Emulation of the SUSTAIN6 Diabetes Trial Using Healthcare Claims

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 Inclusion Criteria: * 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 Exclusion Criteria: * Type 1 diabetes mellitus, secondary or gestational diabetes * 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 * History of chronic pancreatitis or idiopathic acute pancreatitis * Acute coronary or cerebro-vascular event within 90 days prior to randomization * 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 * Chronic hemodialysis or peritoneal dialysis * End stage liver disease * A prior solid organ transplant or awaiting solid organ transplant * Diagnosis of malignant neoplasm in the previous 5 years * Female of childbearing potential who is pregnant, breast-feeding or intends to become pregnant or is not using an adequate contraceptive method * Known use of non-prescribed narcotics or illicit drugs * Proliferative retinopathy or maculopathy requiring treatment * Missing age or gender * Nursing home admission