Comparing Effectiveness and Safety of SGLT2 Inhibitors vs DPP-4 Inhibitors in Patients With Type 2 Diabetes and Varying Baseline HbA 1c Levels
An erratum to this article was published (JAMA Intern Med, 1 Mar 2025 ↗)
Authors' conclusion
In this comparative effectiveness and safety research study among adults with T2D, SGLT2i vs DPP-4i treatment initiators had a reduced risk of modified MACE and HHF, an increased risk of genital infections and DKA, and a lower risk of AKI, regardless of baseline HbA1c.
Study context
- Population
- Commercially insured adults with T2D initiating SGLT2i or DPP-4i, with ≥1 hemoglobin A1c (HbA1c) result within 3 months before initiation87,274 propensity score-matched
- Participants
- 144,614 participants
- Exposure
- SGLT2i vs DPP-4i
- SGLT2in = 60,523
- DPP-4in = 84,091reference
- Outcome
- Modified MACE (MI, stroke or all-cause death) and hospitalization for HF (HHF)
- Follow-up
- Mean 8 months
Methodological detailsnew-user cohort, propensity-score matched (1:1), commercially insured, 128 covariates controlled
- New-user cohort
- Propensity-score matched (1:1)
- Commercially insured
- 128 covariates controlled
Main finding
As reported in the abstract
SGLT2i
- Modified MACE incidence rate (IR) per 1000 person-years
- 17.13
- Hospitalization for heart failure (HHF) IR per 1000 person-years
- 3.68
DPP-4i
- Modified MACE IR per 1000 person-years
- 20.18
- HHF IR per 1000 person-years
- 8.08
Modified MACE incidence rate (IR) per 1000 person-years
SGLT2i17.13
DPP-4i20.18
Hospitalization for heart failure (HHF) IR per 1000 person-years
SGLT2i3.68
DPP-4i8.08
SGLT2i vs DPP-4iHazard ratio (95% CI)
Modified MACE
0.85(0.75–0.95)
HHF
0.46(0.35–0.57)
SGLT2i vs DPP-4iRD, per 1000 person-years (95% CI)
Modified MACE
−3.02(−5.23 to −0.80)
HHF
−4.37(−5.62 to −3.12)
Observational data: associations, not effects.
Safety
| Outcome | SGLT2i | DPP-4i | HR (95% CI) | |
|---|---|---|---|---|
| Genital infections, HbA1c 7.5% to 9% (subgroup) | 3.10 (2.68–3.58) | |||
| IR per 1000 person-years | 68.5 | 22.8 | ||
| 0.20.5125Hazard ratio (log scale) |
| Outcome | RD (per 1000 person-years) (95% CI) | |
|---|---|---|
| Genital infections, HbA1c 7.5% to 9% (subgroup) | 46.22 (40.54–51.90) | |
| −50050100Difference, per 1000 person-years (linear scale) |
- Genital infections, HbA1c 7.5% to 9% (subgroup): more pronounced risk in this HbA1c stratum
Genital infections, diabetic ketoacidosis (DKA), acute kidney injury (AKI)
- SGLT2i: increased risk of genital infections and DKA, reduced AKI risk vs DPP-4i; consistent by HbA1c level
Original publication
Comparing Effectiveness and Safety of SGLT2 Inhibitors vs DPP-4 Inhibitors in Patients With Type 2 Diabetes and Varying Baseline HbA 1c Levels. JAMA Intern Med. Published 1 March 2023. doi:10.
Summarised from the published abstract; every number is checked against it