Comparative Effectiveness of Second-Line Antihyperglycemic Agents for Cardiovascular Outcomes: A Multinational, Federated Analysis of LEGEND-T2DM
Authors' conclusion
In patients with T2DM and CVD, comparable cardiovascular risk reduction was found with SGLT2is and GLP-1 RAs, with both agents more effective than DPP4is, which in turn were more effective than SUs.
Study context
- Population
- Patients with T2DM and cardiovascular disease (CVD) on metformin monotherapy initiating a second-line agent (LEGEND-T2DM network, 1992–2021)10 data sources
- Participants
- 1,492,855 patients
- Exposure
- SGLT2is vs GLP-1 RAs vs DPP4is vs SUs as second-line agents
- Outcome
- 3-point MACE (MI, stroke, death) and 4-point MACE (3-point MACE plus HF hospitalization)
Methodological detailsactive-comparator target trial emulation, large-scale propensity score models, on-treatment analysis, random-effects meta-analysis, 10 federated international data sources
- Active-comparator target trial emulation
- Large-scale propensity score models
- On-treatment analysis
- Random-effects meta-analysis
- 10 federated international data sources
Main finding
As reported in the abstract
3-point MACE
Hazard ratio (95% CI)
SGLT2is vs DPP4is
0.89(0.79–1.00)
GLP-1 RAs vs DPP4is
0.83(0.70–0.98)
SGLT2is vs SUs
0.76(0.65–0.89)
GLP-1 RAs vs SUs
0.72(0.58–0.88)
DPP4is vs SUs
0.87(0.79–0.95)
SGLT2is vs GLP-1 RAsno significant difference
1.06(0.96–1.17)
Observational data: associations, not effects.
Further findings
| Outcome | HR (95% CI) | |
|---|---|---|
| 4-point MACE · no significant difference | 1.05 (0.97–1.13) | |
| 0.512Hazard ratio (log scale) |
- 4-point major adverse cardiovascular events (MACE): 41,447 4-point MACE events
4-point MACE
- Same pattern as for 3-point MACE
Original publication
Comparative Effectiveness of Second-Line Antihyperglycemic Agents for Cardiovascular Outcomes: A Multinational, Federated Analysis of LEGEND-T2DM. J Am Coll Cardiol. Published 3 September 2024. doi:10.
Summarised from the published abstract; every number is checked against it