Blog
About

7
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      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

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          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 m 2, 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 m 2.

          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.

          Article summary

          Article focus
          • To evaluate the risks of CVD, acidosis/serious infection and mortality associated with metformin and other glucose-lowering treatments, in a cohort of 51 675 type 2 diabetes patients and in subgroups with different degrees of renal impairment.

          Key messages
          • Metformin was associated with reduced risk of CVD, acidosis/serious infection and all-cause mortality compared with insulin and a reduced risk of all-cause mortality compared with other OHAs.

          • The effects were consistent in patients with renal impairment (eGFR 45–60 ml/min/1.73 m 2), and there were no increased risk of acidosis/serious infection even in patients with low renal function (eGFR 30–45 ml/min/1.73 m 2).

          Strengths and limitations of this study
          • A large cohort with comprehensive data on patient characteristics was studied.

          • A composite end point including diagnosis of acidosis, shock, acute renal failure and serious infections was used to evaluate the occurrence of lactic acidosis.

          Related collections

          Most cited references 30

          • Record: found
          • Abstract: found
          • Article: not found

          A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group.

          Serum creatinine concentration is widely used as an index of renal function, but this concentration is affected by factors other than glomerular filtration rate (GFR). To develop an equation to predict GFR from serum creatinine concentration and other factors. Cross-sectional study of GFR, creatinine clearance, serum creatinine concentration, and demographic and clinical characteristics in patients with chronic renal disease. 1628 patients enrolled in the baseline period of the Modification of Diet in Renal Disease (MDRD) Study, of whom 1070 were randomly selected as the training sample; the remaining 558 patients constituted the validation sample. The prediction equation was developed by stepwise regression applied to the training sample. The equation was then tested and compared with other prediction equations in the validation sample. To simplify prediction of GFR, the equation included only demographic and serum variables. Independent factors associated with a lower GFR included a higher serum creatinine concentration, older age, female sex, nonblack ethnicity, higher serum urea nitrogen levels, and lower serum albumin levels (P < 0.001 for all factors). The multiple regression model explained 90.3% of the variance in the logarithm of GFR in the validation sample. Measured creatinine clearance overestimated GFR by 19%, and creatinine clearance predicted by the Cockcroft-Gault formula overestimated GFR by 16%. After adjustment for this overestimation, the percentage of variance of the logarithm of GFR predicted by measured creatinine clearance or the Cockcroft-Gault formula was 86.6% and 84.2%, respectively. The equation developed from the MDRD Study provided a more accurate estimate of GFR in our study group than measured creatinine clearance or other commonly used equations.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            10-year follow-up of intensive glucose control in type 2 diabetes.

            During the United Kingdom Prospective Diabetes Study (UKPDS), patients with type 2 diabetes mellitus who received intensive glucose therapy had a lower risk of microvascular complications than did those receiving conventional dietary therapy. We conducted post-trial monitoring to determine whether this improved glucose control persisted and whether such therapy had a long-term effect on macrovascular outcomes. Of 5102 patients with newly diagnosed type 2 diabetes, 4209 were randomly assigned to receive either conventional therapy (dietary restriction) or intensive therapy (either sulfonylurea or insulin or, in overweight patients, metformin) for glucose control. In post-trial monitoring, 3277 patients were asked to attend annual UKPDS clinics for 5 years, but no attempts were made to maintain their previously assigned therapies. Annual questionnaires were used to follow patients who were unable to attend the clinics, and all patients in years 6 to 10 were assessed through questionnaires. We examined seven prespecified aggregate clinical outcomes from the UKPDS on an intention-to-treat basis, according to previous randomization categories. Between-group differences in glycated hemoglobin levels were lost after the first year. In the sulfonylurea-insulin group, relative reductions in risk persisted at 10 years for any diabetes-related end point (9%, P=0.04) and microvascular disease (24%, P=0.001), and risk reductions for myocardial infarction (15%, P=0.01) and death from any cause (13%, P=0.007) emerged over time, as more events occurred. In the metformin group, significant risk reductions persisted for any diabetes-related end point (21%, P=0.01), myocardial infarction (33%, P=0.005), and death from any cause (27%, P=0.002). Despite an early loss of glycemic differences, a continued reduction in microvascular risk and emergent risk reductions for myocardial infarction and death from any cause were observed during 10 years of post-trial follow-up. A continued benefit after metformin therapy was evident among overweight patients. (UKPDS 80; Current Controlled Trials number, ISRCTN75451837.) 2008 Massachusetts Medical Society
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Global and societal implications of the diabetes epidemic.

              Changes in human behaviour and lifestyle over the last century have resulted in a dramatic increase in the incidence of diabetes worldwide. The epidemic is chiefly of type 2 diabetes and also the associated conditions known as 'diabesity' and 'metabolic syndrome'. In conjunction with genetic susceptibility, particularly in certain ethnic groups, type 2 diabetes is brought on by environmental and behavioural factors such as a sedentary lifestyle, overly rich nutrition and obesity. The prevention of diabetes and control of its micro- and macrovascular complications will require an integrated, international approach if we are to see significant reduction in the huge premature morbidity and mortality it causes.
                Bookmark

                Author and article information

                Affiliations
                [1 ]Department of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
                [2 ]Centre of Registers in Region Västra Götaland, Gothenburg, Sweden
                [3 ]Department of Public Health and Community Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
                [4 ]Department of Public Health and Caring Science/Geriatrics, Uppsala University, Sweden
                [5 ]Medical Products Agency, Uppsala, Sweden
                [6 ]Department of Public Health and Caring Science/Family Medicine and Clinical Epidemiology, Uppsala University, Sweden
                Author notes
                Correspondence to Dr Nils Ekström; nils.ekstrom@ 123456gu.se
                Journal
                BMJ Open
                BMJ Open
                bmjopen
                bmjopen
                BMJ Open
                BMJ Group (BMA House, Tavistock Square, London, WC1H 9JR )
                2044-6055
                2012
                13 July 2012
                13 July 2012
                : 2
                : 4
                3400073
                22798258
                bmjopen-2012-001076
                10.1136/bmjopen-2012-001076
                © 2012, Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

                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.

                Product
                Categories
                Diabetes and Endocrinology
                Research
                1506
                1688
                1692
                1723
                1683

                Medicine

                Comments

                Comment on this article