Emulation of the SUSTAIN6 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
• Treatment with insulin other than basal and pre-mixed insulin within 90 days prior to screening - except for short-term use in connection with intercurrent illness
• Acute decompensation of glycaemic control requiring immediate intensification of treatment to prevent acute complications of diabetes (eg diabetes ketoacidosis) within 90 days prior to screening
• Acute coronary or cerebro-vascular event within 90 days prior to randomization
• A prior solid organ transplant or awaiting solid organ transplant
• Diagnosis of malignant neoplasm in the previous 5 years
• Known use of non-prescribed narcotics or illicit drugs

Other illness

• Type 1 diabetes mellitus, secondary or gestational diabetes
• History of 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
• Personal history of non-familial medullary thyroid carcinoma
• End stage liver disease

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
• Anti-diabetic drug naïve, or treated with one or two oral antidiabetic drug (OADs), or treated with human Neutral Protamin Hagedorn (NPH) insulin or long-acting insulin analogue or pre-mixed insulin, both types of insulin either alone or in combination with one or two OADs
• 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 injectable semaglutide in the US began on 5th December 2017.
• Optum: Study period between 5th Dec 2017 - 29th February 2024 Marketscan: Study period between 5th Dec 2017 - 31st Dec 2022 Medicare: Study period between 5th Dec 2017 - 31st Dec 2020