Glycemia Reduction in Type 2 Diabetes — Glycemic Outcomes

The GRADE trial compared four glucose-lowering medications: insulin glargine, glimepiride, liraglutide, and sitagliptin, when added to metformin for maintaining target HbA₁c levels in patients with type 2 diabetes of <10 years’ duration. Over a mean follow-up of 5 years in 5047 participants, glargine and liraglutide were modestly more effective in maintaining HbA₁c < 7% (primary outcome), with incidence rates of 26.5 and 26.1 per 100 person-years, respectively, versus 30.4 for glimepiride and 38.1 for sitagliptin (P<0.001). All agents lowered HbA₁c, but sitagliptin was least effective, particularly in patients with higher baseline HbA₁c levels. Severe hypoglycemia was rare but highest in the glimepiride group (2.2%), while liraglutide caused more gastrointestinal symptoms and weight loss. Adherence was high across groups. The study concludes that while all four drugs improve glycemic control, glargine and liraglutide offer greater durability, underscoring the need for individualized therapy and more effective long-term glycemic management strategies.

The GRADE trial compared four glucose-lowering medications: insulin glargine, glimepiride, liraglutide, and sitagliptin, when added to metformin for maintaining target HbA₁c levels in patients with type 2 diabetes of <10 years’ duration. Over a mean follow-up of 5 years in 5047 participants, glargine and liraglutide were modestly more effective in maintaining HbA₁c < 7% (primary outcome), with incidence rates of 26.5 and 26.1 per 100 person-years, respectively, versus 30.4 for glimepiride and 38.1 for sitagliptin (P<0.001). All agents lowered HbA₁c, but sitagliptin was least effective, particularly in patients with higher baseline HbA₁c levels. Severe hypoglycemia was rare but highest in the glimepiride group (2.2%), while liraglutide caused more gastrointestinal symptoms and weight loss. Adherence was high across groups. The study concludes that while all four drugs improve glycemic control, glargine and liraglutide offer greater durability, underscoring the need for individualized therapy and more effective long-term glycemic management strategies.