In the recent Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE), all four drugs compared (insulin glargine, glimepiride, liraglutide, and sitagliptin) had a beneficial effect on glycemic reduction.1 Glargine and liraglutide performed best, both in achieving and sustaining glycemic outcomes. Of note, severe hypoglycemia was more common in the glimepiride (2.2%) and insulin (1.3%) groups; liraglutide was associated with more weight loss.
In the trial, approximately 5,000 patients with type 2 diabetes (duration <10 years, baseline A1C: 6.8% to 8.5%) on metformin monotherapy were randomized to the four drugs and followed for 5 years. The primary outcome was A1C of 7%; secondary outcomes included A1C of 7.5% and the development of micro- and macrovascular complications.2
The GRADE study provides key evidence to support the next treatment step for patients with type 2 diabetes, without cardiovascular or renal disease, who are already on metformin.1 These results serve as a basis for shared decision making when glycemic goals are not reached with metformin alone.3
- GRADE Study Research Group, Nathan DM, Lachin JM, et al. Glycemia reduction in type 2 diabetes - glycemic outcomes. N Engl J Med 2022;387: 1063-74. doi:10.1056/NEJMoa2200433.
- GRADE Study Research Group, Nathan DM, Lachin JM, et al. Glycemia reduction in type 2 diabetes - microvascular and cardiovascular outcomes. N Engl J Med 2022;387:1075-88. doi:10.1056/NEJMoa2200436.
- Rydén L, Standl E. After metformin - next steps for type 2 diabetes with low cardiovascular risk. N Engl J Med. 2022;387(12):1136-1138. doi:10.1056/NEJMe2210531.