A. Puhan, MD, PhD; Padmini Ranasinghe, MD, MPH; Wanda K. Nicholson, MD, MPH; Lauren Block, MD; Olaide Odelola, MBBS, MPH; Deepan S. Dalal, MBBS, MPH; Grace E. Ogbeche, MBBS, MPH; Aditya Chandrasekhar, MBBS; Susan Hutfless, PhD; Eric B. Bass, MD, MPH; Jodi B. Segal, MD, MPH
Funding Source: The Agency for Healthcare Research and Quality (AHRQ)
Methodology Description: We searched the following databases for primary studies for the periods in parentheses: MEDLINE® (1966 to April 2010), Embase® (1974 to April 2010), and the Cochrane Central Register of Controlled Trials (1966 to April 2010). We updated the MEDLINE search to December 2010 for long-term clinical outcomes (i.e., all-cause mortality, cardiovascular morbidity and mortality, nephropathy and neuropathy). We developed a search strategy for MEDLINE, accessed via PubMed, based on an analysis of the medical subject headings (MeSH) terms and text words of key articles identified a priori. Our search strategy was similar to the one used for the initial 2007 review,21 but it included terms for the additional medications included in this review (Appendix B). In addition, we received the following material from the Scientific Resource Center: • Medical reviews of rosiglitazone, pioglitazone, sitagliptin, glyburide, and metformin, combination of metformin and glipizide, combination of metformin and sitagliptin, insulin detemir, exenatide and postmarketing drug safety information on pioglitazone and insulin glargine from the FDA Web site • The Scientific Discussion sections of the European Public Assessment Reports for rosiglitazone, pioglitazone, sitagliptin, combination rosiglitazone and metformin, exenatide, insulin detemir, and insulin glargine • Health Canada Product Monographs for rosiglitazone, pioglitazone, sitagliptin, combination rosiglitazone and metformin, insulin glargine, and insulin detemir • Public registries of clinical trials, such as Clinical Study Results Web site (available at: www.clinicalstudyresults.org) and ClinicalTrials.gov (available at: www.clinicaltrials.gov). We hand searched 15 journals that most likely to publish articles on this topic (see Appendix C) by scanning the table of contents of each issue for relevant citations from February 2009 through September 2009. We also reviewed the reference lists of each included article and relevant review articles. The results of the searches were downloaded and imported into ProCite® version 5 (ISI ResearchSoft, Carlsbad, CA). We scanned for exact article duplicates, author/title duplicates, and title duplicates using the duplication check feature in ProCite.® From ProCite, the articles were uploaded to DistillerSR (Evidence Partners, Ottawa, Ontario, Canada), a Web-based software package developed for systematic review data management. This database was used to track the search results at the levels of title review, abstract review, article inclusion/exclusion, and data abstraction.

Zoom Preview | Show Downloadable Content

Low-calorie sweeteners and body weight and composition: a meta-analysis of randomized controlled trials and prospective cohort studies


Public Project Complete

Statistics: 24 Studies, 2 Key Questions, 2 Extraction Forms,
Date Published: Jul 23, 2015 02:34PM
Description: The objective of this project is to systematically review and quantitatively evaluate randomized controlled trials and prospective cohort studies, separately, that examined the relationship between low-calorie sweeteners and body weight and composition.
Contributor(s): None Provided
Funding Source: Supported by funding from the North American Branch of the International Life Sciences Institute.
Methodology Description: A systematic literature search identified 15 randomized controlled trials and 9 prospective cohort studies that examined low-calorie sweeteners from foods or beverages, or low-calorie sweeteners consumed as tabletop sweeteners. Meta-analyses generated weighted mean differences in body weight and composition values between the low-calorie sweetener and control groups among randomized controlled trials, and weighted mean correlations for low-calorie sweetener intake and these parameters among prospective cohort studies.

Zoom Preview | Show Downloadable Content

Interventions to Reduce Antibiotic Prescribing for Uncomplicated Acute Respiratory Tract Infections [Entered Retrospectively]


Public Project Complete

Statistics: 133 Studies, 6 Key Questions, 1 Extraction Form,
Date Published: Jul 23, 2015 02:34PM
Description: Objectives. To assess the comparative effectiveness of interventions for reducing antibiotic use for acute respiratory tract infections (RTIs) in adults and children. Data Sources. Electronic databases (MEDLINE® from 1990 and the Cochrane Library databases from 2005 to February 2015), reference lists of included systematic reviews, and scientific information packets from of point-of-care test manufacturers and experts. Review Methods. Using predefined criteria, we selected studies of any intervention designed to reduce antibiotic prescribing for acute RTIs. Interventions were organized into educational, communication, clinical, system level, and multifaceted categories. The key outcome was change in prescribing; secondary outcomes were undesirable consequences such as medical complications and satisfaction. The quality of included studies was rated and the strength of the evidence was assessed. Clinical and methodological heterogeneity limited quantitative analysis. Our synthesis focused on interventions that had evidence of net benefit: at least moderate strength of evidence for decreasing overall prescribing of antibiotics for acute RTI and at least low strength evidence for other outcomes. Results. Based on 132 studies, including 88 randomized controlled trials, several interventions had net benefit. Compared with usual care, reductions in overall prescribing were 21 percent for clinic-based educational programs for parents, 7 percent for public education campaigns combined with clinician education, 9 to 26 percent for communication training, 5 to 9 percent for electronic decision support, 2 to 34 percent for C-reactive protein (CRP), 12 to 72 percent for procalcitonin in adults, and >25 percent for clinician communication training plus CRP testing. Delayed prescribing reduced use by 34 to 76 percent compared with immediate prescribing. Additionally, public education campaigns combined with clinician education and electronic decision support possibly improved appropriate prescribing. Interventions varied in their effects on other outcomes. Few studies assessed impact on the most serious undesirable outcomes, but in those that did, there were no increases in medical complications for public education campaigns combined with clinician education or electronic decision support and, for hospitalizations, no increases for CRP or procalcitonin and only a slight increase for communication+CRP. Negative impacts on less serious outcomes were few and small: more return visits with CRP testing, slightly longer symptom duration with communication training plus CRP testing, and decreased patient satisfaction and slightly longer symptom duration with delayed prescribing. Direct comparisons of interventions were few; only clinician communication training plus CRP testing showed net benefit over CRP testing alone. Interventions with no or negative impact on antibiotic prescribing were procalcitonin in children, clinic-based education for parents of children ≤24 months with acute otitis media, and point-of-care testing for influenza in children. Conclusions. Interventions from all categories had evidence of net benefit and no serious adverse consequences. Magnitude of benefit varied widely and current evidence is inadequate to determine key modifying factors. Future studies need to better evaluate potential effect modifiers, and directly compare the effective interventions individually and combined, on net benefit, sustainability, and resource use.
Contributor(s): Marian McDonagh, Pharm.D., Kim Peterson, M.S., Kevin Winthrop, M.D., M.P.H., Amy Cantor, M.D., Brittany Holzhammer, M.P.H., David Buckley, M.D., M.P.H.
Funding Source: This report is based on research conducted by the Pacific Northwest Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. HHSA290201200014I).
Methodology Description: Using predefined criteria, we selected studies of any intervention designed to reduce antibiotic prescribing for acute RTIs. Interventions were organized into educational, communication, clinical, system level, and multifaceted categories. The key outcome was change in prescribing; secondary outcomes were undesirable consequences such as medical complications and satisfaction. The quality of included studies was rated and the strength of the evidence was assessed. Clinical and methodological heterogeneity limited quantitative analysis. Our synthesis focused on interventions that had evidence of net benefit: at least moderate strength of evidence for decreasing overall prescribing of antibiotics for acute RTI and at least low strength evidence for other outcomes.

Zoom Preview | Show Downloadable Content

Imaging Tests for the Diagnosis and Staging of Pancreatic Adenocarcinoma


Public Project Complete

Statistics: 121 Studies, 6 Key Questions, 5 Extraction Forms,
Date Published: Jul 23, 2015 02:33PM
Description: Systematic review of imaging tests for diagnosis, staging, and/or screening of pancreatic adenocarcinoma
Contributor(s): Jonathan Treadwell, Ph.D., Matthew Mitchell, Ph.D., Kelley Eatmon, M.P.H., Jane Jue, M.D., M.Sc., Hanna Zafar, M.D., M.H.S., Ursina Teitelbaum, M.D., Karen Schoelles, M.D., S.M., F.A.C.P.
Funding Source: AHRQ
Methodology Description: EPC report

Zoom Preview | Show Downloadable Content

Fructose Consumption and Non-alcoholic Fatty Liver Disease (NAFLD)


Public Project Complete

Statistics: 23 Studies, 5 Key Questions, 4 Extraction Forms,
Date Published: Jul 23, 2015 02:30PM
Description: Background: There are growing concerns about the effects of dietary fructose on health outcomes because the intakes appear to have parallel trends in non-alcoholic fatty liver disease (NAFLD) and obesity prevalence in the United States. Purpose: To examine the effect of different levels and sources of dietary fructose on the incidence or prevalence of NAFLD and on indices of liver health in humans. Data Sources: English-language studies identified from MEDLINE, Cochrane Central Register of Controlled Trials, CAB Abstracts, and Global Health databases up to September 2012. Study Selection: Human studies of any design in children and adults with low to no alcohol intake and reporting at least one predetermined measure of liver health. Data Extraction: Study data was extracted by one investigator and corroborated by a second investigator. Differences were resolved by consensus. Data Synthesis: Twenty-two studies met the inclusion criteria, 3 reported NAFLD outcomes and 19 reported indices of liver health. Of these, all but 1 study were rated at medium or high risk of bias. The overall strength of evidence for an association between fructose intake and incidence of NAFLD was rated insufficient because of the biases and confounding in the study results. The 19 studies reporting indices of liver health were synthesized separately by each outcome: liver fat outcomes (7 studies), liver enzymes (11 studies), hepatic de novo lipogenesis rates (2 studies), and plasma bilirubin concentrations (2 studies). The overall strength of evidence was rated insufficient for all outcomes, except for some plasma liver enzymes. Our random-effects meta-analysis of 3 short-term RCTs (6 to 7 days) showed a significant increase in alanine aminotransferase (ALT) concentrations (+4.32 IU/L, 95% CI 0.20, 8.43, P=0.04) when a free fructose enriched excess energy diet was compared to a habitual weight maintenance diet. Limitations: Most studies were rated at medium or high risk of bias, were small in sample size, included healthy adult men only, and were highly heterogeneous in study design and intervention, and thus limiting comparability. Conclusions: Due to scarce, poor-quality, and heterogeneous data, we concluded that evidence is insufficient to draw conclusions regarding the effect of fructose consumption on NAFLD, while there is low level of evidence for a relationship between high free fructose intake in excess of energy needs and elevated liver enzyme concentrations. Large prospective cohort studies using standard NAFLD diagnosis are needed to examine the complex relationships between dietary factors and the risk of NAFLD.
Contributor(s): Mei Chung, PhD, MPH Jiantao Ma, MD, MS Kamal Patel, MPH, MBA Samantha Berger, BS Joseph Lau, MD Alice H. Lichtenstein, ScD
Funding Source: The International Life Sciences Institute (ILSI) North American Branch
Methodology Description: See Chung M, Ma J, Patel K, Berger S, Lau J, Lichtenstein AH. Fructose, high-fructose corn syrup, sucrose, and nonalcoholic fatty liver disease or indexes of liver health: a systematic review and meta-analysis. Am J Clin Nutr. 2014 Sep;100(3):833-49. doi: 10.3945/ajcn.114.086314. Epub 2014 Aug 6. PubMed PMID: 25099546; PubMed Central PMCID: PMC4135494.

Zoom Preview | Show Downloadable Content