Emulation of the SOUL Diabetes Trial in Healthcare Claims

Prior treatment

• Any of the following: myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischemic attack within the past 60 days prior to the day of screening
• Treatment with any glucagon-like peptide-1 receptor agonist within 30 days before screening

Other illness

• Heart failure presently classified as being in New York Heart Association Class IV
• History of MEN-2 or family history of medullary thyroid cancer
• History of pancreatitis
• History of or planning bariatric surgery, including banding procedures or surgical gastric and/or intestinal bypass
• History of cancer, other than non-melanoma skin cancer, that required therapy in the 5 years prior to randomization
• History of diabetic ketoacidosis

Lab values

• Chronic or intermittent hemodialysis or peritoneal dialysis or severe renal impairment (corresponding to eGFR \<30 ml/min/1.73 m2)

Age

• Missing age or gender

Other

• Semaglutide
• Plans for pregnancy during the course of the study for women of child-bearing potential
• Proliferative retinopathy or maculopathy requiring acute treatment
• Nursing home admission

• Type 2 diabetes mellitus
• Male or female, age equal to or above 50 years
  • At least one of the following conditions:
• Coronary heart disease defined by at least one of the following criteria:
  • Prior myocardial infarction ii. Prior coronary revascularization procedure ii. 50% or above stenosis in coronary artery documented by cardiac catheterization, computerized tomography coronary angiography iv. Coronary heart disease with ischemia documented by stress test with any imaging modality
• Cerebrovascular disease defined by at least one of the following criteria:
  • Prior stroke ii. Prior carotid artery revascularization procedure iii. 50% or above stenosis in carotid artery documented by x-ray angiography, magnetic resonance angiography, computerized tomography angiography or Doppler ultrasound
• Symptomatic peripheral artery disease (PAD) defined by at least one of the following criteria:
  • Intermittent claudication with an Ankle-brachial index (ABI) below 0.85 at rest ii. Intermittent claudication with a 50% or above stenosis in peripheral artery (excluding carotid) documented by x-ray angiography, magnetic resonance angiography, computerized tomography angiography or Doppler ultrasound iii. Prior peripheral artery(excluding carotid) revascularization procedure iv. Lower extremity amputation at or above ankle due to atherosclerotic disease (excluding trauma or osteomyelitis)
• Chronic kidney disease defined as: i. eGFR below 60mL/min/1.73 m\^2 (based on medical records using latest available and no more than 6 months old assessment)

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