Glucagon-like peptide-1 receptor agonists and risk of major adverse liver outcomes in patients with chronic liver disease and type 2 diabetes.

OBJECTIVE: Phase II trials suggest glucagon-like peptide-1 receptor (GLP1) agonists resolve metabolic dysfunction-associated steatohepatitis but do not affect fibrosis regression. We aimed to determine the long-term causal effect of GLP1 agonists on the risk of major adverse liver outcomes (MALO) in patients with any chronic liver disease and type 2 diabetes. DESIGN: We used observational data from Swedish healthcare registers 2010-2020 to emulate a target trial of GLP1 agonists in eligible patients with chronic liver disease and type 2 diabetes. We used an inverse-probability weighted marginal structural model to compare parametric estimates of 10-year MALO risk (decompensated cirrhosis, hepatocellular carcinoma, liver transplantation or MALO-related death) in initiators of GLP1 agonists with non-initiators. We randomly sampled 5% of the non-initiators to increase computational efficiency. RESULTS: GLP1 agonist initiators had a 10-year risk of MALO at 13.3% (42/1026) vs 14.6% in non-initiators (1079/15 633) in intention-to-treat analysis (risk ratio (RR)=0.91, 95% CI=0.50 to 1.32). The corresponding 10-year per-protocol risk estimates were 7.4% (22/1026) and 14.4% (1079/15 633), respectively (RR=0.51, 95% CI=0.14 to 0.88). The per-protocol risk estimates at 6 years were 5.4% (21/1026) vs 9.0% (933/15 633) (RR=0.60, 95% CI=0.29 to 0.90) and at 8 years 7.2% (22/1026) vs 11.7% (1036/15 633) (RR=0.61, 95% CI=0.21 to 1.01). CONCLUSION: In patients with chronic liver disease and type 2 diabetes who adhered to therapy over time, GLP1 agonists may result in lower risk of MALO. This suggests that GLP1 agonists are promising agents to reduce risk of chronic liver disease progression in patients with concurrent type 2 diabetes, although this needs to be corroborated in randomised trials.

Economic burden of osteoarthritis - multi-country estimates of direct and indirect costs from the BISCUITS study.

Data from 'BISCUITS', a large Nordic cohort study linking several registries, were used to estimate differences in average direct and indirect costs between patients with osteoarthritis and controls (matched 1:1 based on birth year and sex) from the general population in Sweden, Norway, Finland and Denmark for 2017. Patients ≥18 years with ≥1 diagnosis of osteoarthritis (ICD-10: M15-M19) recorded in specialty or primary care (the latter available for a subset of patients in Sweden and for all patients in Finland) during 2011-2017 were included. Patients with a cancer diagnosis (ICD-10: C00-C43/C45-C97) were excluded. Productivity loss (sick leave and disability pension) and associated indirect costs were estimated among working-age adults (18-66 years). In 2017, average annual incremental direct costs among adults with osteoarthritis (n=1,157,236) in specialty care relative to controls ranged between €1,259 and €1,693 (p<0.001) per patient across all countries. Total average annual incremental costs were €3,224-€4,969 (p<0.001) per patient. Healthcare cost differences were mainly explained by osteoarthritis patients having more surgeries. However, among patients with both primary and secondary care data, primary care costs exceeded the costs of surgery. Primary care constituted 41 and 29 % of the difference in direct costs in Sweden and Finland, respectively. From a societal perspective, the total economic burden of osteoarthritis is substantial, and the incremental cost was estimated to €1.1-€1.3 billion yearly for patients in specialty care across the Nordic countries. When including patients in primary care, incremental costs rose to €3 billion in Sweden and €1.8 billion in Finland. Given the large economic impact, finding cost-effective and safe therapeutic strategies for these patients will be important.

Empagliflozin reduces cardiorenal events, healthcare resource use and mortality in Sweden compared to dipeptidyl peptidase-4 inhibitors: Real world evidence from the Nordic EMPRISE study.

AIMS: To evaluate effectiveness and healthcare resource utilization (HCRU) of empagliflozin versus dipeptidyl peptidase-4 inhibitors (DPP-4i) in Swedish clinical practice, as part of the EMPRISE EU study (EUPAS27606, NCT03817463). MATERIALS AND METHODS: A non-interventional, cohort study using retrospectively collected data from Swedish national registries. Adults with type 2 diabetes newly initiated on empagliflozin or DPP-4i from May 2014 to December 2018 were matched 1:1 using propensity scores based on >180 covariates. Cardiovascular outcomes included hospitalization for heart failure (HHF), all-cause mortality (ACM), myocardial infarction (MI), stroke and cardiovascular mortality (CVM), as well as their composite outcomes. Renal outcomes included end-stage renal disease (ESRD), estimated glomerular filtration rate (eGFR) decline to <60 ml/min/1.73 m2 and progression to micro/macroalbuminuria. HCRU outcomes were also assessed. Comparisons were done using Cox proportional hazards and Poisson regression models. RESULTS: Overall, 15,785 matched-pairs were identified, with a mean follow-up of 6.4 and 9.7 months for patients initiating empagliflozin versus DPP-4i, respectively. Empagliflozin was associated with significant reduction in rates of HHF (hazard ratio [HR] = 0.67; 95% confidence interval: 0.49-0.91), ACM (HR = 0.53; 0.41-0.68), HHF + ACM (HR = 0.59; 0.48-0.73), MI + stroke + ACM (HR = 0.68; 0.57-0.81), CVM (HR = 0.46; 0.29-0.73), HHF + CVM (HR = 0.61; 0.47-0.79) and MI + stroke + CVM (HR = 0.79; 0.63-0.98) versus DPP-4i. Empagliflozin also reduced the rates of ESRD (HR = 0.13; 0.03-0.57) and eGFR decline (HR = 0.83; 0.70-0.99). Regarding HCRU, empagliflozin was associated with lower risk of first inpatient stay (HR = 0.87; 0.81-0.93), and lower rate of inpatient and outpatient visits (rate ratio [RR] = 0.85; 0.80-0.89 and RR = 0.96; 0.94-0.98) than DPP-4i. CONCLUSIONS: Empagliflozin treatment compared to DPP-4i reduced cardiorenal events and overall mortality, which may explain lower HCRU among empagliflozin users in Sweden.

Burden of disease and management of osteoarthritis and chronic low back pain: healthcare utilization and sick leave in Sweden, Norway, Finland and Denmark (BISCUITS): study design and patient characteristics of a real world data study.

OBJECTIVES: Osteoarthritis (OA) and chronic low back pain (CLBP) are common musculoskeletal disorders with substantial patient and societal burden. Nordic administrative registers offer a unique opportunity to study the impact of these conditions in the real-world setting. The Burden of Disease and Management of Osteoarthritis and Chronic Low Back Pain: Health Care Utilization and Sick Leave in Sweden, Norway, Finland and Denmark (BISCUITS) study was designed to study disease prevalence and the societal and economic burden in broad OA and CLBP populations. METHODS: Patients in Sweden, Norway, Finland and Denmark with diagnoses of OA or CLBP (low back pain record plus ≥2 pain relief prescriptions to indicate chronicity) were identified in specialty care, in primary care (Sweden and Finland) and in a quality-of-care register (Sweden). Matched controls were identified for the specialty care cohort. Longitudinal data were extracted on prevalence, treatment patterns, patient-reported outcomes, social and economic burden. RESULTS: Almost 1.4 million patients with OA and 0.4 million with CLBP were identified in specialty care, corresponding to a prevalence in the Nordic countries of 6.3 and 1.9%, respectively. The prevalence increased to 11-14% for OA and almost 6% for CLBP when adding patients identified in primary care. OA patients had a higher Elixhauser comorbidity index (0.66 vs. 0.46) and were using opioids (44.7 vs. 10.2%) or long-term nonsteroidal anti-inflammatory drug (NSAIDs) (20.9 vs. 4.5%) more than four times as often as compared to controls. The differences were even larger for CLBP patients compared to their controls (comorbidity index 0.89 vs. 0.39, opioid use 77.7 vs. 9.4%, and long-term NSAID use 37.2 vs. 4.8%). CONCLUSIONS: The BISCUITS study offers an unprecedented, longitudinal healthcare data source to quantify the real-world burden of more than 1.8 million patients with OA or CLBP across four countries. In subsequent papers we aim to explore among others additional outcomes and subgroups of patients, primarily those patients who may benefit most from better healthcare management.

Real-World Costs of Continuous Insulin Pump Therapy and Multiple Daily Injections for Type 1 Diabetes: A Population-Based and Propensity-Matched Cohort From the Swedish National Diabetes Register.

OBJECTIVE: To investigate real-world costs of continuous insulin pump therapy compared with multiple daily injection (MDI) therapy for type 1 diabetes. RESEARCH DESIGN AND METHODS: Individuals with type 1 diabetes and pump therapy in the Swedish National Diabetes Register (NDR) since 2002 were eligible. Control subjects on MDI were matched 2:1 using time-varying propensity scores. Longitudinal data on health care resource use, antidiabetes treatment, sickness absence, and early retirement were taken from national registers for 2005-2013. Mean annual costs were analyzed using univariate analysis. Regression analyses explored the role of sociodemographic factors. Subgroup and sensitivity analyses were performed. RESULTS: A total of 14,238 individuals with type 1 diabetes entered in the NDR between 2005 and 2013 (insulin pump n = 4,991, MDI n = 9,247, with switches allowed during the study) were included. Mean age at baseline was 34 years, with 21 years of diabetes duration and a mean HbA1c of 8.1% (65 mmol/mol). We had 73,920 person-years of observation with a mean follow-up of 5 years per participant. Mean annual costs were higher for pump therapy than for MDI therapy ($12,928 vs. $9,005, respectively; P < 0.001; mean difference $3,923 [95% CI $3,703-$4,143]). Health care costs, including medications and disposables, accounted for 73% of the costs for pump therapy and 63% of the costs for MDI therapy. Regression analyses showed higher costs for low education, low disposable income, women, and older age. CONCLUSIONS: Nine years of real-world data on all measurable diabetes-related resource use show robust results for additional costs of insulin pump therapy in adults by subgroup and alternative propensity score specifications. Identification of tangible and intangible benefits of pump therapy over time remain important to support resource allocation decisions.