CAROLINA subgroup analysis:
CV safety of linagliptin versus glimepiride in Asian patients with relatively early T2D at increased CV risk

Why do we need the CAROLINA trial?

International guidelines now recommend therapies with a proven CV benefit profile to be used preferentially in patients with T2D and CV disease, marking a new era in diabetes management1-4

However, a need remains for additional glucose-lowering medications with a proven long-term CV safety profile; DPP-4 inhibitors and sulphonylureas represent two common add-on treatment choices2,3

In the placebo-controlled CVOT CARMELINA, linagliptin demonstrated a long-term CV and kidney safety profile in patients with T2D, including those with CV and/or kidney disease5

CAROLINA uniquely assessed the long-term CV safety profile of linagliptin versus glimepiride in patients with relatively early T2D at increased CV risk6

CAROLINA was specifically designed to evaluate the long-term CV safety profile (3P-MACE) of linagliptin versus glimepiride6

The CV safety profile of linagliptin versus glimepiride was assessed using 3P-MACE (CV death, non-fatal MI, non‑fatal stroke)

CAROLINA studied a patient population with relatively early T2D at increased CV risk6

The baseline characteristics of Asian patients in CAROLINA were generally similar between treatment groups and to the overall trial population7

There were more Asian patients (77%) with ≥2 defined CV risk factors compared with the overall population (37%)6,7

CAROLINA demonstrated data for the long-term CV and overall safety profile of linagliptin versus glimepiride

What is the meaning of the CAROLINA results?

CARMELINA established the long-term CV and kidney safety profile of linagliptin versus placebo and demonstrated no increased risk of HHF, even in patients at high risk of heart failure5

CAROLINA, the longest DPP-4 inhibitor CVOT of a DPP-4 inhibitor to date, reaffirmed the long-term CV safety profile of linagliptin compared with glimepiride in patients with relatively early T2D and at increased CV risk6

With similar overall levels of glucose control, linagliptin demonstrated a consistently lower incidence of hypoglycaemic events and modestly lower body weight compared with glimepiride6

CARMELINA and CAROLINA constitute a comprehensive CVOT programme demonstrating the long-term safety profile of linagliptin in a broad range of patients with T2D, with consistent results in Asian patients5,6

CAROLINA showed no relative CV benefit or risk with linagliptin or glimepiride.6 To ensure optimal CV benefit for patients with T2D and CV disease, contemporary treatment guidelines recommend that an SGLT2 inhibitor or a GLP-1 RA with proven CV benefit is added to metformin1–4

Want to know more about the CAROLINA trial? Click here for further resources

For information on the CARMELINA trial, please click here

Logo Carmelina
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A robust CVOT programme assessing the long-term
CV and kidney safety profile of linagliptin

*To ensure an adequate level of glycaemic control for patients, investigators could institute glycaemic rescue medication, provided specific protocol criteria were met6;
Starting dose of 1 mg/day up-titrated to a potential maximum of 4 mg/day every 4 weeks for the first 16 weeks. Doses could be up- or down-titrated at any point of the
study as required6; Composite of 3P-MACE plus time to first occurrence of hospitalisation for unstable angina6; §Between end of titration and final visit6; 3P-MACE: CV
death, non-fatal MI, non-fatal stroke6; **Because the confirmatory test for superiority of the primary outcome, 3P-MACE, in the overall population was not significant (p=0.76 for superiority),
all subsequent analyses are considered exploratory.y6
3P-MACE, 3-point major adverse cardiovascular events; 4P-MACE, 4-point major adverse cardiovascular events; BL, baseline; CV, cardiovascular; CVOT, cardiovascular
outcomes trial; DPP-4, dipeptidyl peptidase-4; GLP-1 RA, glucagon-like peptide-1 receptor agonist; HbA1c, glycated haemoglobin; HHF, hospitalisation for heart failure;
MI, myocardial infarction; T2D, type 2 diabetes
1. Diabetes Canada Clinical Practice Guidelines Expert Committee. Can J Diabetes 2018;42:S162; 2. American Diabetes Association. Diabetes Care 2020;43:S1; 3. Buse JB
et al. Diabetes Care 2020;43:487; 4. Diabetes Canada Clinical Practice Guidelines Expert Committee. Can J Diabetes 2018;42:S201; 5. Rosenstock J et al. JAMA 2019;321:69;
6. Rosenstock J et al. JAMA 2019;322:1155; 7. Kadowaki T et al. Diabetol Int 2020; doi: 10.1007/s13340-020-00447-5; 8. Rosenstock J et al. ADA 2019; oral presentation

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