Observational analyses from ADVANCE and ADVANCE-ON.

Area of Science:

• Cardiovascular Medicine
• Endocrinology
• Epidemiology

Background:

• The Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation (ADVANCE) trial investigated interventions in high-risk diabetes patients.
• It employed a factorial design, comparing blood pressure lowering treatments against placebo and intensive glucose control against standard control.

Purpose of the Study:

• To document and explain the epidemiological work conducted alongside the ADVANCE clinical trial.
• To analyze long-term outcomes and risk factors associated with diabetes and vascular disease.

Main Methods:

• A randomized controlled multicenter factorial trial (ADVANCE) was conducted.
• An observational follow-up study (ADVANCE-ON) was performed on surviving participants.
• Epidemiological analyses treated the trial as a cohort study, incorporating biomarker data.

Main Results:

• ADVANCE-ON indicated reduced long-term benefits of blood pressure lowering treatment on mortality, but intensive glucose control showed no sustained survival advantage.
• Intensive glucose control did demonstrate persistent benefits for end-stage renal disease.
• Biomarkers like NT-proBNP and hs-cTnT were strongly associated with macrovascular and microvascular events and all-cause mortality.

Conclusions:

• Integrating post-randomization and epidemiological analyses within clinical trials is valuable.
• Such embedded analyses significantly advance scientific understanding in complex diseases like diabetes and vascular conditions.