| 1. |
- Adamsson Eryd, Samuel, et al.
(författare)
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Blood pressure and complications in individuals with type 2 diabetes and no previous cardiovascular disease: national population based cohort study
- 2016
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Ingår i: Bmj-British Medical Journal. - : BMJ. - 1756-1833. ; 354
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES To compare the risk associated with systolic blood pressure that meets current recommendations (that is, below 140 mm Hg) with the risk associated with lower levels in patients who have type 2 diabetes and no previous cardiovascular disease. Population based cohort study with nationwide clinical registries, 2006-12. The mean follow-up was 5.0 years. 187 106 patients registered in the Swedish national diabetes register who had had type 2 diabetes for at least a year, age 75 or younger, and with no previous cardiovascular or other major disease. Clinical events were obtained from the hospital discharge and death registers with respect to acute myocardial infarction, stroke, a composite of acute myocardial infarction and stroke (cardiovascular disease), coronary heart disease, heart failure, and total mortality. Hazard ratios were estimated for different levels of baseline systolic blood pressure with clinical characteristics and drug prescription data as covariates. The group with the lowest systolic blood pressure (110-119 mm Hg) had a significantly lower risk of non-fatal acute myocardial infarction (adjusted hazard ratio 0.76, 95% confidence interval 0.64 to 0.91; P=0.003), total acute myocardial infarction (0.85, 0.72 to 0.99; P=0.04), non-fatal cardiovascular disease (0.82, 0.72 to 0.93; P=0.002), total cardiovascular disease (0.88, 0.79 to 0.99; P=0.04), and non-fatal coronary heart disease (0.88, 0.78 to 0.99; P=0.03) compared with the reference group (130-139 mm Hg). There was no indication of a J shaped relation between systolic blood pressure and the endpoints, with the exception of heart failure and total mortality. Lower systolic blood pressure than currently recommended is associated with significantly lower risk of cardiovascular events in patients with type 2 diabetes. The association between low blood pressure and increased mortality could be due to concomitant disease rather than antihypertensive treatment.
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| 2. |
- Ludvigsson, Jonas F., 1969-, et al.
(författare)
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Periconception glycaemic control in women with type 1 diabetes and risk of major birth defects: population based cohort study in Sweden
- 2018
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Ingår i: Bmj-British Medical Journal. - : BMJ. - 1756-1833 .- 0959-8138. ; 362
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To examine the association between maternal type 1 diabetes and the risk of major birth defects according to levels of glycated haemoglobin (HbA1C) within three months before or after estimated conception. Population based historical cohort study using nationwide health registers. 2458 singleton liveborn infants of mothers with type 1 diabetes and a glycated haemoglobin measurement within three months before or after estimated conception and 1 159 865 infants of mothers without diabetes. Major cardiac and non-cardiac birth defects according to glycated haemoglobin levels. 122 cases of major cardiac defects were observed among 2458 infants of mothers with type 1 diabetes. Compared with 15 cases of major cardiac defects per 1000 infants of mothers without diabetes, the rates among infants of mothers with type 1 diabetes were 33 per 1000 for a glycated haemoglobin level of <6.5% (adjusted risk ratio 2.17, 95% confidence interval 1.37 to 3.42), 49 per 1000 for 6.5% to <7.8% (3.17, 2.45 to 4.11), 44 per 1000 for 7.8% to <9.1% (2.79, 1.90 to 4.12), and 101 per 1000 for >= 9.1% (6.23, 4.32 to 9.00). The corresponding adjusted risk differences were 17 (5 to 36), 32 (21 to 46), 26 (13 to 46), and 77 (49 to 118) cases of major cardiac defects per 1000 infants, respectively. 50 cases of major non-cardiac defects were observed among infants of mothers with type 1 diabetes. Compared with 18 cases of major non-cardiac defects per 1000 infants of mothers without diabetes, the rates among infants of mothers with type 1 diabetes were 22 per 1000 for a glycated haemoglobin level of <6.5% (adjusted risk ratio 1.18, 0.68 to 2.07), 19 per 1000 for 6.5% to <7.8% (1.01, 0.66 to 1.54), 17 per 1000 for 7.8% to <9.1% (0.89, 0.46 to 1.69), and 32 per 1000 for >= 9.1%(1.68, 0.85 to 3.33). Among liveborn infants of mothers with type 1 diabetes, increasingly worse glycaemic control in the three months before or after estimated conception was associated with a progressively increased risk of major cardiac defects. Even with glycated haemoglobin within target levels recommended by guidelines (<6.5%), the risk of major cardiac defects was increased more than twofold. The risk of major non-cardiac defects was not statistically significantly increased at any of the four glycated haemoglobin levels examined; the study had limited statistical power for this outcome and was based on live births only.
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| 3. |
- Pasternak, Bjorn, et al.
(författare)
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Glucagon-like peptide 1 receptor agonist use and risk of thyroid cancer: Scandinavian cohort study
- 2024
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Ingår i: BMJ-BRITISH MEDICAL JOURNAL. - 0959-535X .- 1756-1833. ; 385
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To investigate whether use of glucagon-like peptide 1 (GLP1) receptor agonists is associated with increased risk of thyroid cancer. DESIGN Scandinavian cohort study. SETTING Denmark, Norway, and Sweden, 2007-21. PARTICIPANTS Patients who started GLP1 receptor agonist treatment were compared with patients who started dipeptidyl peptidase 4 (DPP4) inhibitor treatment, and in an additional analysis, patients who started sodiumglucose cotransporter 2 (SGLT2) inhibitor treatment. MAIN OUTCOME MEASURES Thyroid cancer identified from nationwide cancer registers. An active -comparator new user study design was used to minimise risks of confounding and time related biases from using real world studies of drug effects. Cox regression was used to estimate hazard ratios, controlling for potential confounders with propensity score weighting. RESULTS The mean follow-up time was 3.9 years (standard deviation 3.5 years) in the GLP1 receptor agonist group and 5.4 years (standard deviation 3.5 years) in the DPP4 inhibitor group. 76 of 145 410 patients (incidence rate 1.33 events per 10 000 person years) treated with GLP1 receptor agonists and 184 of 291 667 patients (incidence rate 1.46 events per 10 000 person years) treated with DPP4 inhibitors developed thyroid cancer. GLP1 receptor agonist use was not associated with increased risk of thyroid cancer (hazard ratio 0.93, 95% confidence interval 0.66 to 1.31; rate difference -0.13, 95% confidence interval -0.61 to 0.36 events per 10 000 person years). The hazard ratio for medullary thyroid cancer was 1.19 (0.37 to 3.86). In the additional analysis comparing the GLP1 receptor agonist group with the SGLT2 inhibitor group, the hazard ratio for thyroid cancer was 1.16 (0.65 to 2.05). CONCLUSIONS In this large cohort study using nationwide data from three countries, GLP1 receptor agonist use was not associated with a substantially increased risk of thyroid cancer over a mean follow-up of 3.9 years. In the main analysis comparing GLP1 receptor agonists with DPP4 inhibitors, the upper limit of the confidence interval was consistent with no more than a 31% increase in relative risk.
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| 4. |
- Pasternak, B., et al.
(författare)
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Use of sodium-glucose co-transporter 2 inhibitors and risk of serious renal events: Scandinavian cohort study
- 2020
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Ingår i: Bmj-British Medical Journal. - : BMJ. - 1756-1833. ; 369
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To assess the association between use of sodium-glucose co-transporter 2 (SGLT2) inhibitors and risk of serious renal events in data from routine clinical practice. DESIGN Cohort study using an active comparator, new user design and nationwide register data. SETTING Sweden, Denmark, and Norway, 2013-18. PARTICIPANTS Cohort of 29 887 new users of SGLT2 inhibitors (follow-up time: dapagliflozin 66.1%; empagliflozin 32.6%; canagliflozin 1.3%) and 29 887 new users of an active comparator, dipeptidyl peptidase-4 inhibitors, matched 1:1 on the basis of a propensity score with 57 variables. Mean follow-up time was 1.7 (SD 1.0) years. EXPOSURES SGLT2 inhibitors versus dipeptidyl peptidase-4 inhibitors, defined by filled prescriptions and analysed according to intention to treat. MAIN OUTCOME MEASURES The main outcome was serious renal events, a composite including renal replacement therapy, death from renal causes, and hospital admission for renal events. Secondary outcomes were the individual components of the main outcome. RESULTS The mean age of the study population was 61.3 (SD 10.5) years; 11 108 (19%) had cardiovascular disease, and 1974 (3%) had chronic kidney disease. Use of SGLT2 inhibitors, compared with dipeptidyl peptidase-4 inhibitors, was associated with a reduced risk of serious renal events (2.6 events per 1000 person years versus 6.2 events per 1000 person years; hazard ratio 0.42 (95% confidence interval 0.34 to 0.53); absolute difference -3.6 (-4.4 to -2.8) events per 1000 person years). In secondary outcome analyses, the hazard ratio for use of SGLT2 inhibitors versus dipeptidyl peptidase-4 inhibitors was 0.32 (0.22 to 0.47) for renal replacement therapy, 0.41 (0.32 to 0.52) for hospital admission for renal events, and 0.77 (0.26 to 2.23) for death from renal causes. In sensitivity analyses in each of the Swedish and Danish parts of the cohort, the model was further adjusted for glycated haemoglobin and estimated glomerular filtration rate (Sweden and Denmark) and for blood pressure, body mass index, and smoking (Sweden only); in these analyses, the hazard ratio moved from 0.41 (0.26 to 0.66) to 0.50 (0.31 to 0.81) in Sweden and from 0.42 (0.32 to 0.56) to 0.55 (0.41 to 0.74) in Denmark. CONCLUSIONS In this analysis using nationwide data from three countries, use of SGLT2 inhibitors, compared with dipeptidyl peptidase-4 inhibitors, was associated with a significantly reduced risk of serious renal events.
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| 5. |
- Pasternak, B., et al.
(författare)
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Use of sodium glucose cotransporter 2 inhibitors and risk of major cardiovascular events and heart failure: Scandinavian register based cohort study
- 2019
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Ingår i: Bmj-British Medical Journal. - : BMJ. - 1756-1833 .- 0959-8138. ; 366
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To investigate the cardiovascular effectiveness of sodium glucose cotransporter 2 (SGLT2) inhibitors in routine clinical practice. Cohort study using data from nationwide registers and an active-comparator new-user design. 20 983 new users of SGLT2 inhibitors and 20 983 new users of dipeptidyl peptidase 4 (DPP4) inhibitors, aged 35-84, matched by age, sex, history of major cardiovascular disease, and propensity score. Primary outcomes were major cardiovascular events (composite of myocardial infarction, stroke, and cardiovascular death) and heart failure (hospital admission for heart failure or death due to heart failure). Secondary outcomes were the individual components of the cardiovascular composite and any cause death. In the primary analyses, patients were defined as exposed from treatment start throughout follow-up (analogous to intention to treat); additional analyses were conducted with an as-treated exposure definition. Cox regression was used to estimate hazard ratios. Mean age of the study cohort was 61 years, 60% were men, and 19% had a history of major cardiovascular disease. Of the total 27 416 person years of follow-up in the SGLT2 inhibitor group, 22 627 (83%) was among patients who initiated dapagliflozin, 4521 (16%) among those who initiated empagliflozin, and 268 (1%) among those who initiated canagliflozin. During follow-up, 467 SGLT2 inhibitor users (incidence rate 17.0 events per 1000 person years) and 662 DPP4 inhibitor users (18.0) had a major cardiovascular event, whereas 130 (4.7) and 265 (7.1) had a heart failure event, respectively. Hazard ratios were 0.94 (95% confidence interval 0.84 to 1.06) for major cardiovascular events and 0.66 (0.53 to 0.81) for heart failure. Hazard ratios were consistent among subgroups of patients with and without history of major cardiovascular disease and with and without history of heart failure. Hazard ratios for secondary outcomes, comparing SGLT2 inhibitors with DPP4 inhibitors, were 0.99 (0.85 to 1.17) for myocardial infarction, 0.94 (0.77 to 1.15) for stroke, 0.84 (0.65 to 1.08) for cardiovascular death, and 0.80 (0.69 to 0.92) for any cause death. In the as-treated analyses, hazard ratios were 0.84 (0.72 to 0.98) for major cardiovascular events, 0.55 (0.42 to 0.73) for heart failure, 0.93 (0.76 to 1.14) for myocardial infarction, 0.83 (0.64 to 1.07) for stroke, 0.67 (0.49 to 0.93) for cardiovascular death, and 0.75 (0.61 to 0.91) for any cause death. In this large Scandinavian cohort, SGLT2 inhibitor use compared with DPP4 inhibitor use was associated with reduced risk of heart failure and any cause death, but not with major cardiovascular events in the primary intention-to-treat analysis. In the additional as-treated analyses, the magnitude of the association with heart failure and any cause death became larger, and a reduced risk of major cardiovascular events that was largely driven by the cardiovascular death component was observed. These data help inform patients, practitioners, and authorities regarding the cardiovascular effectiveness of SGLT2 inhibitors in routine clinical practice.
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| 6. |
- Steineck, I., et al.
(författare)
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Insulin pump therapy, multiple daily injections, and cardiovascular mortality in 18 168 people with type 1 diabetes: observational study
- 2015
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Ingår i: Bmj-British Medical Journal. - : BMJ. - 1756-1833. ; 350
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To investigate the long term effects of continuous subcutaneous insulin infusion (insulin pump therapy) on cardiovascular diseases and mortality in people with type 1 diabetes. Design Observational study. 18 168 people with type 1 diabetes, 2441 using insulin pump therapy and 15 727 using multiple daily insulin injections. Cox regression analysis was used to estimate hazard ratios for the outcomes, with stratification of propensity scores including clinical characteristics, risk factors for cardiovascular disease, treatments, and previous diseases. Follow-up was for a mean of 6.8 years until December 2012, with 114 135 person years. With multiple daily injections as reference, the adjusted hazard ratios for insulin pump treatment were significantly lower: 0.55 (95% confidence interval 0.36 to 0.83) for fatal coronary heart disease, 0.58 (0.40 to 0.85) for fatal cardiovascular disease (coronary heart disease or stroke), and 0.73 (0.58 to 0.92) for all cause mortality. Hazard ratios were lower, but not significantly so, for fatal or non-fatal coronary heart disease and fatal or non-fatal cardiovascular disease. Unadjusted absolute differences were 3.0 events of fatal coronary heart disease per 1000 person years; corresponding figures were 3.3 for fatal cardiovascular disease and 5.7 for all cause mortality. When lower body mass index and previous cardiovascular diseases were excluded, results of subgroup analyses were similar to the results from complete data. A sensitivity analysis of unmeasured confounders in all individuals showed that an unmeasured confounders with hazard ratio of 1.3 would have to be present in > 80% of the individuals treated with multiple daily injections versus not presence in those treated with pump therapy to invalidate the significantly lower hazard ratios for fatal cardiovascular disease. Data on patient education and frequency of blood glucose monitoring were missing, which might have influenced the observed association. Among people with type 1 diabetes use of insulin pump therapy is associated with lower cardiovascular mortality than treatment with multiple daily insulin injections.
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| 7. |
- Ueda, P., et al.
(författare)
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Sodium glucose cotransporter 2 inhibitors and risk of serious adverse events: nationwide register based cohort study
- 2018
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Ingår i: BMJ (Clinical research ed.). - : BMJ. - 1756-1833 .- 0959-8138. ; 363
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To assess the association between the use of sodium glucose cotransporter 2 (SGLT2) inhibitors and seven serious adverse events of current concern. DESIGN: Register based cohort study. SETTING: Sweden and Denmark from July 2013 to December 2016. PARTICIPANTS: A propensity score matched cohort of 17213 new users of SGLT2 inhibitors (dapagliflozin, 61%; empagliflozin, 38%; canagliflozin, 1%) and 17213 new users of the active comparator, glucagon-like peptide 1 (GLP1) receptor agonists. MAIN OUTCOME MEASURES: The primary outcomes were lower limb amputation, bone fracture, diabetic ketoacidosis, acute kidney injury, serious urinary tract infection, venous thromboembolism, and acute pancreatitis, as identified from hospital records. Hazard ratios and 95% confidence intervals were estimated by using Cox proportional hazards models. RESULTS: Use of SGLT2 inhibitors, as compared with GLP1 receptor agonists, was associated with an increased risk of lower limb amputation (incidence rate 2.7 v 1.1 events per 1000 person years, hazard ratio 2.32, 95% confidence interval 1.37 to 3.91) and diabetic ketoacidosis (1.3 v 0.6, 2.14, 1.01 to 4.52) but not with bone fracture (15.4 v 13.9, 1.11, 0.93 to 1.33), acute kidney injury (2.3 v 3.2, 0.69, 0.45 to 1.05), serious urinary tract infection (5.4 v 6.0, 0.89, 0.67 to 1.19), venous thromboembolism (4.2 v 4.1, 0.99, 0.71 to 1.38) or acute pancreatitis (1.3 v 1.2, 1.16, 0.64 to 2.12). CONCLUSIONS: In this analysis of nationwide registers from two countries, use of SGLT2 inhibitors, as compared with GLP1 receptor agonists, was associated with an increased risk of lower limb amputation and diabetic ketoacidosis, but not with other serious adverse events of current concern. 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.
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