However, data from a secondary analysis of a large randomized controlled trial suggest that glucose elevation with niacin is largely a transient phenomenon lasting several months, “just as the well-known skin flushing with niacin is transient over a similar time period,” Dr. John Guyton, director of the Duke Lipid Clinic, Duke University Medical Center, Durham, North Carolina, told Reuters Health by email.
The analysis, reported in a paper online February 14 in Diabetes Care, also suggests that glucose elevation with niacin often resolves on its own without the need for specific treatment.
“Niacin, an effective agent for treating dyslipidemia, increases fasting glucose and reduces insulin sensitivity via mechanisms that remain unclear,” Dr. Guyton and colleagues note in their paper.
The original trial involved 942 hyperlipidemic patients, who were randomly assigned to ezetimibe/simvastatin (E/S:10/20 mg) alone or with extended-release niacin initiated at 0.5 g/day and increased by 0.5 g every 4 weeks up to 2 g/day over 64 weeks. (See Reuters Health story of March 4, 2010). The secondary analysis looked specifically at the effect of niacin on fasting glucose and new-onset diabetes over 64 weeks.
The researchers report that during the first 24 weeks of treatment, new-onset diabetes occurred more often in patients treated with E/S plus niacin than in those treated with E/S alone (4.4% vs 1.3%; p=0.033). Twenty-five of 28 new-diabetes diagnoses in the E/S+N group occurred by 24 weeks.
During 24 to 64 weeks, an additional 0.5% of patients treated with E/S plus niacin and 1.7% of those treated with E/S developed diabetes (p=0.11).
Overall, Dr. Guyton told Reuters Health, the frequency of new-onset diabetes for the E/S plus niacin group at 64 weeks was only “marginally higher” than that for the E/S group (3.5% vs 2.6%; p=0.66); 1.4% of those taking niacin vs 0.4% of those not taking niacin transiently met criteria for diabetes and then remitted (p=0.46)
“Health care providers may decide to stop niacin on the basis of elevated glucose, despite the usefulness of niacin in improving the lipid profile,” Dr. Guyton commented. Yet, according to this analysis, “the risk for new-onset diabetes with niacin use is less than previously thought. Even when fasting glucose rises above 125 mg/dL after starting niacin, it may decline over the next few months without specific treatment,” he said.
“Consistent with guidelines, niacin is a reasonable option to treat dyslipidemia in patients with or at risk for diabetes, but risk/benefit should be weighed, and glucose should be checked periodically,” the investigators conclude in their paper.
They also note that the incidence rates for diabetes in the study are “somewhat exaggerated” due to frequent fasting glucose sampling (11 times in 64 weeks) compared with fasting glucose monitoring in clinical practice.
They also note that the temporal pattern found in the study may help explain apparently contradictory results in past studies. “Niacin induced hyperglycemia was prominent in studies of short duration (2–12 weeks) and/or at high niacin doses of 3 to 4.5 g/day, whereas longer-term studies at lower doses (3 g or less) showed only modest or statistically nonsignificant effects. Likewise, insulin resistance was found in 2-week niacin studies, whereas a 4-month study showed no such evidence.”
The study was funded by Merck/Schering-Plough Pharmaceuticals, the manufacturer of ezetimibe/simvastatin. Dr. Guyton has received educational and research grants from Merck and other pharmaceutical companies, including Abbott Laboratories, the manufacturer of extended-release niacin. A complete list of author disclosures can be found with the original article.
Diabetes Care, 2012