Glycemia Reduction in Type 2 Diabetes — Microvascular and Cardiovascular Outcomes

This GRADE trial analysis compared microvascular and cardiovascular outcomes across four glucose-lowering agents: glargine, glimepiride, liraglutide, and sitagliptin when added to metformin in 5047 patients with type 2 diabetes. Over a mean of 5 years, no material differences were found among groups in hypertension, dyslipidemia, renal impairment (eGFR < 60 ml/min/1.73m²), albuminuria, or diabetic neuropathy. Cumulative incidences for moderately increased albuminuria (≥30 mg/g) reached ~15%, severely increased albuminuria (~8%), renal impairment (~20%), and neuropathy (~70%). Cardiovascular event rates were low overall, reflecting a low-risk cohort. However, liraglutide showed a lower cumulative incidence of any cardiovascular disease (HR: 0.71 vs. others), particularly against sitagliptin and glimepiride. Differences were not observed for MACE, heart failure hospitalization, or mortality. Per-protocol analyses suggested modest benefit from liraglutide or sitagliptin for early kidney markers, though not for sustained renal function. The trial concludes that all agents were safe and similarly effective for most endpoints, but liraglutide may confer added cardiovascular protection even in early-stage diabetes.

This GRADE trial analysis compared microvascular and cardiovascular outcomes across four glucose-lowering agents: glargine, glimepiride, liraglutide, and sitagliptin when added to metformin in 5047 patients with type 2 diabetes. Over a mean of 5 years, no material differences were found among groups in hypertension, dyslipidemia, renal impairment (eGFR < 60 ml/min/1.73m²), albuminuria, or diabetic neuropathy. Cumulative incidences for moderately increased albuminuria (≥30 mg/g) reached ~15%, severely increased albuminuria (~8%), renal impairment (~20%), and neuropathy (~70%). Cardiovascular event rates were low overall, reflecting a low-risk cohort. However, liraglutide showed a lower cumulative incidence of any cardiovascular disease (HR: 0.71 vs. others), particularly against sitagliptin and glimepiride. Differences were not observed for MACE, heart failure hospitalization, or mortality. Per-protocol analyses suggested modest benefit from liraglutide or sitagliptin for early kidney markers, though not for sustained renal function. The trial concludes that all agents were safe and similarly effective for most endpoints, but liraglutide may confer added cardiovascular protection even in early-stage diabetes.