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      Dapagliflozin is associated with lower risk of cardiovascular events and all‐cause mortality in people with type 2 diabetes (CVD‐REAL Nordic) when compared with dipeptidyl peptidase‐4 inhibitor therapy: A multinational observational study

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          To compare the sodium‐glucose‐cotransporter‐2 (SGLT‐2) inhibitor dapagliflozin with dipeptidyl peptidase‐4 (DPP‐4) inhibitors with regard to risk associations with major adverse cardiovascular (CV) events (MACE; non‐fatal myocardial infarction, non‐fatal stroke or cardiovascular mortality), hospitalization for heart failure (HHF), atrial fibrillation and severe hypoglycaemia in patients with type 2 diabetes (T2D) in a real‐world setting.


          All patients with T2D prescribed glucose‐lowering drugs (GLDs) during 2012 to 2015 were identified in nationwide registries in Denmark, Norway and Sweden. Patients were divided into two groups: new users of dapagliflozin and new users of DPP‐4 inhibitors, matched 1:3 by propensity score, calculated by patient characteristics, comorbidities and drug treatment. Cox survival models were used to estimate hazard ratio (HR) per country separately, and a weighted average was calculated.


          After matching, a total of 40 908 patients with T2D were identified as new users of dapagliflozin (n = 10 227) or a DPP‐4 inhibitor (n = 30 681). The groups were well balanced at baseline; their mean age was 61 years and 23% had CV disease. The mean follow‐up time was 0.95 years, with a total of 38 760 patient‐years. Dapagliflozin was associated with a lower risk of MACE, HHF and all‐cause mortality compared with DPP‐4 inhibitors: HRs 0.79 (95% confidence interval [CI] 0.67‐0.94), 0.62 (95% CI 0.50‐0.77), and 0.59 (95% CI 0.49‐0.72), respectively. Numerically lower, but non‐significant HRs were observed for myocardial infarction (0.91 [95% CI 0.72‐1.16]), stroke (0.79 [95% CI 0.61‐1.03]) and CV mortality (0.76 [95% CI 0.53‐1.08]) Neutral associations with atrial fibrillation and severe hypoglycaemia were observed.


          Dapagliflozin was associated with lower risks of CV events and all‐cause mortality compared with DPP‐4 inhibitors in a real‐world clinical setting and a broad T2D population.

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          Most cited references 34

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          Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes.

          The effects of empagliflozin, an inhibitor of sodium-glucose cotransporter 2, in addition to standard care, on cardiovascular morbidity and mortality in patients with type 2 diabetes at high cardiovascular risk are not known.
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            External review and validation of the Swedish national inpatient register

            Background The Swedish National Inpatient Register (IPR), also called the Hospital Discharge Register, is a principal source of data for numerous research projects. The IPR is part of the National Patient Register. The Swedish IPR was launched in 1964 (psychiatric diagnoses from 1973) but complete coverage did not begin until 1987. Currently, more than 99% of all somatic (including surgery) and psychiatric hospital discharges are registered in the IPR. A previous validation of the IPR by the National Board of Health and Welfare showed that 85-95% of all diagnoses in the IPR are valid. The current paper describes the history, structure, coverage and quality of the Swedish IPR. Methods and results In January 2010, we searched the medical databases, Medline and HighWire, using the search algorithm "validat* (inpatient or hospital discharge) Sweden". We also contacted 218 members of the Swedish Society of Epidemiology and an additional 201 medical researchers to identify papers that had validated the IPR. In total, 132 papers were reviewed. The positive predictive value (PPV) was found to differ between diagnoses in the IPR, but is generally 85-95%. Conclusions In conclusion, the validity of the Swedish IPR is high for many but not all diagnoses. The long follow-up makes the register particularly suitable for large-scale population-based research, but for certain research areas the use of other health registers, such as the Swedish Cancer Register, may be more suitable.
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              Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes

              Background Canagliflozin is a sodium-glucose cotransporter 2 inhibitor that reduces glycemia as well as blood pressure, body weight, and albuminuria in people with diabetes. We report the effects of treatment with canagliflozin on cardiovascular, renal, and safety outcomes. Methods The CANVAS Program integrated data from two trials involving a total of 10,142 participants with type 2 diabetes and high cardiovascular risk. Participants in each trial were randomly assigned to receive canagliflozin or placebo and were followed for a mean of 188.2 weeks. The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Results The mean age of the participants was 63.3 years, 35.8% were women, the mean duration of diabetes was 13.5 years, and 65.6% had a history of cardiovascular disease. The rate of the primary outcome was lower with canagliflozin than with placebo (occurring in 26.9 vs. 31.5 participants per 1000 patient-years; hazard ratio, 0.86; 95% confidence interval [CI], 0.75 to 0.97; P<0.001 for noninferiority; P=0.02 for superiority). Although on the basis of the prespecified hypothesis testing sequence the renal outcomes are not viewed as statistically significant, the results showed a possible benefit of canagliflozin with respect to the progression of albuminuria (hazard ratio, 0.73; 95% CI, 0.67 to 0.79) and the composite outcome of a sustained 40% reduction in the estimated glomerular filtration rate, the need for renal-replacement therapy, or death from renal causes (hazard ratio, 0.60; 95% CI, 0.47 to 0.77). Adverse reactions were consistent with the previously reported risks associated with canagliflozin except for an increased risk of amputation (6.3 vs. 3.4 participants per 1000 patient-years; hazard ratio, 1.97; 95% CI, 1.41 to 2.75); amputations were primarily at the level of the toe or metatarsal. Conclusions In two trials involving patients with type 2 diabetes and an elevated risk of cardiovascular disease, patients treated with canagliflozin had a lower risk of cardiovascular events than those who received placebo but a greater risk of amputation, primarily at the level of the toe or metatarsal. (Funded by Janssen Research and Development; CANVAS and CANVAS-R numbers, NCT01032629 and NCT01989754 , respectively.).

                Author and article information

                Diabetes Obes Metab
                Diabetes Obes Metab
                Diabetes, Obesity & Metabolism
                Blackwell Publishing Ltd (Oxford, UK )
                08 September 2017
                February 2018
                : 20
                : 2 ( doiID: 10.1111/dom.2018.20.issue-2 )
                : 344-351
                [ 1 ] Steno Diabetes Centre Copenhagen Denmark
                [ 2 ] Karolinska Institutet, Södersjukhuset Stockholm Sweden
                [ 3 ] Oslo University Hospital Oslo Norway
                [ 4 ] Statisticon AB Uppsala Sweden
                [ 5 ] AstraZeneca Cambridge UK
                [ 6 ] Uppsala University Uppsala Sweden
                [ 7 ] Karolinska Institutet Stockholm Sweden
                [ 8 ] Capio S:t Görans Hospital Stockholm Sweden
                [ 9 ] AstraZeneca Nordic‐Baltic Oslo Norway
                [ 10 ] University of Oslo Oslo Norway
                Author notes
                [* ] Correspondence

                Dr Johan Bodegard, AstraZeneca Nordic‐Baltic, 0601 Oslo, Norway. Email: johan.bodegard@

                © 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                Figures: 2, Tables: 2, Pages: 8, Words: 5965
                Funded by: AstraZeneca AB
                Original Article
                Original Articles
                Custom metadata
                February 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version= mode:remove_FC converted:14.02.2018


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