Cardiometabolic & kidneyRandomised controlled trial
Serial assessment of NT-proBNP and high-sensitivity cardiac troponin with glucagon-like peptide-1 receptor agonist therapy in type 2 diabetes: Insights from EXSCEL
- Biomarker cohort of a randomized trial (EXSCEL)
Authors' conclusion
NT-proBNP and cTnI were strong prognostic markers of adverse outcomes in patients with type 2 diabetes and their 1-year increases signaled higher subsequent risk. Baseline cTnI may mark heterogeneity of EQW response, but mortality interactions are hypothesis generating and require confirmation.
Study context
- Population
- Adults with type 2 diabetes randomized to exenatide 2 mg weekly or placebo in EXSCEL, with serial NT-proBNP or cardiac troponin I (cTnI) at baseline and 1 yearbiomarker cohort with serial NT-proBNP or cTnI at baseline and 1 year, EXSCEL randomized 14,752
- Participants
- 4,292 adults
- Comparison
- Baseline concentrations and 1-year change in NT-proBNP and cTnI related to major adverse cardiovascular events (MACE), all-cause mortality (ACM), cardiovascular (CV) death and hospitalization for heart failure (hHF); treatment interaction tested with biomarker by treatment terms
Primary result
As reported in the abstract
Events:
- MACE
- All-cause deaths
- CV deaths
- hHF
MACE
529
all cause deaths
310
CV deaths
193
hHF events
157
Further findings
| Outcome | Estimate | P value |
|---|---|---|
| Baseline NT-proBNP and outcomes — per 1 integer unit baseline NT-proBNP · MACE | adjusted HR 1.63 | P < 0.001 |
| Baseline NT-proBNP and outcomes — per 1 integer unit baseline NT-proBNP · ACM | adjusted HR 1.85 | P < 0.001 |
| Baseline NT-proBNP and outcomes — per 1 integer unit baseline NT-proBNP · CV death | adjusted HR 2.17 | P < 0.001 |
| Baseline NT-proBNP and outcomes — per 1 integer unit baseline NT-proBNP · hHF | adjusted HR 2.17 | P < 0.001 |
| 1-year rise in NT-proBNP and later outcomes — per SD rise in NT-proBNP over 1 year · MACE | HR 1.85 | P < 0.001 |
| 1-year rise in NT-proBNP and later outcomes — per SD rise in NT-proBNP over 1 year · CV death | HR 2.81 | P < 0.001 |
- Baseline NT-proBNP and outcomes: all P < .001
- 1-year rise in NT-proBNP and later outcomes: both P < .001
Baseline cTnI and outcomes
- Baseline cTnI was also prognostic with a nonlinear pattern, with risk rising mainly above the median
Modification of treatment effect by baseline biomarkers
- Baseline NT-proBNP didn't modify treatment effects
- Baseline cTnI didn't modify EQW treatment effect on MACE
- lower rates of CV deaths and hHF with EQW were observed at higher cTnI concentrations
Original publication
Serial assessment of NT-proBNP and high-sensitivity cardiac troponin with glucagon-like peptide-1 receptor agonist therapy in type 2 diabetes: Insights from EXSCEL. Am Heart J. Published 6 May 2026. doi:10.1016/j.ahj.2026.107475
Summarised from the published abstract; every number is checked against it