Emulation of the SUSTAIN6 Diabetes Trial Using Healthcare Claims

NCT06659744 | Completed FDA Drug

• 1 other identifier: 2018P002966-DUP-SUSTAIN
• Study Type: observational
• Target: 158,310
• Locations: 1 country
• Sites: 1

Brief Summary

Investigators are building an empirical evidence base for real world data through large-scale emulation of randomized controlled trials. The investigators' goal is to understand for what types of clinical questions real world data analyses can be conducted with confidence and how to implement such studies.

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (1)

• Major adverse cardiac event (MACE), including myocardial infarction, stroke, and all cause death

  Hazard ratio

  Through study completion (1 day after cohort entry date until the first of outcome or censoring)

Other Outcomes (1)

• Cataract surgery (negative control)

  Through study completion (1 day after cohort entry date until the first of outcome or censoring)

Study Arms (2)

New use of semaglutide injection

Exposure group

Drug: New use of semaglutide injection

New initiation of sitagliptin

Reference group

Drug: New initiation of sitagliptin

Interventions

New use of semaglutide injection DRUG

New use of semaglutide injection dispensing claim is used as the exposure.

New use of semaglutide injection

New initiation of sitagliptin DRUG

New initiation of sitagliptin dispensing claim is used as the reference.

New initiation of sitagliptin

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population included patients with Type 2 Diabetes (Type2DM) who had not been treated with antihyperglycemic agents or had been treated with no more than two oral antihyperglycemic agents, with or without NPH or long-acting insulin, \>=50 years with established cardiovascular disease OR \>=60 years with subclinical cardiovascular disease.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Brigham and Women's Hospital: lead

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02120, United States

Location

Related Publications (1)

• Kruger N, Schneeweiss S, Desai RJ, Sreedhara SK, Kehoe AR, Fuse K, Hahn G, Schunkert H, Wang SV. Cardiovascular outcomes of semaglutide and tirzepatide for patients with type 2 diabetes in clinical practice. Nat Med. 2025 Nov 9. doi: 10.1038/s41591-025-04102-x. Online ahead of print.

  PMID: 41207920 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Shirley Wang, PhD, ScM

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: October 24, 2024
• First Posted: October 26, 2024
• Study Start: October 24, 2024
• Primary Completion: March 6, 2025
• Study Completion: March 6, 2025
• Last Updated: October 15, 2025

Record last verified: 2025-08

Locations

US (1)