Comparative Effects of Randomized Second-line Therapy for Type 2 Diabetes on a Composite Outcome Incorporating Glycemic Control, Body Weight, and Hypoglycemia: An Analysis of the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE)
Authors' conclusion
Among participants treated with common second-line drug classes for type 2 diabetes, the liraglutide group had the lowest and glimepiride the highest risk of reaching a composite outcome encompassing glycemic deterioration, weight gain, and hypoglycemia. These findings may inform decision-making regarding type 2 diabetes therapy.
Study context
- Population
- People with T2D on metformin randomized to second-line therapy in GRADE; mean follow-up 5.0 years
- Participants
- 5,047 people
- Comparison
- Glargine vs glimepiride vs liraglutide vs sitagliptin, added to metformin
- Primary endpoint
- Composite:
- Time to first HbA1c >7.5% (confirmed)
- ≥5% weight gain
- Severe or recurrent nonsevere hypoglycemia
Methodological detailscomparative effectiveness, four randomized therapies added to metformin
- Comparative effectiveness
- Four randomized therapies added to metformin
Primary result
As reported in the abstract
Risk of composite outcome (events per 100 PTYs)
Liraglutide
19 per 100 PTYs
Sitagliptin
26 per 100 PTYs
Glargine
29 per 100 PTYs
Glimepiride
40 per 100 PTYs
Further findings
Weight gain and hypoglycemia
- Risk order same as composite: lowest with liraglutide, then sitagliptin, glargine, glimepiride
Glycemic deterioration
- Risk lowest with glargine, followed by liraglutide, glimepiride, and sitagliptin
Heterogeneity across prespecified covariates
- No significant heterogeneity in risk of composite outcome
Treatment satisfaction
- Modestly but significantly lower in participants who reached the composite outcome
Original publication
Comparative Effects of Randomized Second-line Therapy for Type 2 Diabetes on a Composite Outcome Incorporating Glycemic Control, Body Weight, and Hypoglycemia: An Analysis of the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE). Diabetes Care. Published 9 January 2024. doi:10.
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