Comparative effectiveness of alternative second-line oral glucose-lowering therapies for type 2 diabetes: a precision medicine approach applied to routine data
Authors' conclusion
Second-line treatment with SGLT2i is more effective than SU or DPP4i in reducing HbA1c across subgroups of people defined by age, baseline HbA1c and presence of MLTCs. Our evidence complements RCTs in using routinely available information on demographic characteristics, biomarkers and comorbidities to inform an individualised approach.
Study context
- Population
- Individuals with T2D in Clinical Practice Research Datalink (CPRD), England, initiating second-line treatment after metformin between 2015 and 2021
- Participants
- 41,790 individuals
- Exposure
- SGLT2i vs sulfonylureas (SU) vs DPP4i added to metformin as second-line treatment, by age, baseline HbA1c and multiple long-term conditions (MLTCs)
- Outcome
- Change in HbA1c
- Follow-up
- Baseline to 1 year
Methodological detailstarget trial emulation, instrumental variable analysis, primary care-hospital linked data
- Target trial emulation
- Instrumental variable analysis
- Primary care-hospital linked data
Main finding
As reported in the abstract
Mean difference in HbA1c change, by age subgroup · 1 year
Mean difference, mmol/mol (95% CI)
SGLT2ivs SUage 18-49 years; −0.5% [−0.7, −0.4]
−5.74(−7.47 to −4.01)
SGLT2ivs SUage 50-69 years; −0.4% [−0.5, −0.2]
−4.03(−5.61 to −2.44)
SGLT2ivs SUage ≥70 years; −0.3% [−0.4, −0.07]
−2.68(−4.50 to −0.86)
SGLT2ivs DPP4iage 18-49 years; −0.5% [−0.7, −0.4]
−5.80(−7.60 to −4.00)
SGLT2ivs DPP4iage 50-69 years; −0.4% [−0.5, −0.2]
−4.13(−5.82 to −2.45)
SGLT2ivs DPP4iage ≥70 years; −0.3% [−0.4, −0.1]
−3.13(−5.01 to −1.24)
SGLT2ivs SUwithout MLTC; −0.5% [−0.6, −0.3]
−5.37(−7.13 to −3.62)
SGLT2ivs SUwith MLTC; −0.3% [−0.5, −0.2]
−3.72(−5.34 to −2.10)
SGLT2ivs DPP4iwithout MLTC; −0.5% [−0.7, −0.3]
−5.44(−7.27 to −3.61)
SGLT2ivs DPP4iwith MLTC; −0.3% [−0.5, −0.2]
−3.93(−5.64 to −2.21)
Observational data: associations, not effects.
Original publication
Comparative effectiveness of alternative second-line oral glucose-lowering therapies for type 2 diabetes: a precision medicine approach applied to routine data. Diabetologia. Published 31 May 2025. doi:10.
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