Benefits of glucagon-like peptide-1 receptor agonists versus pioglitazone for cardio-hepatic outcomes: a territory-wide target trial emulation
Authors' conclusion
The effects on incident major adverse liver and cardiovascular outcomes were comparable between GLP1RA and pioglitazone, although the risk of incident HF was lower with GLP1RA. Treatment decisions for T2D patients at risk of adverse cardio-hepatic events should be individualized, considering HF risk and the need for weight loss, which if present, GLP1RA may be preferred.
Study context
- Population
- T2D patients newly prescribed GLP-1 RA or pioglitazone between January 2008 and December 2022
- Participants
- 8,922 patients
- Exposure
- GLP-1 RA vs pioglitazone
- GLP1RAn = 4,461
- Pioglitazonen = 4,461reference
- Outcome
- Major adverse liver outcomes (MALO) and MACE
Methodological detailsactive comparator, new user design, territory-wide
- Active comparator, new user design
- Territory-wide
Main finding
As reported in the abstract
GLP1RA vs PioglitazoneHazard ratio (95% CI)
MALO, ITT
0.94(0.66–1.34)
MALO, per-protocol
1.13(0.60–2.15)
MACE, ITT
0.99(0.80–1.22)
MACE, per-protocol
1.10(0.77–1.58)
Observational data: associations, not effects.
Secondary outcomes
| Outcome | HR (95% CI) | |
|---|---|---|
| HFITT; significantly lower with GLP1RA · intention-to-treat analysis | 0.65 (0.51–0.83) | |
| 0.512Hazard ratio (log scale) |
Subgroup and sensitivity analyses
- Results consistent across most subgroup and sensitivity analyses
Original publication
Benefits of glucagon-like peptide-1 receptor agonists versus pioglitazone for cardio-hepatic outcomes: a territory-wide target trial emulation. Cardiovasc Diabetol. Published 31 October 2025. doi:10.
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