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