Evaluating the CV and kidney safety profile of linagliptin versus placebo in patients with T2D at high vascular risk
CARMELINA®
Contents
Contents
DPP-4 inhibitors are a common treatment option for glucose lowering in patients with T2D
DPP-4 inhibitors have demonstrated safety for 3P-MACE
The effect of DPP-4 inhibitors on heart failure remains uncertain
The effect of DPP-4 inhibitors on CV safety in patients with kidney disease has been understudied
Diabetes and kidney disease is a stronger factor for mortality than a prior CV event
CV disease and kidney disease are prevalent in patients with T2D
Linagliptin is a single-dose DPP-4 inhibitor with an established clinical efficacy and safety profile
Linagliptin is a single-dose DPP-4 inhibitor with an established clinical efficacy and safety profile
Linagliptin is a single-dose DPP-4 inhibitor with an established clinical efficacy and safety profile
Linagliptin is a single-dose DPP-4 inhibitor with an established clinical efficacy and safety profile
CARMELINA®: a randomised, double-blind, placebo‑controlled cardiovascular outcomes trial
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CARMELINA®: an international trial - patients randomised from 605 sites in 27 countries
CARMELINA®: a trial investigating the CV and kidney safety profile of linagliptin versus placebo
Key inclusion criteria
Prespecified primary and key secondary outcomes
Statistical testing strategy for 3P-MACE and kidney composite
Other prespecified endpoints
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Treatment exposure
Baseline demographics and clinical characteristics
As per the inclusion criteria, patients had established CVD, prevalent CKD or both
Baseline kidney function
CARMELINA® included a significant proportion of patients with kidney disease
Baseline CV risk profile
Baseline CV medications
Contents
Time to first occurrence of 3P-MACE: CV death, non-fatal MI, non‑fatal stroke (primary outcome)
Time to first occurrence of 4P-MACE: 3P-MACE + hospitalisation for unstable angina
Time to first occurrence of 3P-MACE by selected baseline characteristics
Time to first occurrence of key outcomes: Cox regression model
All-cause mortality
All-cause, CV and non-CV mortality
Time to first occurrence of adjudication-confirmed hospitalisation for heart failure
Time to first occurrence of adjudication-confirmed hospitalisation for heart failure by selected baseline characteristics
No increased risk of HHF or HF adverse events with linagliptin
Summary of CV, mortality and heart failure outcomes with linagliptin
Contents
Time to first occurrence of key secondary outcome: sustained ESKD, sustained ≥40% decrease in eGFR from baseline or death due to kidney disease
633 first kidney events contributed to the key secondary outcome: time to first occurrence of sustained ESKD, sustained ≥40% decrease in eGFR from baseline or death due to kidney disease
Time to first occurrence of key secondary outcome by selected baseline characteristics
Time to first occurrence of sustained ESKD or death due to kidney disease
Time to first occurrence of albuminuria progression*
Distribution of first events contributing to the composite microvascular outcome
Kidney and microvascular outcomes with linagliptin
Summary of kidney outcomes with linagliptin
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HbA1c over time
New glucose-lowering therapies introduced post-baseline
Initiation or dose increase of insulin
Body weight and blood pressure over time
Lipids over time
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Adverse events: overall summary
Safety events of particular interest
Safety events of particular interest
Hypoglycaemia
Hypoglycaemia: frequency of events
Hypoglycaemia: rate per 100 patient-years by subgroup
CARMELINA® confirmed the overall safety profile of linagliptin
Contents
CV and heart failure safety profiles in DPP-4 inhibitor CVOTs
CARMELINA® is the first DPP-4 inhibitor to demonstrate a reassuring kidney safety profile based on clinical outcomes
CARMELINA® confirmed the overall safety profile of linagliptin
CARMELINA® fills a data gap as it included patients across the full range of kidney functions
CARMELINA® provided an opportunity to determine heart failure safety in a high-risk population
International guidelines now recommend therapies with proven CV benefit to be used preferentially in patients with T2D and CV disease
Clinical evidence from DPP-4 inhibitor CVOTs
Summary: CARMELINA® reinforces the clinical safety profile of linagliptin in adults with T2D
Sensitivity analyses of time to first occurrence of primary outcome
Sensitivity analyses of time to first occurrence of key secondary outcome
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633 first kidney events contributed to the key secondary outcome: time to first occurrence of sustained ESKD, sustained ≥40% decrease in eGFR from baseline or death due to kidney disease