Emulating the PIONEER6 Diabetes Trial Using Healthcare Claims

Prior treatment

• Use of glucagon-like peptide-1 (GLP-1) receptor agonist (exenatide, liraglutide, or other) or pramlintide within 90 days prior to screening
• Use of any dipeptidyl peptidase 4 (DPP-IV) inhibitor within 30 days prior to screening
• Any of the following: myocardial infarction, stroke, or hospitalization for unstable angina or transient ischemic attack within the past 60 days prior to screening
• A prior solid organ transplant or awaiting solid organ transplant
• Diagnosis of malignant neoplasm in the previous 5 years

Other illness

• Type 1 diabetes mellitus, secondary or gestational diabetes
• History of diabetic ketoacidosis, chronic pancreatitis or idiopathic acute pancreatitis
• Chronic heart failure New York Heart Association (NYHA) class IV
• Personal or family history of multiple endocrine neoplasia type 2 (MEN2) or familial medullary thyroid carcinoma
• End stage liver disease
• History of major surgical procedures involving the stomach potentially affecting absorption of trial product (e.g., subtotal and total gastrectomy, sleeve gastrectomy, gastric bypass surgery)

Age

• Missing age or gender

Other

• Chronic hemodialysis or peritoneal dialysis
• Female of childbearing potential who is pregnant, breast-feeding or intends to become pregnant or is not using an adequate contraceptive method
• Proliferative retinopathy or maculopathy requiring treatment
• Nursing home admission

• Type 2 diabetes mellitus
• Age above or equal to 50 years at screening and clinical evidence of cardiovascular disease: prior myocardial infarction, prior stroke or prior transient ischemic attack, prior coronary, carotid or peripheral arterial revascularization, more than 50% stenosis on angiography or imaging of coronary, carotid or lower extremities arteries, chronic heart failure - New York Heart Association (NYHA) class II-III, chronic renal impairment documents by estimated eGFR \<60ml/min/1.73 m2 per MDRD
• Age 60 years or older with subclinical evidence of cardiovascular disease. Subclinical cardiovascular risk factors as one of the following: persistent microalbuminuria (30-299mg/g) or proteinuria, ankle/brachial index less than 0.9

Criteria the registry did not label

• Eligible cohort entry dates:
• Market availability of oral semaglutide in the US began on 19th September 2019.
• Optum: Study period between 20th Sept 2019 - 29th February 2024 Marketscan: Study period between 20th Sept 2019 - 31st Dec 2022 Medicare: Study period between 20th Sept 2019 - 31st Dec 2020