After Metformin — Next Steps for Type 2 Diabetes with Low Cardiovascular Risk

This editorial evaluates therapeutic choices following metformin initiation in patients with type 2 diabetes who are at low cardiovascular risk. Drawing on findings from the GRADE trial which compared insulin glargine, glimepiride, liraglutide, and sitagliptin over a 5-year follow-up the authors highlight that all agents provided meaningful glycemic control, but liraglutide and insulin glargine achieved superior HbA₁c reductions. Severe hypoglycemia rates were low overall but modestly higher with glargine and glimepiride. Cardiovascular event rates were low given the cohort’s risk profile, though liraglutide showed a 29% relative risk reduction compared to the others. Microvascular outcomes were inconclusive due to underpowered analyses. Limitations include absence of SGLT2 inhibitors and subgroup stratification by glycemic phenotype. The editorial supports individualized agent selection based on metabolic patterns, risk status, and cost considerations, while noting that even older, generic agents remain viable for early-stage diabetes management.

This editorial evaluates therapeutic choices following metformin initiation in patients with type 2 diabetes who are at low cardiovascular risk. Drawing on findings from the GRADE trial which compared insulin glargine, glimepiride, liraglutide, and sitagliptin over a 5-year follow-up the authors highlight that all agents provided meaningful glycemic control, but liraglutide and insulin glargine achieved superior HbA₁c reductions. Severe hypoglycemia rates were low overall but modestly higher with glargine and glimepiride. Cardiovascular event rates were low given the cohort’s risk profile, though liraglutide showed a 29% relative risk reduction compared to the others. Microvascular outcomes were inconclusive due to underpowered analyses. Limitations include absence of SGLT2 inhibitors and subgroup stratification by glycemic phenotype. The editorial supports individualized agent selection based on metabolic patterns, risk status, and cost considerations, while noting that even older, generic agents remain viable for early-stage diabetes management.