Anti-ischemic agent reduces HbA1c levels in patients with diabetes

November 7, 2007

Ranolazine extended-release significantly reduced the level of hemoglobin (Hb) A1c in patients with diabetes, allowing more of them to achieve the clinical HbA1c treatment target of less than 7.0%.

Ranolazine extended-release significantly reduced the level of hemoglobin (Hb) A1c in patients with diabetes, allowing more of them to achieve the clinical HbA1c treatment target of less than 7.0%.

These findings were obtained in a post-hoc analysis of the MERLIN (Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes) study, and were reported during the American Heart Association Scientific Sessions, Nov. 3-7, 2007, in Orlando, by David Morrow, MD, MPH.

"If a significant hypoglycemic effect [of ranolazine] is supported by ongoing mechanistic studies, ranolazine would be extremely attractive for the treatment of patients with coronary artery disease and diabetes mellitus," said Dr Morrow, a physician in the cardiovascular division at Brigham and Women's Hospital, Boston, and an assistant professor of medicine at Harvard Medical School, Boston. Preclinical studies have shown that ranolazine increases glucose-stimulated insulin secretion in pancreatic islet cells and improves glucose homeostasis.

MERLIN included 6560 patients with non-ST-elevation ACS with clinical indicators of moderate to high risk of recurrent ischemic events. Thirty-five percent of the study population had diabetes at baseline. Patients were randomized to ranolazine, initiated intravenously followed by its oral extended-release formulation (1,000 mg/bid), or placebo for approximately 12 months in addition to standard medical therapy.

The primary endpoint - a composite of cardiovascular death, MI, or recurrent ischemia - occurred in 21.8% of patients randomized to ranolazine and 23.5% randomized to placebo, a nonsignificant difference.

In the patients randomized to ranolazine, however, there were significant reductions in incidence of recurrent ischemia (13% reduction; P =.03), worsening angina (23% reduction; P =.023), and the need for antianginal therapy (19% reduction; P =.006) compared with placebo.

The risk of clinically significant arrhythmias on Holter monitoring was reduced by a significant 11% (P

The new analysis presented here included 4306 patients from MERLIN for whom serial HbA1c data were available. All patients with diabetes were on a background of standard treatments for diabetes. In the overall cohort, randomization to ranolazine resulted in a drop of HbA1c from 6.2% to 5.9% at month 4, whereas there was no change in HbA1c in those randomized to placebo.

In the cohort with diabetes, ranolazine was associated with a significant reduction in HbA1c of 0.64% relative to placebo at 4 months (P

"The reduction in HbA1c observed with ranolazine is especially striking because the effects were observed on top of multiple other anti-diabetic drugs used as part of standard therapy," Dr Morrow said.

Patients assigned to ranolazine were also significantly more likely (P

Patients without diabetes had a 32% reduction (P =.03) in developing impaired fasting glucose or an HbA1c level greater than 6.0%.