Cardiometabolic & kidneySecondary analysis
Hypoglycemia and Cardiovascular Outcomes in the CARMELINA and CAROLINA Trials of Linagliptin
- Secondary analysis of the CARMELINA and CAROLINA randomised trials
- post hoc
- multinational
- double-blind
Authors' conclusion
This study found bidirectional associations between hypoglycemia and CV outcomes in the CARMELINA trial but no associations in either direction in the CAROLINA trial, challenging the notion that hypoglycemia causes adverse CV events.
Study context
- Population
- Adults with T2DM at high cardiovascular (CV) risk with or without high kidney risk, in trials of linagliptin (vs placebo in CARMELINA; vs glimepiride in CAROLINA)CARMELINA 6979
- Comparison
- Hypoglycaemia vs no hypoglycaemia for subsequent events
- Primary endpoint
- 3P-MACE (CV death, myocardial infarction (MI) or stroke) plus hospitalization for heart failure (HF) after first hypoglycemic episode; and subsequent hypoglycemia after nonfatal CV events
Primary result
As reported in the abstract
Associations between hypoglycemia and CV events, by trial
Hazard ratio (95% CI)
Hypoglycemia → subsequent 3P-MACE plus HF hospitalization (CARMELINA)
1.23(1.04–1.46)
Nonfatal CV events → subsequent hypoglycemia (CARMELINA)
1.39(1.06–1.83)
Hypoglycemia → subsequent 3P-MACE plus HF hospitalization (CAROLINA)
1.00(0.76–1.32)
Nonfatal CV events → subsequent hypoglycemia (CAROLINA)
1.44(0.96–2.16)
Further findings
CV events within 60 days after hypoglycemia (sensitivity analysis)
- Either no association or too few events to analyze
Original publication
Hypoglycemia and Cardiovascular Outcomes in the CARMELINA and CAROLINA Trials of Linagliptin. JAMA Cardiol. Published 1 February 2024. doi:10.1001/jamacardio.2023.4602
Summarised from the published abstract; every number is checked against it