Differential Treatment Effects on β-Cell Function Using Model-Based Parameters in Type 2 Diabetes: Results From the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE)
Authors' conclusion
Common glucose-lowering medications impact different physiologic components of β-cell function in T2D. Regardless of treatment modality, lower β-cell function associated with early glycemic failure, and β-cell function progressively declined after initial improvement.
Study context
- Population
- Adults with T2D on baseline metformin in GRADEat baseline
- Participants
- 4,712 adults
- Comparison
- Insulin glargine vs glimepiride vs liraglutide vs sitagliptin, added to metformin
- Primary endpoint
- Change in model-based β-cell function parameters (ISR, glucose sensitivity, rate sensitivity, potentiation) and association with glycemic failure (A1C >7.5%; 58.5 mmol/mol)
- Follow-up
- Baseline and 1, 3 and 5 years
Methodological detailscomparative effectiveness, mathematical modeling of OGTTs, linear mixed-effects models, Cox proportional hazards, Classification And Regression Tree (CART) analyses
- Comparative effectiveness
- Mathematical modeling of OGTTs
- Linear mixed-effects models
- Cox proportional hazards
- CART analyses
Primary result
As reported in the abstract
β-cell function parameters by treatment · years 1, 3, 5
- β-cell function parameters increased variably at year 1 across treatments but subsequently declined for all treatments; statistically significant changes
- Liraglutide: greatest increases in insulin secretion rate (ISR), glucose sensitivity and potentiation, remaining above baseline at study end
- Sitagliptin improved glucose sensitivity, with modest effects on other parameters
- Glimepiride temporarily increased ISR and rate sensitivity but minimally increased glucose sensitivity or potentiation
- Rate sensitivity increased most with glargine
Further findings
- Higher β-cell function parameters protective against glycemic deterioration; treatment did not alter this relationship
Original publication
Differential Treatment Effects on β-Cell Function Using Model-Based Parameters in Type 2 Diabetes: Results From the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE). Diabetes Care. Published 25 February 2025. doi:10.
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