Comparative effectiveness of SGLT2 inhibitors, GLP-1 receptor agonists, DPP-4 inhibitors, and sulfonylureas on risk of major adverse cardiovascular events: emulation of a randomised target trial using electronic health records
Authors' conclusion
Both SGLT2 inhibitors and GLP-1 receptor agonists were associated with reduced risk of MACE compared with DPP-4 inhibitors or sulfonylureas. DPP-4 inhibitors were associated with reduced risk of MACE compared with sulfonylureas. There was no statistically significant difference in risk of MACE between SGLT2 inhibitors and GLP-1 receptor agonists. The results provide evidence of the real-world comparative effectiveness of the four most commonly used second-line antihyperglycaemics and could guide choice of antihyperglycaemic therapy.
Study context
- Population
- Metformin users with incident use of SGLT2i, GLP-1 RA, DPP-4i or SU between Oct 1, 2016 and Sept 30, 2021, US Department of Veterans Affairs health-care databases; followed up until Dec 31, 2022
- Participants
- 283,998 new users
- Exposure
- SGLT2i vs GLP-1 RA vs DPP-4i vs SU
- SGLT2 inhibitorsn = 46,516
- GLP-1 receptor agonistsn = 26,038
- DPP-4 inhibitorsn = 55,310
- Sulfonylureasn = 156,134reference
- Outcome
- Major adverse cardiovascular events (MACE): composite of stroke, MI and all-cause mortality
Methodological detailsretrospective cohort study, emulation of a four-arm randomised pragmatic clinical trial, overlap weighting, intention-to-treat and per-protocol analyses
- Retrospective cohort study
- Emulation of a four-arm randomised pragmatic clinical trial
- Overlap weighting
- Intention-to-treat and per-protocol analyses
Main finding
As reported in the abstract
MACE
Hazard ratio (95% CI)
SGLT2ivs SU
0.77(0.74–0.80)
GLP-1 RAvs SU
0.78(0.74–0.81)
DPP-4ivs SU
0.90(0.86–0.93)
SGLT2ivs DPP-4i
0.86(0.82–0.89)
GLP-1 RAvs DPP-4i
0.86(0.82–0.90)
SGLT2ivs GLP-1 RA
0.99(0.94–1.04)
Observational data: associations, not effects.
Further findings
| Outcome | HR (95% CI) | |
|---|---|---|
| MACE, per-protocol analyses (maintained use throughout follow-up)SGLT2ivs SUPer-protocol · per-protocol analyses | 0.77 (0.73–0.82) | |
| MACE, per-protocol analyses (maintained use throughout follow-up)GLP-1 RAvs SUPer-protocol · per-protocol analyses | 0.77 (0.72–0.82) | |
| MACE, per-protocol analyses (maintained use throughout follow-up)DPP-4ivs SUPer-protocol · per-protocol analyses | 0.88 (0.83–0.93) | |
| MACE, per-protocol analyses (maintained use throughout follow-up)SGLT2ivs DPP-4iPer-protocol · per-protocol analyses | 0.88 (0.83–0.93) | |
| MACE, per-protocol analyses (maintained use throughout follow-up)GLP-1 RAvs DPP-4iPer-protocol · per-protocol analyses | 0.88 (0.82–0.93) | |
| MACE, per-protocol analyses (maintained use throughout follow-up)SGLT2ivs GLP-1 RAPer-protocol · per-protocol analyses | 1.01 (0.94–1.07) | |
| 0.512Hazard ratio (log scale) |
Original publication
Comparative effectiveness of SGLT2 inhibitors, GLP-1 receptor agonists, DPP-4 inhibitors, and sulfonylureas on risk of major adverse cardiovascular events: emulation of a randomised target trial using electronic health records. Lancet Diabetes Endocrinol. Published 24 July 2023. doi:10.
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