Study design and baseline profile for adults with type 2 diabetes in the once-weekly subcutaneous SEmaglutide randomized PRAgmatic (SEPRA) trial.

INTRODUCTION: Once-weekly subcutaneous semaglutide, a glucagon-like peptide-1 analog, is approved in the USA as an adjunct to diet and exercise for adults with inadequately controlled type 2 diabetes (T2D) to improve glycemic control and reduce the risk of major adverse cardiovascular events in people with T2D and established cardiovascular disease. The Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes (SUSTAIN) phase III clinical trial program demonstrated the efficacy and safety of once-weekly subcutaneous semaglutide; however, determining its effectiveness in a real-world setting could support decision-making by clinicians, payers and policy makers in routine clinical practice. RESEARCH DESIGN AND METHODS: SEmaglutide PRAgmatic (SEPRA) is an ongoing open-label, randomized, pragmatic clinical trial designed to compare the effects of once-weekly subcutaneous semaglutide versus standard of care in US health-insured adults with T2D and physician-determined inadequate glycemic control. The primary end point is the proportion of participants achieving glycated hemoglobin (HbA1c) <7.0% at year 1; other key outcomes include glycemic control, weight loss, healthcare utilization, and patient-reported outcomes. Individual-level data will be collected from routine clinical practice and health insurance claims. The last patient last visit is expected by June 2023. RESULTS: Between July 2018 and March 2021, 1278 participants were enrolled from 138 study sites across the USA. At baseline, 54% were male with mean±SD age 57.4±11.1 years and body mass index 35.7±8.0 kg/m2. Mean diabetes duration was 7.4±6.0 years and mean HbA1c was 8.5±1.6%. At baseline, concomitant antidiabetes medications included metformin, sulfonylureas, sodium-glucose co-transporter-2 inhibitors, and dipeptidyl peptidase-4 inhibitors. The majority of participants had hypertension and dyslipidemia. The trial design was self-assessed using the PRagmatic Explanatory Continuum Indicator Summary-2 tool by the study steering group and was scored 4-5 in all domains suggesting a highly pragmatic study. CONCLUSIONS: SEPRA, a highly pragmatic ongoing study, will provide data on the effects of once-weekly subcutaneous semaglutide in a real-world setting when used during routine management of T2D. TRIAL REGISTRATION NUMBER: NCT03596450.

Health care resource utilization and cost for asthma patients regularly treated with oral corticosteroids - a Swedish observational cohort study (PACEHR).

BACKGROUND: Patients with severe uncontrolled asthma may receive oral corticosteroid (OCS) treatment regularly. The present study investigated the health care resource utilization and cost in regularly OCS treated Swedish asthma patients. METHODS: Primary care medical records data were linked to data from Swedish national health registries. Patients ≥18 years with a drug claim for obstructive pulmonary diseases during 2007-2009 (index date) and a prior asthma diagnosis, were classified by their OCS claims during the 12-months' post index period: regular OCS equals ≥5 mg per day; periodic OCS less than 5 mg per day; or non-OCS users. Cost of asthma- and OCS-morbidity-related health care resource utilization were calculated. RESULTS: A total of 15,437 asthma patients (mean age 47.8, female 62.6%), whereof 223 (1.44%) were regular OCS users, 3054 (19.7%) were periodic, and 12,160 (78.7%) were non-OCS users. Regular OCS users were older and more often females, had lower lung function, greater eosinophil count and more co-morbidities at baseline compared with the other groups. Age-adjusted annual total health care cost was three-times greater in the regular OCS group (€5615) compared with the non-OCS users (€1980) and twice as high as in the periodic OCS group (€2948). The major cost driver in the non-OCS and periodic OCS groups were primary care consultations, whereas inpatient costs were the major cost driver in the regular OCS group. The asthma related costs represented 10-12% of the total cost in all three groups. CONCLUSION: In this real-life asthma study in Sweden, the total yearly cost of health care resource utilization for a regular OCS user was three times greater than for a patient with no OCS use, indicating substantial economic and health care burden for asthma patients on regular oral steroid treatment.

Coronary artery disease severity and long-term cardiovascular risk in patients with myocardial infarction: a Danish nationwide register-based cohort study.

Aim: Long-term prognostic impact of coronary artery disease (CAD) severity in stable post-myocardial infarction (MI) patients is not well known. We examined the impact of CAD severity and co-morbidity on the long-term (1 year and beyond) risk of cardiovascular events post-MI. Methods and results: From nationwide administrative and clinical registers, we identified 55 747 MI patients, during 2004-2010, who had not experienced subsequent MI, stroke, or death within 7 days post-discharge. The risk for primary composite endpoint (MI, stroke, or cardiovascular death) was estimated for the first 365 days after MI (index MI) and from day 366 to study completion (stable post-MI population), corresponding to a mean follow-up of 3.6 (2.2) years. Risk was assessed using cumulative incidence, multivariable adjusted logistic regression and Cox proportional-hazards models. The 1-year cumulative incidence for primary endpoint was 20.0% [95% confidence interval (CI), (19.6-20.3)]. Correspondingly, the 4-year cumulative incidence for primary endpoint was 21.0% (95% CI, 20.6-21.4) in patients without events on the first year. In multivariable models with no significant stenosis as reference, CAD severity was the most important risk factor for cardiovascular events the first 365 days [left main stenosis (LMS): odds ratio and 95% CI, 4.37, 3.69-5.17; 3-vessel disease (VD), 4.18, 3.66-4.77; 2-VD, 3.23, 2.81-3.72; 1-VD, 2.12,-1.85-2.43] and remained from day 366 to study completion [LMS: hazard ratio and 95% CI, 1.91, 1.64-2.22; 3-VD, 1.85,1.65-2.07; 2-VD, 1.55, 1.38-1.74; 1-VD, 1.30, 1.16-1.45]. Conclusion: Despite contemporary treatment at baseline, stable post-MI patients' 4-year outcome was similar to 1-year outcome after MI, and CAD severity remained a critical risk factor the first year and thereafter.