Search

Introduction Type 2 diabetes mellitus (T2DM) is a powerful risk factor for cardiovascular disease (CVD), conferring a greater relative risk in women than men. We sought to examine sex differences in cardiometabolic risk factors and management in the contemporary cohort represented by the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE).Research design and methods GRADE enrolled 5047 participants (1837 women, 3210 men) with T2DM on metformin monotherapy at baseline. The current report is a cross-sectional analysis of baseline data collected July 2013 to August 2017.Results Compared with men, women had a higher mean body mass index (BMI), greater prevalence of severe obesity (BMI≥40 kg/m2), higher mean LDL cholesterol, greater prevalence of low HDL cholesterol, and were less likely to receive statin treatment and achieve target LDL, with a generally greater prevalence of these risk factors in younger women. Women with hypertension were equally likely to achieve blood pressure targets as men; however, women were less likely to receive ACE inhibitors or angiotensin receptor blockers. Women were more likely to be divorced, separated or widowed, and had fewer years of education and lower incomes.Conclusions This contemporary cohort demonstrates that women with T2DM continue to have a greater burden of cardiometabolic and socioeconomic risk factors than men, particularly younger women. Attention to these persisting disparities is needed to reduce the burden of CVD in women.Trial registration number ClinicalTrials.gov (NCT01794143)

Objective: Hypoglycemia is a major concern in type 2 diabetes (T2DM), but little is known about its likelihood compared across common therapies. We compared the likelihood of hypoglycemia among metformin-treated patients with T2DM randomized to the addition of one of 4 common therapies., Research Design & Methods: Randomized, controlled trial of 5,047 participants with T2DM of <10 years' duration, hemoglobin A1c (HbA1c) 6.8-8.5% (50.8-69.4 mmol/mol). Randomization to addition of glargine U100, glimepiride, liraglutide, or sitagliptin over 5.0 ± 1.3 (mean ± SD) years. HbA1c was measured quarterly; if a level >7.5% (>58.5 mmol/mol) was confirmed, rescue glargine and/or aspart insulin was added. We conducted a per-protocol analysis of 4,830, who attended at least one post-baseline visit and took at least one dose of assigned study medication. We assessed severe hypoglycemia events reported throughout the entire study. At quarterly visits, all participants were asked about hypoglycemic symptoms within the last 30 days, and those in the glargine and glimepiride groups were asked for any measured glucose <70 mg/dL (3.9 mmol/L) within this time period., Results: While participants were taking their assigned medications, severe hypoglycemia occurred in 10 (0.8%), 16 (1.3%), 6 (0.5%), and 4 (0.3%), (p<0.05) and hypoglycemic symptoms in 659 (54.2%), 833 (68.3%), 375 (32.4%), and 361 (29.1%) of participants following randomization to glargine, glimepiride, liraglutide, and sitagliptin, respectively (p<0.001)., Conclusions: In metformin-treated patients with T2DM who add a second medication, hypoglycemia is most likely with addition of glimepiride, less with glargine, and least likely with liraglutide and sitagliptin., Trial Registration: ClinicalTrials.gov Identifier: NCT01794143., Competing Interests: Outside the submitted work, Dr. Elizabeth Seaquist reports grants or contracts from JDRF to her institution; consulting fees from Lily, NovoNordisk, Sanofi, and Zucara; honoraria from International Hypoglycemia study group; board membership with the American Diabetes Association; and receipt of sensors from Dexcom to her institution. Dr. Lawrence Phillips reports salary support from the Veterans Health Administration during the conduct of the study; grants from Janssen Pharmaceuticals, grants from Merck, Amylin, Eli Lilly, Novo Nordisk, Sanofi, PhaseBio, Roche, AbbVie, Vascular Pharmaceuticals, GlaxoSmithKline, Pfizer, AstraZeneca, Kowa, and Cystic Fibrosis Foundation; other support from DIASYST, outside the submitted work. Outside the submitted work, Dr. Richard M. Bergenstal reports consulting fees from Abbot Diabetes Care, Ascencia, Bigfoot Biomedical, Inc., DexCom, MannKind, Medtronic, Novo Nordisk, Sanofi, and United Health Care made to HealthPartners Institute; payments or honoraria from Sanofi and Vertex Pharmaceuticals made to Health Partners Institute; support for meetings or travel from Abbott Diabetes Care, Ascensia, CeQur, Eli Lilly, Embecta, MannKind, Novo Nordisk, Roche GmbH, Sanofi, Vertex Pharmaceuticals, and Zealand Pharma made to Health Partners Institute, and participation on a data safety monitoring or advisory board from Abbott Diabetes Care, CeQur, Eli Lilly, Embecta, Hygieia, Roche GmbH, and Zealand Pharma with payments made to HealthPartners Institute. Outside the submitted work, Dr. Jill Crandall reports non-financial support from Abbott. Outside the submitted work, Mary L Johnson reports research grants paid to Health Partners Institute from Sanofi, Novo Nordisk, and Lilly. Dr. Alokananda Ghosh, Dr. Naji Younes, Dr. John Lachin, Chelsea Baker, Dr. Robin S. Goland, Michaela R Gramzinski, Dr. Daniel S Hsia, Dr. Sophia H Hox, Dr. Philip Raskin, Dr. Willy M Valencia, and Andrea H Waltje have nothing to disclose. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background/aims: We present and describe recruitment strategies implemented from 2013 to 2017 across 45 clinical sites in the United States, participating in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study, an unmasked, randomized controlled trial evaluating four glucose-lowering medications added to metformin in individuals with type 2 diabetes mellitus (duration of diabetes <10 years). We examined the yield of participants recruited through Electronic Health Records systems compared to traditional recruitment methods to leverage access to type 2 diabetes patients in primary care., Methods: Site selection criteria included availability of the study population, geographic representation, the ability to recruit and retain a diverse pool of participants including traditionally underrepresented groups, and prior site research experience in diabetes clinical trials. Recruitment initiatives were employed to support and monitor recruitment, such as creation of a Recruitment and Retention Committee, development of criteria for Electronic Health Record systems queries, conduct of remote site visits, development of a public screening website, and other central and local initiatives. Notably, the study supported a dedicated recruitment coordinator at each site to manage local recruitment and facilitate screening of potential participants identified by Electronic Health Record systems., Results: The study achieved the enrollment goal of 5000 participants, meeting its target with Black/African American (20%), Hispanic/Latino (18%), and age ≧60 years (42%) subgroups but not with women (36%). Recruitment required 1 year more than the 3 years originally planned. Sites included academic hospitals, integrated health systems, and Veterans Affairs Medical Centers. Participants were enrolled through Electronic Health Record queries (68%), physician referral (13%), traditional mail outreach (7%), TV, radio, flyers, and Internet (7%), and other strategies (5%). Early implementation of targeted Electronic Health Record queries yielded a greater number of eligible participants compared to other recruitment methods. Efforts over time increasingly emphasized engagement with primary care networks., Conclusion: Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness successfully recruited a diverse study population with relatively new onset of type 2 diabetes mellitus, relying to a large extent on the use of Electronic Health Record to screen potential participants. A comprehensive approach to recruitment with frequent monitoring was critical to meet the recruitment goal.

Aims: We evaluated differences in participants with type 2 diabetes (T2DM) enrolled in the GRADE study at VA vs non-VA sites, focusing on cardiovascular risk factors and rates of diabetes care target achievements., Methods: We compared baseline characteristics between participants at VA (n = 1216) and non-VA (n = 3831) sites, stratifying analyses by cardiovascular disease (CVD) history., Results: VA and non-VA participants had similar diabetes duration (4.0 years), HbA1c (7.5%), and BMI (34 kg/m 2 ); however, VA participants had more individuals ≥ 65 years (37.3% vs 19.8%, p < 0.001), men (90.0% vs 55.2%, p < 0.001), hypertension (75.8% vs 63.6%, p < 0.001), hyperlipidemia (76.6% vs 64.6%, p < 0.001), current smokers (19.0% vs 12.1%, p < 0.001), nephropathy (20.4% vs 17.0%, p < 0.05), albuminuria (18.4% vs 15.1%, p < 0.05), and CVD (10.4% vs 5.2%, p < 0.001). In those without CVD, more VA participants were treated with lipid (70.8% vs 59.5%, p < 0.001) and blood pressure (74.9% vs 65.4%, p < 0.001) lowering medications, and had LDL-C < 70 mg/dl (32.9% vs 24.2%, p < 0.05). Among those with CVD, more VA participants had BP < 140/90 (80.2% vs 70.1%, p < 0.05) after adjusting for demographics., Conclusion: GRADE participants at VA sites had more T2DM complications, greater CVD risk and were more likely to be treated with medications to reduce it, leading to more LDL-C at goal than non-VA participants, highlighting differences in diabetes populations and care., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: GRADE (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study) is a 36-center unmasked, parallel treatment group, randomized controlled trial evaluating four diabetes medications added to metformin in people with type 2 diabetes (T2DM). We report baseline characteristics and compare GRADE participants to a National Health and Nutrition Examination Survey (NHANES) cohort., Research Design and Methods: Participants were age ≥30 years at the time of diagnosis, with duration of T2DM <10 years, HbA 1c 6.8-8.5% (51-69 mmol/mol), prescribed metformin monotherapy, and randomized to glimepiride, sitagliptin, liraglutide, or insulin glargine., Results: At baseline, GRADE's 5,047 randomized participants were 57.2 ± 10.0 years of age, 63.6% male, with racial/ethnic breakdown of 65.7% white, 19.8% African American, 3.6% Asian, 2.7% Native American, 7.6% other or unknown, and 18.4% Hispanic/Latino. Duration of diabetes was 4.2 ± 2.8 years, with mean HbA 1c of 7.5 ± 0.5% (58 ± 5.3 mmol/mol), BMI of 34.3 ± 6.8 kg/m 2 , and metformin dose of 1,944 ± 204 mg/day. Among the cohort, 67% reported a history of hypertension, 72% a history of hyperlipidemia, and 6.5% a history of heart attack or stroke. Applying GRADE inclusion criteria to NHANES indicates enrollment of a representative cohort with T2DM on metformin monotherapy (NHANES cohort average age, 57.9 years; mean HbA 1c , 7.4% [57 mmol/mol]; BMI, 33.2 kg/m 2 ; duration, 4.2 ± 2.5 years; and 7.2% with a history of cardiovascular disease)., Conclusions: The GRADE cohort represents patients with T2DM treated with metformin requiring a second diabetes medication. GRADE will inform decisions about the clinical effectiveness of the addition of four classes of diabetes medications to metformin., (© 2019 by the American Diabetes Association.)