Cardiorenal Mortality and Safety Outcomes of GLP ‐1 Receptor Agonists in Type 2 Diabetes With Body Mass Index (BMI) Below 27 kg/m 2 : A Target Trial Emulation
Authors' conclusion
In people with T2D and BMI < 27 kg/m2, GLP-1 RA use was associated with lower coded heart failure risk across all three comparisons, the most consistent finding. The lower all-cause mortality association versus DPP-4i and usual care, absent versus SGLT2i, should be interpreted cautiously as likely reflecting residual confounding rather than a benefit of this magnitude.
Study context
- Population
- Adults with T2D and BMI < 27 kg/m², TriNetX US Collaborative Network, index dates 2020 to 2026matched cohorts
- Comparison
- New GLP-1 RA vs DPP-4i, SGLT2i or usual care
- Outcome
- All-cause mortality
- Follow-up
- Maximum 24 months
Methodological details1:1 propensity score matching, separate comparisons, TriNetX US Collaborative Network
- 1:1 propensity score matching
- Separate comparisons
- TriNetX US Collaborative Network
Main finding
As reported in the abstract
Hazard ratio (95% CI)
GLP-1 RAvs DPP-4i7389 GLP-1 RA users matched
0.61(0.52–0.71)
GLP-1 RAvs SGLT2i8969 GLP-1 RA users matched
0.89(0.76–1.05)
Further findings
| Outcome | HR (95% CI) | |
|---|---|---|
| MACEGLP-1 RAvs DPP-4i | 0.83 (0.71–0.98) | |
| MACEGLP-1 RAvs SGLT2i | 0.81 (0.69–0.95) | |
| Coded HFGLP-1 RAvs DPP-4i | 0.71 (0.60–0.85) | |
| Coded HFGLP-1 RAvs SGLT2i | 0.56 (0.47–0.65) | |
| 0.512Hazard ratio (log scale) |
Coded HF
- Lower coded HF risk across all three comparisons
Safety
- Gastroparesis was more frequent with GLP-1 RA vs DPP-4i
Original publication
Cardiorenal Mortality and Safety Outcomes of GLP ‐1 Receptor Agonists in Type 2 Diabetes With BMI Below 27 kg/m 2 : A Target Trial Emulation. Diabetes Obes Metab. Published 25 August 2026. doi:10.
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