Comparative effectiveness of second line oral antidiabetic treatments among people with type 2 diabetes mellitus: emulation of a target trial using routinely collected health data
Authors' conclusion
This emulation study of a target trial found that SGLT-2 inhibitors were more effective than sulfonylureas or DPP-4 inhibitors in lowering mean HbA1c, BMI, and systolic blood pressure and in reducing the hazards of hospital admission for heart failure (v DPP-4 inhibitors) and kidney disease progression (v sulfonylureas), with no evidence of differences in other clinical endpoints.
Study context
- Population
- Adults with T2D initiating second line oral antidiabetic treatment added to metformin; linked primary care, hospital and death data, England, 2015–21
- Participants
- 75,739 adults
- Exposure
- SGLT-2 inhibitors vs DPP-4 inhibitors vs sulfonylureas, added to metformin
- SGLT-2 inhibitorsn = 15,582
- DPP-4 inhibitorsn = 34,464reference
- Sulfonylureasn = 25,693reference
- Outcome
- Absolute change in haemoglobin A1c (HbA1c) between baseline and one year follow-up
- Follow-up
- One year
Methodological detailsinstrumental variable analysis, routinely collected linked health data
- Instrumental variable analysis
- Routinely collected linked health data
Main finding
As reported in the abstract
Mean difference in HbA1c change (instrumental variable analysis) · baseline to one year
Mean difference, mmol/mol (95% CI)
SGLT-2 inhibitorsvs Sulfonylureas
−2.5(−3.7 to −1.3)
SGLT-2 inhibitorsvs DPP-4 inhibitors
−3.2(−4.6 to −1.8)
Observational data: associations, not effects.
Secondary outcomes
| Outcome | HR | |
|---|---|---|
| MACESGLT-2 inhibitorsvs Sulfonylureas | 0.99 (95% CI 0.61–1.62) | |
| MACESGLT-2 inhibitorsvs DPP-4 inhibitors | 0.91 (95% CI 0.51–1.63) | |
| Hospital admission for HFSGLT-2 inhibitorsvs DPP-4 inhibitors | 0.32 (CI 0.12–0.90) | |
| Hospital admission for HFSGLT-2 inhibitorsvs Sulfonylureas | 0.46 (CI 0.20–1.05) | |
| ≥40% decline in eGFRSGLT-2 inhibitorsvs Sulfonylureas | 0.42 (CI 0.22–0.82) | |
| ≥40% decline in eGFRSGLT-2 inhibitorsvs DPP-4 inhibitorsHigh uncertainty | 0.64 (CI 0.29–1.43) | |
| 0.10.31310Hazard ratio (log scale) |
Body mass index (BMI) and systolic blood pressure
- SGLT-2 inhibitors were more effective than sulfonylureas or DPP-4 inhibitors in reducing BMI and systolic blood pressure
Original publication
Comparative effectiveness of second line oral antidiabetic treatments among people with type 2 diabetes mellitus: emulation of a target trial using routinely collected health data. BMJ. Published 8 May 2024. doi:10.
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