Ranolazine: from the treatment of chronic

ischemic heart disease to the diabetic patient

Edoardo Mannucci

Diabetes AgencyCareggi teaching hospital,

Firenze, Italy

CARDIOVASCULAR THERAPY AND DIABETES

• Many cardiovascular drugs and procedures show a

reduced efficacy in patients with diabetes (e.g., ASA,

or PTCA)

• Many cardiovascular drugs increase blood glucose in

patients with diabetes (e.g., beta-blockers or

diuretics)

CARISA trial: ranolazine vs placebo, 12 weeksPatients (N=189) with stable angina – 189 with diabetes

927 patients with T2DMStable angina

Recurrent ischemia; patients with ACS

Group 1: ranolazine 3 wkGroup 2: ranolazine 2 wk, pbo 1wkGroup 3: placebo 3 wk

ENDOTHELIAL ACTIONS OF RANOLAZINE

• Antiinflammatory action

• Antioxidant properties

• Direct inhibition of receptors mediating late sodium

channel current on endothelial cells

• Improvement of glucose control

927 patients with T2DMStable angina

Patients with ACS

MECHANISMS OF GLUCOSE LOWERING ACTION

• Reduced glucogeonesis due to inhibition of lipid

oxydation (?)

• Increased insulin sensitivity (?)

CARISA trial: ranolazine vs placebo, 12 weeksPatients (N=189) with stable angina – 189 with diabetes

STZ-diabetic mice, ranolazine vs vehicle

STZ-diabetic mice, ranolazine vs vehicle

Oral glucose tolerance test

MECHANISMS OF GLUCOSE LOWERING ACTION

• Reduced glucogeonesis due to inhibition of lipid

oxydation (?)

• Increased insulin sensitivity (?)

• Stimulation of insulin secretion (via beta-cell Na

channels) (?)

• Increased beta-cell mass in the long term (?)

STZ-diabetic mice, ranolazine vs vehicle

STZ-diabetic mice, ranolazine vs vehicle