In our registry-based observational study, patients with type 1 diabetes and a glycated hemoglobin level of 6.9% or lower had a risk of death from any cause or from cardiovascular causes that was twice as high as the risk for matched controls. (Funded by the Swedish Society of Medicine and others.).

Mortality among persons with type 2 diabetes, as compared with that in the general population, varied greatly, from substantial excess risks in large patient groups to lower risks of death depending on age, glycemic control, and renal complications. (Funded by the Swedish government and others.).

Swedish Heart and Lung Foundation.

ObjectiveTo assess the association between the use of sodium glucose cotransporter 2 (SGLT2) inhibitors and seven serious adverse events of current concern.DesignRegister based cohort study.SettingSweden and Denmark from July 2013 to December 2016.ParticipantsA propensity score matched cohort of 17 213 new users of SGLT2 inhibitors (dapagliflozin, 61%; empagliflozin, 38%; canagliflozin, 1%) and 17 213 new users of the active comparator, glucagon-like peptide 1 (GLP1) receptor agonists.Main outcome measuresThe 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.ResultsUse 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).ConclusionsIn 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.

No abstract

ObjectiveTo 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.DesignObservational study between July 2004 and December 2010, mean follow-up 3.9 years.SettingHospital outpatient clinics and primary care in Sweden.Participants51 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 measuresRisks 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.ResultsCompared 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.ConclusionsMetformin 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.

S. (2018) Excess mortality and cardiovascular disease in young adults with type 1 diabetes in relation to age at onset: a nationwide, registerbased cohort study. Lancet, 392(10146), pp. 477-486. There may be differences between this version and the published version. You are advised to consult the publisher's version if you wish to cite from it. Abstract word count: 258 words 26Evidence before this study 27 People with type 1 diabetes are at 2-to 5-fold increased risk of death and 3-to 7-fold increased risk 28 of coronary heart disease. Several risk factors, notably glycemic control, affect survival in type 1 29 diabetes. The importance of age at disease onset, however, remains weakly studied. Guidelines do 30 not articulate any specific recommendations in relation to age at disease onset, only duration. We 31 did a systematic search in PubMed for articles published between Jan 1, 1960, and April 15, 2018. 32Our search terms included "type 1 diabetes", "age at diagnosis", "age at disease onset", "childhood 33 onset", "late onset", "debut age", "mortality", "cardiovascular disease", "coronary artery disease", 34 "myocardial infarction". We searched articles by title and abstract to identify relevant studies. 35Studies were also sought within reference lists of eligible studies. We considered studies that 36 evaluated association between age at onset/diagnosis of type 1 diabetes and cardiovascular disease 37 and survival. Studies using diabetes free controls as comparator were of primary interest, as such 38 studies addresses the excess risk conferred by diabetes. 40Added value of this study 41 By studying 27,195 individuals with type 1 diabetes and 135,178 matched controls, we demonstrate 42 a ubiquitous inverse association between age at diagnosis and risk of mortality and cardiovascular 43 disease, independent of diabetes duration. Patients with type 1 diabetes with disease onset before 44 10 years of age experienced a 30-fold increased risk of CHD and AMI. Women with onset of type 1 45 diabetes before 10 years of age displayed a 60-and 90-fold increased risk of CHD and AMI, 46 respectively. The difference in risk levels between those with onset at age 0-10 years and 25-30 47 years was up to 5-fold (AMI and CHD). Although absolute risks were low in this young cohort, 48 developing T1D before 10 years of age resulted in a loss of 17.7 and 14.2 life years for women and 49 men, respectively, whereas years of life lost were around 9-10 years with later age at diagnosis. 51Implications of all the available evidence 52 Age at disease onset appears an important determinant of survival and, in particular of, 53 cardiovascular disease in type 1 diabetes. These findings suggest that more patients with earlier 54 onset type 1 diabetes be offered cardioprotective medications (statins, BP medications) sooner than 55 currently practiced. A greater effort towards improved glycaemia control in such individual would 56 also be beneficial. Abstract 61 Background 62We compared individuals with type 1 diabetes (T1D) to match...

Objective To investigate the cardiovascular effectiveness of sodium glucose cotransporter 2 (SGLT2) inhibitors in routine clinical practice. Design Cohort study using data from nationwide registers and an active-comparator new-user design. Setting Denmark, Norway, and Sweden, from April 2013 to December 2016. Participants 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. Main outcome measures 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. Results 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. Conclusions 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.