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

Contents

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

Contents

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

Contents

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

Contents

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