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Effectiveness and safety of metformin in 51 675 patients with type 2 diabetes and different levels of renal function: a cohort study from the Swedish National Diabetes Register
  1. Nils Ekström1,
  2. Linus Schiöler2,3,
  3. Ann-Marie Svensson2,
  4. Katarina Eeg-Olofsson1,
  5. Junmei Miao Jonasson2,
  6. Björn Zethelius4,5,
  7. Jan Cederholm6,
  8. Björn Eliasson1,
  9. Soffia Gudbjörnsdottir1,2
  1. 1Department of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
  2. 2Centre of Registers in Region Västra Götaland, Gothenburg, Sweden
  3. 3Department of Public Health and Community Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
  4. 4Department of Public Health and Caring Science/Geriatrics, Uppsala University, Sweden
  5. 5Medical Products Agency, Uppsala, Sweden
  6. 6Department of Public Health and Caring Science/Family Medicine and Clinical Epidemiology, Uppsala University, Sweden
  1. Correspondence to Dr Nils Ekström; nils.ekstrom{at}gu.se

Abstract

Objective To evaluate the effectiveness and safety of metformin use in clinical practice in a large sample of pharmacologically treated patients with type 2 diabetes and different levels of renal function.

Design Observational study between July 2004 and December 2010, mean follow-up 3.9 years.

Setting Hospital outpatient clinics and primary care in Sweden.

Participants 51 675 men and women with type 2 diabetes, registered in the Swedish National Diabetes Register, and on continuous glucose-lowering treatment with oral hypoglycaemic agents (OHAs) or insulin.

Main outcome measures Risks of cardiovascular disease (CVD), all-cause mortality and acidosis/serious infection, associated with each treatment regimens, were analysed in all patients and in subgroups with different estimated glomerular filtration rate (eGFR) intervals. Covariance adjustment and propensity scores were used to adjust for several baseline risk factors and characteristics at Cox regression.

Results Compared with metformin in monotherapy, HRs for fatal/non-fatal CVD and all-cause mortality with all other OHAs combined (approximately 80% sulphonylureas) in monotherapy were 1.02 (95% CI 0.93 to 1.12) and 1.13 (1.01 to 1.27), while 1.18 (1.07 to 1.29) and 1.34 (1.19 to 1.50) with insulin in monotherapy, adjusting using propensity scores. Metformin, compared with any other treatment, showed reduced risks of acidosis/serious infection (adjusted HR 0.85, 95% CI 0.74 to 0.97) and all-cause mortality (HR 0.87, 95% CI 0.77 to 0.99), in patients with eGFR 45–60 ml/min/1.73 m2, and no increased risks of all-cause mortality, acidosis/serious infection or CVD were found in patients with eGFR 30–45 ml/min/1.73 m2.

Conclusions Metformin showed lower risk than insulin for CVD and all-cause mortality and slightly lower risk for all-cause mortality compared with other OHA, in these 51 675 patients followed for 4 years. Patients with renal impairment showed no increased risk of CVD, all-cause mortality or acidosis/serious infection. In clinical practice, the benefits of metformin use clearly outbalance the risk of severe side effects.

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.

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Footnotes

  • To cite: Ekström N, Schiöler L, Svensson A-M, et al. Effectiveness and safety of metformin in 51 675 patients with type 2 diabetes and different levels of renal function: a cohort study from the Swedish National Diabetes Register. BMJ Open 2012;2:e001076. doi:10.1136/bmjopen-2012-001076

  • Contributors NE, LS, BZ, JC, A-MS, JMJ, KE-O, SG and BE contributed to the conception and design. LS, JC and A-MS contributed to the acquisition of data and performed the calculations. LS, NE, JC, BZ, SG, A-MS and BE contributed to the analysis and interpretation of data. NE and BE contributed to drafting the article. NE, BE, BZ, JC, A-MS, LS, KE-O, SG and JMJ contributed to revising the article critically for important intellectual content and final approval of the version to be submitted.

  • Funding The Region Västra Götaland and the Swedish Association of Local Authorities and Regions fund the National Diabetes Register (NDR). The NDR is supported by the Swedish Society for Diabetology, and the Swedish Diabetes Association. LS, A-MS, JMJ, and SG were also supported by an unrestricted research grant from BMS, France. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

  • Disclaimer BZ is employed by the Medical Products Agency (MPA), Uppsala, Sweden. BZ has not received any financial support or other benefits from BMS, France, or any commercial sponsor. Results and views of the present study represent the authors and not necessarily any official views of the MPA where BZ is employed.

  • Competing interests BE has served as a lecturer for all pharmacological companies manufacturing glucose-lowering agents and participated in advisory boards for Eli Lilly Sweden AB and Eli Lilly & Co, Sanofi-aventis, Sweden, Boehringer Ingelheim AB, Sweden, and MSD, Sweden.

  • Ethics approval Ethics approval was provided by the central ethical review board at the University of Gothenburg.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement No additional data available.

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