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report no conflicts of interest. C. J. C. had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis
R. Ruiter, L. Visser, M. Herk-Sukel, J. Coebergh, H. Haak, P. Geelhoed-Duijvestijn, S. Straus, R. Herings, B. Stricker (2011)
Lower Risk of Cancer in Patients on Metformin in Comparison With Those on Sulfonylurea DerivativesDiabetes Care, 35
T. Forst, M. Hanefeld, S. Jacob, Guido Moeser, Gero Schwenk, A. Pfützner, A. Haupt (2013)
Association of sulphonylurea treatment with all-cause and cardiovascular mortality: A systematic review and meta-analysis of observational studiesDiabetes & Vascular Disease Research, 10
S. Bowker, Yutaka Yasui, P. Veugelers, J. Johnson (2010)
Glucose-lowering agents and cancer mortality rates in type 2 diabetes: assessing effects of time-varying exposureDiabetologia, 53
Jeffrey Johnson, S. Majumdar, S. Simpson, E. Toth (2002)
Decreased mortality associated with the use of metformin compared with sulfonylurea monotherapy in type 2 diabetes.Diabetes care, 25 12
Turner Turner, Nartey Nartey, Stafford Stafford, Singh Singh, Caleb Caleb (2014)
Ambulatory treatment of type 2 diabetes mellitus in the United States, 1997–2012Diabetes Care, 37
D. Soranna, L. Scotti, A. Zambon, C. Bosetti, G. Grassi, A. Catapano, C. Vecchia, G. Mancia, G. Corrao (2012)
Cancer risk associated with use of metformin and sulfonylurea in type 2 diabetes: a meta-analysis.The oncologist, 17 6
Silver Spring: U.S. Food and Drug Administration
Roumie Roumie, Hung Hung, Greevy Greevy (2012)
Comparative effectiveness of sulfonylurea and metformin monotherapy on cardiovascular events in type 2 diabetes mellitus: a cohort studyAnn Intern Med, 157
A. Terzic, A. Jahangir, Y. Kurachi (1995)
Cardiac ATP-sensitive K+ channels: regulation by intracellular nucleotides and K+ channel-opening drugs.The American journal of physiology, 269 3 Pt 1
S. Holden, C. Currie (2014)
Mortality risk with sulphonylureas compared to metforminDiabetes, 16
B. Thakkar, K. Aronis, Maria Vamvini, Kelsey Shields, C. Mantzoros (2013)
Metformin and sulfonylureas in relation to cancer risk in type II diabetes patients: a meta-analysis using primary data of published studies.Metabolism: clinical and experimental, 62 7
C. Morgan, C. Poole, M. Evans, A. Barnett, S. Jenkins-Jones, C. Currie (2012)
What next after metformin? A retrospective evaluation of the outcome of second-line, glucose-lowering therapies in people with type 2 diabetes.The Journal of clinical endocrinology and metabolism, 97 12
J. Evans, S. Ogston, A. Emslie-Smith, A. Morris (2006)
Risk of mortality and adverse cardiovascular outcomes in type 2 diabetes: a comparison of patients treated with sulfonylureas and metforminDiabetologia, 49
H. Qiu, H. Qiu, G. Rhoads, J. Berlin, S. Marcella, K. Demissie (2013)
Initial metformin or sulphonylurea exposure and cancer occurrence among patients with type 2 diabetes mellitusDiabetes, 15
M. Hsieh, Tzu-Chi Lee, S. Cheng, S. Tu, M. Yen, C. Tseng (2012)
The Influence of Type 2 Diabetes and Glucose-Lowering Therapies on Cancer Risk in the TaiwaneseExperimental Diabetes Research, 2012
M. Harris, R. Klein, T. Welborn, M. Knuiman (1992)
Onset of NIDDM occurs at Least 4–7 yr Before Clinical DiagnosisDiabetes Care, 15
(1998)
Study (UKPDS) Group
C. Morgan, J. Mukherjee, S. Jenkins-Jones, S. Holden, C. Currie (2014)
Combination therapy with metformin plus sulphonylureas versus metformin plus DPP‐4 inhibitors: association with major adverse cardiovascular events and all‐cause mortalityDiabetes, 16
J. Hollowell (1997)
The General Practice Research Database: quality of morbidity data.Population trends, 87
C. Roumie, A. Hung, R. Greevy, Carlos Grijalva, Xulei Liu, H. Murff, T. Elasy, M. Griffin (2012)
Comparative Effectiveness of Sulfonylurea and Metformin Monotherapy on Cardiovascular Events in Type 2 Diabetes MellitusAnnals of Internal Medicine, 157
W. Sauerbrei (1999)
The Use of Resampling Methods to Simplify Regression Models in Medical StatisticsJournal of the Royal Statistical Society: Series C (Applied Statistics), 48
2011 National Diabetes Fact Sheet 2011 Diabetes in the UK 2012 : Key statistics on diabetes 2012
T. Schramm, G. Gislason, A. Vaag, J. Rasmussen, F. Folke, M. Hansen, E. Fosbøl, L. Køber, M. Norgaard, M. Madsen, P. Hansen, C. Torp-Pedersen (2011)
Mortality and cardiovascular risk associated with different insulin secretagogues compared with metformin in type 2 diabetes, with or without a previous myocardial infarction: a nationwide study.European heart journal, 32 15
N. Sturgess, D. Cook, Michael Ashford, C. Hales (1985)
THE SULPHONYLUREA RECEPTOR MAY BE AN ATP-SENSITIVE POTASSIUM CHANNELThe Lancet, 326
S. Inzucchi, R. Bergenstal, J. Buse, M. Diamant, E. Ferrannini, M. Nauck, A. Peters, A. Tsapas, R. Wender, D. Matthews (2012)
Management of Hyperglycemia in Type 2 Diabetes: A Patient-Centered ApproachDiabetes Care, 35
Caleb Alexander, Lydia Turner, D. Nartey, R. Stafford, Sonal Singh, G. ALEXANDER (2014)
Ambulatory Treatment of Type 2 Diabetes in the U.S., 1997–2012Diabetes Care, 37
D. Kirpichnikov, Samy McFarlane, J. Sowers (2002)
Metformin: An UpdateAnnals of Internal Medicine, 137
A. Kooy, J. Jager, P. Lehert, D. Bets, M. Wulffelé, A. Donker, C. Stehouwer (2009)
Long-term effects of metformin on metabolism and microvascular and macrovascular disease in patients with type 2 diabetes mellitus.Archives of internal medicine, 169 6
R. Turner, R. Holman, I. Stratton, C. Cull, D. Matthews, S. Manley, V. Frighi, D. Wright, A. Neil, E. Kohner, H. Mcelroy, C. Fox, D. Hadden, Grp Ukpds. (1998)
Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34)The Lancet, 352
M. Charlson, P. Pompei, Kathy Ales, C. MacKenzie (1987)
A new method of classifying prognostic comorbidity in longitudinal studies: development and validation.Journal of chronic diseases, 40 5
is a director of Pharmatelligence, a research consultancy receiving funding from pharmaceutical companies
C. Currie, C. Poole, E. Gale (2009)
The influence of glucose-lowering therapies on cancer risk in type 2 diabetesDiabetologia, 52
M. Franciosi, G. Lucisano, E. Lapice, G. Strippoli, F. Pellegrini, A. Nicolucci (2013)
Metformin Therapy and Risk of Cancer in Patients with Type 2 Diabetes: Systematic ReviewPLoS ONE, 8
Richard Stevens, R. Ali, C. Bankhead, M. Bethel, B. Cairns, R. Camisasca, F. Crowe, A. Farmer, S. Harrison, J. Hirst, Philip Home, S. Kahn, J. Mclellan, R. Perera, A. Plüddemann, A. Ramachandran, N. Roberts, P. Rose, A. Schweizer, G. Viberti, R. Holman (2012)
Cancer outcomes and all-cause mortality in adults allocated to metformin: systematic review and collaborative meta-analysis of randomised clinical trialsDiabetologia, 55
Sunil Rao (2003)
Regression Modeling Strategies: With Applications to Linear Models, Logistic Regression, and Survival AnalysisJournal of the American Statistical Association, 98
C. Nordin (2010)
The case for hypoglycaemia as a proarrhythmic event: basic and clinical evidenceDiabetologia, 53
J. Johnson, S. Simpson, E. Toth, S. Majumdar (2005)
Reduced cardiovascular morbidity and mortality associated with metformin use in subjects with Type 2 diabetesDiabetic Medicine, 22
C. Lamanna, M. Monami, N. Marchionni, E. Mannucci (2011)
Effect of metformin on cardiovascular events and mortality: a meta‐analysis of randomized clinical trialsDiabetes, 13
L. Azoulay, Verena Schneider-Lindner, S. Dell'aniello, A. Schiffrin, S. Suissa (2010)
Combination therapy with sulfonylureas and metformin and the prevention of death in type 2 diabetes: a nested case‐control studyPharmacoepidemiology and Drug Safety, 19
Ruiter Ruiter, Visser Visser, van Herk‐Sukel van Herk‐Sukel (2012)
Lower risk of cancer in patients on metformin in comparison with those on sulfonylurea derivatives: results from a large population‐based follow‐up studyDiabetes Care, 35
E. González, S. Johansson, M. Wallander, L. Rodríguez (2009)
Trends in the prevalence and incidence of diabetes in the UK: 1996–2005Journal of Epidemiology & Community Health, 63
K. Pantalone, M. Kattan, Changhong Yu, B. Wells, S. Arrigain, Anil Jain, A. Atreja, R. Zimmerman (2012)
Increase in overall mortality risk in patients with type 2 diabetes receiving glipizide, glyburide or glimepiride monotherapy versus metformin: a retrospective analysisDiabetes, 14
Nada Khan, S. Harrison, P. Rose (2010)
Validity of diagnostic coding within the General Practice Research Database: a systematic review.The British journal of general practice : the journal of the Royal College of General Practitioners, 60 572
S. Inzucchi, R. Bergenstal, J. Buse, M. Diamant, E. Ferrannini, M. Nauck, A. Peters, A. Tsapas, R. Wender, David Matthews, David Matthews, David Matthews (2013)
Erratum to: Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)Diabetologia, 56
Jie Hong, Yifei Zhang, S. Lai, Ankang Lv, Q. Su, Yan Dong, Zhiguang Zhou, Wei-li Tang, Jiajun Zhao, Lianqun Cui, D. Zou, Dawang Wang, Hong Li, Chao Liu, Guo-ting Wu, Jie Shen, Dalong Zhu, Weiqing Wang, Weifeng Shen, G. Ning (2013)
Effects of Metformin Versus Glipizide on Cardiovascular Outcomes in Patients With Type 2 Diabetes and Coronary Artery DiseaseDiabetes Care, 36
P. Beisswenger, S. Howell, Allison Touchette, S. Lal, B. Szwergold (1999)
Metformin reduces systemic methylglyoxal levels in type 2 diabetes.Diabetes, 48 1
C. Morgan, J. Mukherjee, S. Jenkins-Jones, S. Holden, C. Currie (2014)
Association between first‐line monotherapy with sulphonylurea versus metformin and risk of all‐cause mortality and cardiovascular events: a retrospective, observational studyDiabetes, 16
Aims Clinical and observational studies have shown an increased risk of cardiovascular events and death associated with sulphonylureas versus metformin. However, it has never been determined whether this was due to the beneficial effects of metformin or detrimental effects of sulphonylureas. The objective of this study was therefore to compare all‐cause mortality in diabetic patients treated first‐line with either sulphonylurea or metformin monotherapy with that in matched individuals without diabetes. Methods We used retrospective observational data from the UK Clinical Practice Research Datalink (CPRD) from 2000. Subjects with type 2 diabetes who progressed to first‐line treatment with metformin or sulphonylurea monotherapy were selected and matched to people without diabetes. Progression to all‐cause mortality was compared using parametric survival models that included a range of relevant co‐variables. Results We identified 78 241 subjects treated with metformin, 12 222 treated with sulphonylurea, and 90 463 matched subjects without diabetes. This resulted in a total, censored follow‐up period of 503 384 years. There were 7498 deaths in total, representing unadjusted mortality rates of 14.4 and 15.2, and 50.9 and 28.7 deaths per 1000 person‐years for metformin monotherapy and their matched controls, and sulphonylurea monotherapy and their matched controls, respectively. With reference to observed survival in diabetic patients initiated with metformin monotherapy (survival time ratio (STR) = 1.0), adjusted median survival time was 15% lower (STR = 0.85, 95% CI 0.81–0.90) in matched individuals without diabetes and 38% lower (0.62, 0.58–0.66) in diabetic patients treated with sulphonylurea monotherapy. Conclusions Patients with type 2 diabetes initiated with metformin monotherapy had longer survival than did matched, non‐diabetic controls. Those treated with sulphonylurea had markedly reduced survival compared with both matched controls and those receiving metformin monotherapy. This supports the position of metformin as first‐line therapy and implies that metformin may confer benefit in non‐diabetes. Sulphonylurea remains a concern.
Diabetes Obesity and Metabolism – Wiley
Published: Nov 1, 2014
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