CAROLINA:
evaluating the long-term CV safety profile of linagliptin versus glimepiride in patients with relatively early T2D at increased CV risk

Why do we need the CAROLINA trial?

In patients with T2D and ASCVD, many societies now recommend that the initial choice of glucose-lowering therapy following metformin should be based on evidence of proven CV benefit1–4

When other glucose-lowering medications are needed, DPP-4 inhibitors and sulphonylureas represent two common add-on treatment choices3

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 linagliptin6

The CV safety profile of linagliptin was assessed using 3P-MACE: CV death, non-fatal MI, non-fatal stroke

What is the meaning of the CAROLINA results?5–7

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

• CAROLINA, the longest DPP-4 inhibitor CVOT
to date, confirmed the long-term CV safety
profile of linagliptin relative to glimepiride in
patients with relatively early T2D at increased
CV risk

• With similar overall levels of glucose control, a
lower incidence of hypoglycaemic events and
modestly lower body weight was observed with
linagliptin compared to glimepiride

• CAROLINA and CARMELINA constitute a
comprehensive CVOT programme
demonstrating the long-term safety profile of
linagliptin in a broad range of patients with T2D

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

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

For information on the CARMELINA trial, please click here

Logo Carmelina
Logo Carolina

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 met; 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 required; Composite of 3P-MACE plus time to first occurrence of hospitalisation for unstable angina; §Between end of titration and final visit
3P-MACE, 3-point major adverse cardiovascular events; 4P-MACE, 4-point major adverse cardiovascular events; ASCVD, atherosclerotic cardiovascular disease; CV, cardiovascular; CVOT, cardiovascular outcomes trial; DPP-4, dipeptidyl peptidase-4; HbA1c, glycated haemoglobin; 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 2019;42:S1;
3. Davies MJ et al. Diabetes Care 2018;41:2669; 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; doi: 10.1001/jama.2019.13772; 7. Rosenstock J et al. ADA 2019; oral presentation;
8. FDA. Guidance for Industry. 2008. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm071627.pdf (accessed Aug 2019)

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