The burden of poor glycaemic control in people with newly diagnosed type 2 diabetes in Sweden: A health economic modelling analysis based on nationwide data.

AIM: To evaluate the economic and clinical burden associated with poor glycaemic control in Sweden, in people with type 2 diabetes (T2D) initiating first-line glucose-lowering therapy. MATERIALS AND METHODS: Population data were obtained from Swedish national registers. Immediate glycaemic control was compared with delays in achieving control of 1 and 3 years, with outcomes projected over 3, 10 and 50 years in the validated IQVIA CORE Diabetes Model. Glycaemic control was defined as glycated haemoglobin (HbA1c) targets of 52, 48 and 42 mmol/mol, as recommended in Swedish guidelines, according to age and disease duration. Costs (expressed in 2019 Swedish krona [SEK]) were accounted from a Swedish societal perspective. RESULTS: Immediate glycaemic control was associated with population-level cost savings of up to SEK 279 million and SEK 673 million versus delays of 1 and 3 years, respectively, as well as small population-level life expectancy benefits of up to 1305 and 2590 life years gained. Reduced levels of burden were a result of lower incidence and delayed time to onset of diabetes-related complications. CONCLUSIONS: Even in people with T2D initiating first-line glucose-lowering therapy, the economic burden of poor glycaemic control in Sweden is substantial, but could be reduced by early and effective treatment to achieve glycaemic targets.

Impact of variable look-back periods on the incidence rates of chronic diseases using real world data.

PURPOSE: Estimating disease incidence based on secondary data requires a look-back period to exclude patients with pre-existing disease from the incidence risk set. However, the optimal length of the look-back period and its impact on incidence rates are often unknown. We studied the impact of the length of the look-back period on incidence rates of 24 different chronic diseases. METHODS: Everyone residing in Sweden between January 1, 2005 and December 31, 2013 were identified from national registries and followed up to 2 years (through December 31, 2015). Outcome events were identified from inpatient and outpatient hospital contacts and incidence rates were calculated per 100 000 person-years. The length of the look-back period was varied with 6-month increments, starting at 6 months. The maximum look-back period of 9 years was used as reference period. RESULTS: There were 7 943 807 individuals with a look-back period of at least 9 years (mean age 46.5 years) and a mean follow-up time of 1.97 years. Incidence rates were higher across all diseases when restricting the look-back to 1 year compared to 9 years, with a magnitude of overestimation of the incidence rates between 13% (temporal arteritis) and 174% (type 1 diabetes). However, for most diseases the effect of extending the look-back period beyond 3-5 years appeared comparably small. CONCLUSIONS: This study illustrates how short look-back periods cause overestimation of the incidence rates of chronic diseases, suggesting that sensitivity analyses with respect to look-back period are considered, particularly using data sources with limited information on past medical history.

Cancer risk among insulin users: comparing analogues with human insulin in the CARING five-country cohort study.

AIMS/HYPOTHESIS: The aim of this work was to investigate the relationship between use of certain insulins and risk for cancer, when addressing the limitations and biases involved in previous studies. METHODS: National Health Registries from Denmark (1996-2010), Finland (1996-2011), Norway (2005-2010) and Sweden (2007-2012) and the UK Clinical Practice Research Datalink database (1987-2013) were used to conduct a cohort study on new insulin users (N = 327,112). By using a common data model and semi-aggregate approach, we pooled individual-level records from five cohorts and applied Poisson regression models. For each of ten cancer sites studied, we estimated the rate ratios (RRs) by duration (≤0.5, 0.5-1, 1-2, 2-3, 3-4, 4-5, 5-6 and >6 years) of cumulative exposure to insulin glargine or insulin detemir relative to that of human insulin. RESULTS: A total of 21,390 cancer cases occurred during a mean follow-up of 4.6 years. No trend with cumulative treatment time for insulin glargine relative to human insulin was observed in risk for any of the ten studied cancer types. Of the 136 associations tested in the main analysis, only a few increased and decreased risks were found: among women, a higher risk was observed for colorectal (RR 1.54, 95% CI 1.06, 2.25) and endometrial cancer (RR 1.78, 95% CI 1.07, 2.94) for ≤0.5 years of treatment and for malignant melanoma for 2-3 years (RR 1.92, 95% CI 1.02, 3.61) and 4-5 years (RR 3.55, 95% CI 1.68, 7.47]); among men, a lower risk was observed for pancreatic cancer for 2-3 years (RR 0.34, 95% CI 0.17, 0.66) and for liver cancer for 3-4 years (RR 0.36, 95% CI 0.14, 0.94) and >6 years (RR 0.22, 95% CI 0.05, 0.92). Comparisons of insulin detemir with human insulin also showed no consistent differences. CONCLUSIONS/INTERPRETATION: The present multi-country study found no evidence of consistent differences in risk for ten cancers for insulin glargine or insulin detemir use compared with human insulin, at follow-up exceeding 5 years.

Cardiovascular safety of glucose-lowering agents as add-on medication to metformin treatment in type 2 diabetes: report from the Swedish National Diabetes Register.

AIM: To investigate the relative safety of various glucose-lowering agents as add-on medication to metformin in type 2 diabetes in an observational study linking five national health registers. RESEARCH DESIGN AND METHODS: Patients with type 2 diabetes who had been on metformin monotherapy and started another agent in addition to metformin were eligible for inclusion. The study period was 2005-2012. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of mortality, cardiovascular disease (CVD), coronary heart disease (CHD), stroke and congestive heart failure (CHF) were estimated using Cox proportional hazards models, weighted for a propensity score. RESULTS: Of the 20 422 patients included in the study, 43% started on second-line treatment with sulphonylurea (SU), 21% basal insulin, 12% thiazolidinedione (TZD), 11% meglitinide, 10% dipeptidyl peptidase-4 (DPP-4) inhibitor, 1% glucagon-like peptide-1 (GLP-1) receptor agonist and 1% acarbose. At the index date, the mean patient age was ~60 years for all groups except the GLP-1 receptor agonist (56.0 years) and SU (62.9 years) groups. Diabetes duration and glycated haemoglobin levels were similar in all groups. When compared with SU, basal insulin was associated with an 18% higher risk and TZD with a 24% lower risk of mortality [HR 1.18 (95% CI 1.03-1.36) and 0.76 (95% CI 0.62-0.94)], respectively. DPP-4 inhibitor treatment was associated with significantly lower risks of CVD, fatal CVD, CHD, fatal CHD and CHF. CONCLUSIONS: This nationwide observational study showed that second-line treatment with TZD and DPP-4 inhibitor as add-on medication to metformin were associated with significantly lower risks of mortality and cardiovascular events compared with SU, whereas basal insulin was associated with a higher risk of mortality.

Durability of oral hypoglycemic agents in drug naïve patients with type 2 diabetes: report from the Swedish National Diabetes Register (NDR).

OBJECTIVE: To analyze the durability of monotherapy with different classes of oral hypoglycemic agents (OHAs) in drug naïve patients with type 2 diabetes mellitus (T2DM) in real life. METHODS: Men and women with T2DM, who were new users of OHA monotherapy and registered in the Swedish National Diabetes Register July 2005-December 2011, were available (n=17 309) and followed for up to 5.5 years. Time to monotherapy failure, defined as discontinuation of continuous use with the initial agent, switch to a new agent, or add-on treatment of a second agent, was analyzed as a measure of durability. Baseline characteristics were balanced by propensity score matching 1:5 between groups of sulfonylurea (SU) versus metformin (n=4303) and meglitinide versus metformin (n=1308). HRs with 95% CIs were calculated using Cox regression models. RESULTS: SU and meglitinide, as compared with metformin, were associated with increased risk of monotherapy failure (HR 1.74; 95% CI 1.56 to 1.94 and 1.66; 1.37 to 2.00 for SU and meglitinide, respectively). When broken down by type of monotherapy failure, SU and meglitinide were associated with an increased risk of add-on treatment of a second agent (HR 3.14; 95% CI 2.66 to 3.69 and 2.52; 1.89 to 3.37 for SU and meglitinide, respectively) and of switch to a new agent (HR 2.81; 95% CI 2.01 to 3.92 and 3.78; 2.25 to 6.32 for SU and meglitinide, respectively). The risk of discontinuation did not differ significantly between the groups. CONCLUSIONS: In this nationwide observational study reflecting clinical practice, SU and meglitinide showed substantially increased risk of switch to a new agent or add on of a second agent compared with metformin. These results indicate superior glycemic durability with metformin compared with SU and also meglitinide in real life.

Metabolic effects of Basal or premixed insulin treatment in 5077 insulin-naïve type 2 diabetes patients: registry-based observational study in clinical practice.

INTRODUCTION: To investigate the clinical effects associated with premixed insulin (PM) and basal insulin [insulin NPH (NPH), insulin glargine (IG), insulin detemir (ID)], in insulin-naïve patients with type 2 diabetes in routine clinical care. MATERIALS AND METHODS: Cohort study based on data from the Swedish National Diabetes Register, including 5,077 patients, resident in the Western region of Sweden. Patients were included between 1 July 2006 and 31 December 2009 and followed for 12 months. Changes in HbA1c, body mass index (BMI) and required insulin doses were compared between the different insulin types. Covariance adjustments were performed to adjust for differences between the groups. RESULTS: NPH, IG, ID and PM were all associated with significant reductions in HbA1c, mean ± standard deviation ranged between 6.6 ± 17.4 mmol/mol (IG) and 8.9 ± 17.7 mmol/mol (NPH), during the 12 months of follow-up. There were no statistically significant differences in the magnitude of HbA1c reduction between the insulin types. PM required 59% higher and ID 25% higher insulin doses to achieve a similar HbA1c reduction as NPH. PM was associated with a significantly greater increase in BMI compared with NPH (p = 0.016), while IG and ID did not differ significantly from NPH. The number of patients experiencing severe hypoglycemia was low, but highest in patients treated with PM (p = 0.023). CONCLUSIONS: NPH, IG, ID and PM were found to be equally effective in lowering HbA1c in insulin-naïve patients with type 2 diabetes in routine clinical care in Sweden. The effects on weight, dose and treatment persistence support the recommendation of NPH or IG as first and second choices in this group of patients requiring initiation of insulin treatment.

Aspirin treatment and risk of first incident cardiovascular diseases in patients with type 2 diabetes: an observational study from the Swedish National Diabetes Register.

OBJECTIVES: To investigate the benefits and risks associated with aspirin treatment in patients with type 2 diabetes and no previous cardiovascular disease (CVD) in clinical practice. DESIGN: Population-based cohort study between 2005 and 2009, mean follow-up 3.9 years. SETTING: Hospital outpatient clinics and primary care in Sweden. PARTICIPANTS: Men and women with type 2 diabetes, free from CVD, including atrial fibrillation and congestive heart failure, at baseline, registered in the Swedish National Diabetes Register, with continuous low-dose aspirin treatment (n=4608) or no aspirin treatment (n=14 038). MAIN OUTCOME MEASURES: Risks of CVD, coronary heart disease (CHD), stroke, mortality and bleedings, associated with aspirin compared with no aspirin, were analysed in all patients and in subgroups by gender and estimated cardiovascular risk. Propensity scores were used to adjust for several baseline risk factors and characteristics at Cox regression, and the effect of unknown covariates was evaluated in a sensitivity analysis. RESULTS: There was no association between aspirin use and beneficial effects on risks of CVD or death. Rather, there was an increased risk of non-fatal/fatal CHD associated with aspirin; HR 1.19 (95% CI 1.01 to 1.41), p=0.04. The increased risk of cardiovascular outcomes associated with aspirin was seen when analysing women separately; HR 1.41 (95% CI 1.07 to 1.87), p=0.02, and HR 1.28 (95% CI 1.01 to 1.61), p=0.04, for CHD and CVD, respectively, but not for men separately. There was a trend towards increased risk of a composite of bleedings associated with aspirin, n=157; HR 1.41 (95% CI 0.99 to 1.99). CONCLUSIONS: The results support the trend towards more restrictive use of aspirin in patients with type 2 diabetes and no previous CVD. More research is needed to explore the differences in aspirin's effects in women and men.

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.

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.