Combination of Glucagon-Like Peptide 1 Receptor Agonist and Thiazolidinedione for Mortality and Cardiovascular Outcomes in Patients With Type 2 Diabetes
An erratum to this article was published (JAMA Netw Open, 2 Jun 2025 ↗)
Authors' conclusion
In this cohort study of patients with type 2 diabetes, combination therapy with a GLP-1RA plus thiazolidinedione was associated with significantly lower hazards of mortality and cardiovascular complications compared with nonuse. The findings suggest that GLP-1RAs may mitigate the adverse cardiovascular effects of thiazolidinedione.
Study context
- Population
- Patients older than 20 years with T2D who received a GLP-1 RA or TZD, 2011–2020, Taiwan's National Health Insurance Research Database; mean (SD) age 58.3 (11.9) years, 45.5% female110,411 users + matched nonusers
- Participants
- 220,822 participants
- Exposure
- GLP-1 RA plus TZD combination, GLP-1 RA monotherapy or TZD monotherapy vs nonuse
- GLP-1RA plus thiazolidinedionen = 30,682
- GLP-1RAn = 47,526
- Thiazolidinedionen = 32,203
- Outcome
- All-cause mortality, MACE, cardiovascular mortality, cardiovascular complications and hypoglycemia
Methodological detailsnationwide, propensity score-matched nonusers
- Nationwide
- Propensity score-matched nonusers
Main finding
As reported in the abstract
All-cause mortality, MACE and cardiovascular mortality
Estimate (95% CI)P value
GLP-1RA plus thiazolidinedionevs Nonusers
aHR, all-cause mortality 0.20(0.19–0.21)
P < 0.001GLP-1RA plus thiazolidinedionevs Nonusers
aHR, MACE 0.85(0.82–0.89)
P < 0.001GLP-1RA plus thiazolidinedionevs Nonusers
aHR, cardiovascular mortality 0.20(0.18–0.23)
P < 0.001Thiazolidinedionevs GLP-1RA
aHR, all-cause mortality 1.29(1.24–1.34)
P < 0.001Thiazolidinedionevs GLP-1RA
aHR, cardiovascular mortality 1.28(1.13–1.45)
P < 0.001Observational data: associations, not effects.
Safety
| Outcome | aHR (95% CI) | P value | |
|---|---|---|---|
| HypoglycemiaGLP-1RA plus thiazolidinedionevs Nonusers | 1.61 (1.43–1.82) | P < 0.001 | |
| HypoglycemiaThiazolidinedionevs Nonusers | 1.69 (1.51–1.90) | P < 0.001 | |
| 0.512Adjusted hazard ratio (log scale) |
Hypoglycemia
- Hypoglycemia risk was mitigated with prolonged use
Original publication
Combination of Glucagon-Like Peptide 1 Receptor Agonist and Thiazolidinedione for Mortality and Cardiovascular Outcomes in Patients With Type 2 Diabetes. JAMA Netw Open. Published 3 March 2025. doi:10.
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