- Question
- Which of four commonly used glucose-lowering drugs added to metformin is most effective at achieving and maintaining target glycated hemoglobin in people with type 2 diabetes?
- Design
- Randomized, open-label (unmasked) comparative effectiveness trial with four groups. It included 5047 participants followed for a mean of 5.0 years.
- Population
- People with type 2 diabetes of less than 10 years' duration, receiving metformin, with glycated hemoglobin of 6.8 to 8.5%. Of participants, 19.8% were Black and 18.6% were Hispanic or Latinx.
- Intervention
- One of three drugs was added to metformin: insulin glargine U-100, liraglutide (a GLP-1 receptor agonist), or sitagliptin (a DPP-4 inhibitor), each in a separate group.
- Control
- Glimepiride (a sulfonylurea) added to metformin; the design compares all four drugs with one another, without a placebo.
- Primary outcome
- Glycated hemoglobin of 7.0% or higher, measured quarterly and subsequently confirmed. The secondary metabolic outcome was a confirmed glycated hemoglobin level greater than 7.5%.
- Results
- The cumulative incidence of the primary outcome differed significantly across groups (P<0.001): glargine 26.5 and liraglutide 26.1 per 100 participant-years, versus glimepiride 30.4 and sitagliptin 38.1. Results for glycated hemoglobin >7.5% paralleled those of the primary outcome.
- Safety
- Severe hypoglycemia was rare but more frequent with glimepiride (2.2%) than with glargine (1.3%), liraglutide (1.0%), or sitagliptin (0.7%). Liraglutide caused more gastrointestinal side effects and greater weight loss.
- Conclusion
- All four drugs lowered glycated hemoglobin when added to metformin, but glargine and liraglutide were modestly more effective at achieving and maintaining the target.
- Why it matters
- It provided direct, long-term comparative evidence to guide the choice of second-line drug after metformin in type 2 diabetes, showing modest but consistent differences in glycemic control along with distinct safety and tolerability profiles.
Card generated automatically with AI from the abstract of the original publication and the trial registry; every figure was checked against those sources. It may contain errors: verify the data at the source before using it for clinical decisions.
Generated on October 15, 2026