Treatment of Type 2 Diabetes and Outcomes in Patients With Heart Failure: A Nested Case-Control Study From the U.K. General Practice Research Database
OBJECTIVE: Diabetes and heart failure commonly coexist, and prior studies have suggested better outcomes with metformin than other antidiabetic agents. We designed this study to determine whether this association reflects a beneficial effect of metformin or a harmful effect of other agents. RESEARCH...
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| Published in | Diabetes care Vol. 33; no. 6; pp. 1213 - 1218 |
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| Main Authors | , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Alexandria, VA
American Diabetes Association
01.06.2010
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| Subjects | |
| Online Access | Get full text |
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| Abstract | OBJECTIVE: Diabetes and heart failure commonly coexist, and prior studies have suggested better outcomes with metformin than other antidiabetic agents. We designed this study to determine whether this association reflects a beneficial effect of metformin or a harmful effect of other agents. RESEARCH DESIGN AND METHODS: We performed a case-control study nested within the U.K. General Practice Research Database cohort in which diagnoses were assigned by each patient's primary care physician. Case subjects were patients 35 years or older, newly diagnosed with both heart failure and diabetes after January 1988, and who died prior to October 2007. Control subjects were matched to case subjects based on age, sex, clinic site, calendar year, and duration of follow-up. Analyses were adjusted for comorbidities, A1C, renal function, and BMI. RESULTS: The duration of concurrent diabetes and heart failure was 2.8 years (SD 2.6) in our 1,633 case subjects and 1,633 control subjects (mean age 78 years, 53% male). Compared with patients who were not exposed to antidiabetic drugs, the current use of metformin monotherapy (adjusted odds ratio 0.65 [0.48-0.87]) or metformin with or without other agents (0.72 [0.59-0.90]) was associated with lower mortality; however, use of other antidiabetic drugs or insulin was not associated with all-cause mortality. Conversely, the use of ACE inhibitors/angiotensin receptor blockers (0.55 [0.45-0.68]) and β-blockers (0.76 [0.61-0.95]) were associated with reduced mortality. CONCLUSIONS: Our results confirm the benefits of trial-proven anti-failure therapies in patients with diabetes and support the use of metformin-based strategies to lower glucose. |
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| AbstractList | Diabetes and heart failure commonly coexist, and prior studies have suggested better outcomes with metformin than other antidiabetic agents. We designed this study to determine whether this association reflects a beneficial effect of metformin or a harmful effect of other agents.
We performed a case-control study nested within the U.K. General Practice Research Database cohort in which diagnoses were assigned by each patient's primary care physician. Case subjects were patients 35 years or older, newly diagnosed with both heart failure and diabetes after January 1988, and who died prior to October 2007. Control subjects were matched to case subjects based on age, sex, clinic site, calendar year, and duration of follow-up. Analyses were adjusted for comorbidities, A1C, renal function, and BMI.
The duration of concurrent diabetes and heart failure was 2.8 years (SD 2.6) in our 1,633 case subjects and 1,633 control subjects (mean age 78 years, 53% male). Compared with patients who were not exposed to antidiabetic drugs, the current use of metformin monotherapy (adjusted odds ratio 0.65 [0.48-0.87]) or metformin with or without other agents (0.72 [0.59-0.90]) was associated with lower mortality; however, use of other antidiabetic drugs or insulin was not associated with all-cause mortality. Conversely, the use of ACE inhibitors/angiotensin receptor blockers (0.55 [0.45-0.68]) and beta-blockers (0.76 [0.61-0.95]) were associated with reduced mortality.
Our results confirm the benefits of trial-proven anti-failure therapies in patients with diabetes and support the use of metformin-based strategies to lower glucose. Diabetes and heart failure commonly coexist, and prior studies have suggested better outcomes with metformin than other antidiabetic agents. We designed this study to determine whether this association reflects a beneficial effect of metformin or a harmful effect of other agents. We performed a case-control study nested within the U.K. General Practice Research Database cohort in which diagnoses were assigned by each patient's primary care physician. Case subjects were patients 35 years or older, newly diagnosed with both heart failure and diabetes after January 1988, and who died prior to October 2007. Control subjects were matched to case subjects based on age, sex, clinic site, calendar year, and duration of follow-up. Analyses were adjusted for comorbidities, A1C, renal function, and BMI. The duration of concurrent diabetes and heart failure was 2.8 years (SD 2.6) in our 1,633 case subjects and 1,633 control subjects (mean age 78 years, 53% male). Compared with patients who were not exposed to antidiabetic drugs, the current use of metformin monotherapy (adjusted odds ratio 0.65 [0.48-0.87]) or metformin with or without other agents (0.72 [0.59-0.90]) was associated with lower mortality; however, use of other antidiabetic drugs or insulin was not associated with all-cause mortality. Conversely, the use of ACE inhibitors/angiotensin receptor blockers (0.55 [0.45-0.68]) and β-blockers (0.76 [0.61-0.95]) were associated with reduced mortality. Our results confirm the benefits of trial-proven anti-failure therapies in patients with diabetes and support the use of metformin-based strategies to lower glucose. OBJECTIVE: Diabetes and heart failure commonly coexist, and prior studies have suggested better outcomes with metformin than other antidiabetic agents. We designed this study to determine whether this association reflects a beneficial effect of metformin or a harmful effect of other agents. RESEARCH DESIGN AND METHODS: We performed a case-control study nested within the U.K. General Practice Research Database cohort in which diagnoses were assigned by each patient's primary care physician. Case subjects were patients 35 years or older, newly diagnosed with both heart failure and diabetes after January 1988, and who died prior to October 2007. Control subjects were matched to case subjects based on age, sex, clinic site, calendar year, and duration of follow-up. Analyses were adjusted for comorbidities, A1C, renal function, and BMI. RESULTS: The duration of concurrent diabetes and heart failure was 2.8 years (SD 2.6) in our 1,633 case subjects and 1,633 control subjects (mean age 78 years, 53% male). Compared with patients who were not exposed to antidiabetic drugs, the current use of metformin monotherapy (adjusted odds ratio 0.65 [0.48-0.87]) or metformin with or without other agents (0.72 [0.59-0.90]) was associated with lower mortality; however, use of other antidiabetic drugs or insulin was not associated with all-cause mortality. Conversely, the use of ACE inhibitors/angiotensin receptor blockers (0.55 [0.45-0.68]) and β-blockers (0.76 [0.61-0.95]) were associated with reduced mortality. CONCLUSIONS: Our results confirm the benefits of trial-proven anti-failure therapies in patients with diabetes and support the use of metformin-based strategies to lower glucose. Diabetes and heart failure commonly coexist, and prior studies have suggested better outcomes with metformin than other antidiabetic agents. We designed this study to determine whether this association reflects a beneficial effect of metformin or a harmful effect of other agents.OBJECTIVEDiabetes and heart failure commonly coexist, and prior studies have suggested better outcomes with metformin than other antidiabetic agents. We designed this study to determine whether this association reflects a beneficial effect of metformin or a harmful effect of other agents.We performed a case-control study nested within the U.K. General Practice Research Database cohort in which diagnoses were assigned by each patient's primary care physician. Case subjects were patients 35 years or older, newly diagnosed with both heart failure and diabetes after January 1988, and who died prior to October 2007. Control subjects were matched to case subjects based on age, sex, clinic site, calendar year, and duration of follow-up. Analyses were adjusted for comorbidities, A1C, renal function, and BMI.RESEARCH DESIGN AND METHODSWe performed a case-control study nested within the U.K. General Practice Research Database cohort in which diagnoses were assigned by each patient's primary care physician. Case subjects were patients 35 years or older, newly diagnosed with both heart failure and diabetes after January 1988, and who died prior to October 2007. Control subjects were matched to case subjects based on age, sex, clinic site, calendar year, and duration of follow-up. Analyses were adjusted for comorbidities, A1C, renal function, and BMI.The duration of concurrent diabetes and heart failure was 2.8 years (SD 2.6) in our 1,633 case subjects and 1,633 control subjects (mean age 78 years, 53% male). Compared with patients who were not exposed to antidiabetic drugs, the current use of metformin monotherapy (adjusted odds ratio 0.65 [0.48-0.87]) or metformin with or without other agents (0.72 [0.59-0.90]) was associated with lower mortality; however, use of other antidiabetic drugs or insulin was not associated with all-cause mortality. Conversely, the use of ACE inhibitors/angiotensin receptor blockers (0.55 [0.45-0.68]) and beta-blockers (0.76 [0.61-0.95]) were associated with reduced mortality.RESULTSThe duration of concurrent diabetes and heart failure was 2.8 years (SD 2.6) in our 1,633 case subjects and 1,633 control subjects (mean age 78 years, 53% male). Compared with patients who were not exposed to antidiabetic drugs, the current use of metformin monotherapy (adjusted odds ratio 0.65 [0.48-0.87]) or metformin with or without other agents (0.72 [0.59-0.90]) was associated with lower mortality; however, use of other antidiabetic drugs or insulin was not associated with all-cause mortality. Conversely, the use of ACE inhibitors/angiotensin receptor blockers (0.55 [0.45-0.68]) and beta-blockers (0.76 [0.61-0.95]) were associated with reduced mortality.Our results confirm the benefits of trial-proven anti-failure therapies in patients with diabetes and support the use of metformin-based strategies to lower glucose.CONCLUSIONSOur results confirm the benefits of trial-proven anti-failure therapies in patients with diabetes and support the use of metformin-based strategies to lower glucose. |
| Audience | Professional |
| Author | McAlister, Finlay A Petrie, Mark C Eurich, Dean T Petrie, John R MacDonald, Michael R Bhagra, Sai Jhund, Pardeep S Majumdar, Sumit R McMurray, John J.V Lewsey, James D |
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| Keywords | Endocrinopathy Type 2 diabetes Human Heart failure Prognosis Nutrition Cardiovascular disease Patient Metabolic diseases Case control study Epidemiology Treatment Heart disease Scientific research Database Evolution General practice Endocrinology Public health |
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| PublicationTitle | Diabetes care |
| PublicationTitleAlternate | Diabetes Care |
| PublicationYear | 2010 |
| Publisher | American Diabetes Association |
| Publisher_xml | – name: American Diabetes Association |
| References | Dargie (2022031218230567800_B2) 2007; 49 Maru (2022031218230567800_B7) 2005; 28 Witteles (2022031218230567800_B13) 2008; 51 Montori (2022031218230567800_B17) 2009; 150 Hippisley-Cox (2022031218230567800_B8) 2004; 364 McAlister (2022031218230567800_B20) 2003; 138 Masoudi (2022031218230567800_B1) 2007; 99 Selvin (2022031218230567800_B22) 2008; 168 Eurich (2022031218230567800_B3) 2007; 335 Suskin (2022031218230567800_B11) 2000; 21 Shah (2022031218230567800_B4) 2010; 16 Aguilar (2022031218230567800_B16) 2009; 54 Bolen (2022031218230567800_B21) 2007; 147 Essebag (2022031218230567800_B6) 2005; 5 Eshaghian (2022031218230567800_B15) 2006; 151 Gerstein (2022031218230567800_B14) 2008; 168 Tzoulaki (2022031218230567800_B9) 2009; 339 Saccà (2022031218230567800_B12) 2009; 19 Haas (2022031218230567800_B19) 2003; 146 Doehner (2022031218230567800_B10) 2005; 46 Gelfand (2022031218230567800_B5) 2005 Shekelle (2022031218230567800_B18) 2003; 41 |
| References_xml | – volume: 364 start-page: 423 year: 2004 ident: 2022031218230567800_B8 article-title: Prevalence, care, and outcomes for patients with diet-controlled diabetes in general practice: cross sectional survey publication-title: Lancet doi: 10.1016/S0140-6736(04)16765-2 – volume: 5 start-page: 5 year: 2005 ident: 2022031218230567800_B6 article-title: Comparison of nested case-control and survival analysis methodologies for analysis of time-dependent exposure publication-title: BMC Med Res Methodol doi: 10.1186/1471-2288-5-5 – volume: 168 start-page: 2070 issue: 19 year: 2008 ident: 2022031218230567800_B22 article-title: Cardiovascular outcomes in trials of oral diabetes medications: a systematic review publication-title: Arch Intern Med doi: 10.1001/archinte.168.19.2070 – volume: 150 start-page: 803 year: 2009 ident: 2022031218230567800_B17 article-title: Glycemic control in type 2 diabetes: time for an evidence-based about-face? publication-title: Ann Intern Med doi: 10.7326/0003-4819-150-11-200906020-00008 – volume: 168 start-page: 1699 year: 2008 ident: 2022031218230567800_B14 article-title: The hemoglobin A1C level as a progressive risk factor for cardiovascular death, hospitalization for heart failure, or death in patients with chronic heart failure: an analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and Morbidity (CHARM) program publication-title: Arch Intern Med doi: 10.1001/archinte.168.15.1699 – volume: 99 start-page: 113B year: 2007 ident: 2022031218230567800_B1 article-title: Diabetes mellitus and heart failure: epidemiology, mechanisms, and pharmacotherapy publication-title: Am J Cardiol doi: 10.1016/j.amjcard.2006.11.013 – volume: 28 start-page: 20 year: 2005 ident: 2022031218230567800_B7 article-title: Antidiabetic drugs and heart failure risk in patients with type 2 diabetes in the U.K. primary care setting publication-title: Diabetes Care doi: 10.2337/diacare.28.1.20 – volume: 151 start-page: 91 year: 2006 ident: 2022031218230567800_B15 article-title: An unexpected inverse relationship between HbA1C levels and mortality in patients with diabetes and advanced systolic heart failure publication-title: Am Heart J doi: 10.1016/j.ahj.2005.10.008 – volume: 335 start-page: 497 year: 2007 ident: 2022031218230567800_B3 article-title: Benefits and harms of antidiabetic agents in patients with diabetes and heart failure: systematic review publication-title: BMJ doi: 10.1136/bmj.39314.620174.80 – volume: 16 start-page: 200 year: 2010 ident: 2022031218230567800_B4 article-title: Metformin therapy and outcomes in patients with advanced systolic heart failure and diabetes publication-title: J Card Fail doi: 10.1016/j.cardfail.2009.10.022 – volume: 19 start-page: 303 year: 2009 ident: 2022031218230567800_B12 article-title: Insulin resistance in chronic heart failure: a difficult bull to take by the horns publication-title: Nutr Metab Cardiovasc Dis doi: 10.1016/j.numecd.2008.09.002 – volume: 49 start-page: 1696 year: 2007 ident: 2022031218230567800_B2 article-title: A randomized, placebo-controlled trial assessing the effects of rosiglitazone on echocardiographic function and cardiac status in type 2 diabetic patients with New York Heart Association Functional Class I or II Heart Failure publication-title: J Am Coll Cardiol doi: 10.1016/j.jacc.2006.10.077 – volume: 41 start-page: 1529 year: 2003 ident: 2022031218230567800_B18 article-title: Efficacy of angiotensin-converting enzyme inhibitors and beta-blockers in the management of left ventricular systolic dysfunction according to race, gender, and diabetic status: a meta-analysis of major clinical trials publication-title: J Am Coll Cardiol doi: 10.1016/S0735-1097(03)00262-6 – start-page: 337 volume-title: Pharmacoepidemiology year: 2005 ident: 2022031218230567800_B5 article-title: The UK General Practice Research Database – volume: 54 start-page: 422 year: 2009 ident: 2022031218230567800_B16 article-title: Relationship of hemoglobin A1C and mortality in heart failure patients with diabetes publication-title: J Am Coll Cardiol doi: 10.1016/j.jacc.2009.04.049 – volume: 339 start-page: b4731 year: 2009 ident: 2022031218230567800_B9 article-title: Risk of cardiovascular disease and all cause mortality among patients with type 2 diabetes prescribed oral antidiabetes drugs: retrospective cohort study using UK general practice research database publication-title: BMJ doi: 10.1136/bmj.b4731 – volume: 51 start-page: 93 year: 2008 ident: 2022031218230567800_B13 article-title: Insulin-resistant cardiomyopathy: clinical evidence, mechanisms, and treatment options publication-title: J Am Coll Cardiol doi: 10.1016/j.jacc.2007.10.021 – volume: 146 start-page: 848 year: 2003 ident: 2022031218230567800_B19 article-title: Are beta-blockers as efficacious in patients with diabetes mellitus as in patients without diabetes mellitus who have chronic heart failure? A meta-analysis of large-scale clinical trials publication-title: Am Heart J doi: 10.1016/S0002-8703(03)00403-4 – volume: 46 start-page: 1019 year: 2005 ident: 2022031218230567800_B10 article-title: Impaired insulin sensitivity as an independent risk factor for mortality in patients with stable chronic heart failure publication-title: J Am Coll Cardiol doi: 10.1016/j.jacc.2005.02.093 – volume: 21 start-page: 1368 year: 2000 ident: 2022031218230567800_B11 article-title: Glucose and insulin abnormalities relate to functional capacity in patients with congestive heart failure publication-title: Eur Heart J doi: 10.1053/euhj.1999.2043 – volume: 147 start-page: 386 issue: 6 year: 2007 ident: 2022031218230567800_B21 article-title: Systematic review: comparative effectiveness and safety of oral medications for type 2 diabetes mellitus publication-title: Ann Intern Med doi: 10.7326/0003-4819-147-6-200709180-00178 – volume: 138 start-page: 938 year: 2003 ident: 2022031218230567800_B20 article-title: Applying evidence to patient care: from black and white to shades of grey publication-title: Ann Intern Med doi: 10.7326/0003-4819-138-11-200306030-00016 |
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| Snippet | OBJECTIVE: Diabetes and heart failure commonly coexist, and prior studies have suggested better outcomes with metformin than other antidiabetic agents. We... Diabetes and heart failure commonly coexist, and prior studies have suggested better outcomes with metformin than other antidiabetic agents. We designed this... |
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| SubjectTerms | Adrenergic beta-Antagonists Adrenergic beta-Antagonists - adverse effects Adrenergic beta-Antagonists - therapeutic use adverse effects Aged Aged, 80 and over Angiotensin-Converting Enzyme Inhibitors Angiotensin-Converting Enzyme Inhibitors - adverse effects Angiotensin-Converting Enzyme Inhibitors - therapeutic use Aspirin Aspirin - adverse effects Aspirin - therapeutic use beta-adrenergic antagonists Biological and medical sciences body mass index Case-Control Studies comorbidity complications Diabetes Diabetes Mellitus, Type 2 Diabetes Mellitus, Type 2 - complications Diabetes Mellitus, Type 2 - drug therapy Diabetes Mellitus, Type 2 - mortality Diabetes therapy Diabetes. Impaired glucose tolerance Digoxin Digoxin - adverse effects Digoxin - therapeutic use Drug therapy Endocrine pancreas. Apud cells (diseases) Endocrinopathies Etiopathogenesis. Screening. Investigations. Target tissue resistance Family medicine Female glucose Great Britain Heart failure Heart Failure - complications Heart Failure - drug therapy Heart Failure - mortality Humans Hypoglycemic Agents Hypoglycemic Agents - adverse effects Hypoglycemic Agents - therapeutic use insulin Male Medical research Medical sciences Medicine Medicine, Experimental Metabolic diseases metformin Metformin - adverse effects Metformin - therapeutic use Miscellaneous mortality noninsulin-dependent diabetes mellitus odds ratio Online databases Original Research Patient outcomes patients Practice Public health. Hygiene Public health. Hygiene-occupational medicine renal function Studies therapeutic use Type 2 diabetes United Kingdom |
| Title | Treatment of Type 2 Diabetes and Outcomes in Patients With Heart Failure: A Nested Case-Control Study From the U.K. General Practice Research Database |
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