Pharmacology Consult

Use of niacin in patients with diabetes

Niacin is highly effective at reducing total cholesterol, LDL and triglycerides, as well as increasing HDL. However, there is some concern over its effect on glucose and whether it is safe to use in patients with diabetes and hyperlipidemia.

Several studies have evaluated the effect of niacin on glucose in patients with diabetes. Goldberg and Jacobson studied the effects of adding niacin as treatment for 13 patients with diabetes and a mean HbA1c of 9.6%. The patients were assigned immediate-release niacin, which was titrated up to 4.5 g per day over four weeks. Niacin-treated patients experienced a 21% increase in HbA1c and a 16% increase in mean plasma glucose.

James R. Taylor, PharmD, CDE
James R. Taylor

The Arterial Disease Multiple Intervention Trial (ADMIT) included 125 patients with hyperlipidemia and type 2 diabetes. Patients were assigned immediate-release niacin, up to 1 g per day, during a 12-week run-in period. Patients were then randomly assigned to receive niacin or placebo for 48 additional weeks; niacin doses averaged about 2.5 g per day. During 48 weeks, niacin was associated with a modest increase in fasting glucose. The increases in fasting glucose were most evident during dose titration periods, with the glucose returning to baseline levels a few weeks later. There was no change in HbA1c in patients assigned niacin; however, those assigned placebo experienced a 0.3% decrease in HbA1c. The researchers concluded that immediate-release niacin in doses less than 3 g per day can safely be used in patients with type 2 diabetes.

Other studies

The Assessment of Diabetes Control and Evaluation of the Efficacy of Niaspan Trial (ADVENT) followed 148 patients with type 2 diabetes who received 1 g or 1.5 g of extended release niacin (Niaspan, Abbott Laboratories) or placebo. Inclusion criteria included stable type 2 diabetes with HbA1c less than 9% and fasting glucose less than 200 mg/dL. After 12 weeks, the researchers noted no significant changes in HbA1c. The mean HbA1c increased from 7.21% to 7.5% in patients receiving 1.5 g of ER niacin. Fasting glucose increased at the week four and eight visits but returned to baseline by the end of the study (week 16). Three percent of the patients discontinued niacin due to hyperglycemia. Based on the researchers’ judgment, glycemic control worsened in 18%, 29% and 12% of patients receiving niacin 1 g per day, 1.5 g per day and placebo, respectively.

The HDL-Atherosclerosis Treatment Study (HATS) evaluated the use of slow release niacin (Slo-Niacin, Upsher-Smith Laboratories) plus simvastatin in 160 patients with coronary artery disease. The mean dose of niacin was 2.4 g per day. Only 25 of these patients had diabetes, and their baseline fasting glucose was less than 180 mg/dL. The baseline fasting glucose in simvastatin plus niacin group was 144 mg/dL vs. 136 mg/dL in the placebo group. In this group, fasting glucose increased at the three-month and eight-month visits. At three months, the simvastatin plus niacin group had a mean fasting glucose of 163 mg/dL vs. 124 mg/dL for the placebo group. At eight months, the mean fasting glucose was 141 mg/dL for active treatment vs. 121 mg/dL for placebo. At one year, the mean fasting glucose was nearly identical for the two groups — 135 mg/dL vs. 133 mg/dL — with the active treatment group being slightly higher.

Abhimanyu Garg, MBBS, MD, and Scott M. Grundy, MD, PhD, conducted a study published in 1990 that determined the effectiveness of nicotinic acid in dyslipidemic patients with non-insulin-dependent diabetes. Patients were assigned to 1.5 g of nicotinic acid three times per day or no therapy for eight weeks. Compared with the control group, patients assigned to nicotinic acid experienced a 24% reduction in total cholesterol, 45% reduction in plasma triglycerides, 58% reduction in very-low LDL and 15% reduction in LDL. Nicotinic acid increased HDL levels by 34%. However, nicotinic acid was associated with the deterioration of glycemic control; it increased mean plasma glucose concentrations by 16%, increased HbA1c levels by 21% and induced marked glycosuria in some patients. The researchers recommended that nicotinic acid be used with caution in this patient population, and not as a first-line hypolipidemic drug in patients with non-insulin-dependent diabetes.

Coronary Drug Project

The Coronary Drug Project evaluated use of 3 g per day of immediate release niacin, along with other agents or placebo, in patients with a past myocardial infarction. No differences were observed in glycosuria or the addition of new diabetes medications in patients receiving niacin vs. placebo. Fasting glucose increased modestly and significantly in the niacin-treated group at one year, two years and four years.

After treatment was discontinued, fasting glucose returned to baseline in the niacin-treated group but increased in the placebo group. Subsequent analysis indicated that the long-term cardiovascular benefits of niacin outweighed any effects on glucose.

Thus, when administered at doses of 2.5 g per day or less, niacin does not appear to have a clinically significant effect on glucose and HbA1c in most patients. Adverse glycemic effects seem to be most prominent during upward titration of niacin. The effects are often transient and return to near baseline levels after a relatively short time. It appears that glycemic effects are more pronounced in patients with type 2 diabetes compared with those without diabetes.

It should also be noted that most of these trials included patients with relatively well-controlled diabetes, so the glycemic effects of niacin in patients with poorly controlled diabetes may be more significant. Niacin offers many CV benefits, and any effect on glucose can typically be accounted for with mild adjustments in diabetes therapy as necessary.

James R. Taylor, PharmD, CDE, is a Clinical Associate Professor in the Department of Pharmacy Practice at the University of Florida in Gainesville.

PERSPECTIVE

Although several larger studies suggest minimal to modest long-term effects of niacin on blood glucose levels in people with type 2 diabetes, it is not clear from reading these studies if medications to control glucose were modified. In fact, the observations that glucose rose most in the earlier phases of the study and then returned toward baseline raise the possibility that the investigators increased medications to treat hyperglycemia during the trials. As to the issue of whether there is even less effect of niacin on glucose levels in people who do not have diabetes, my sense from speaking with colleagues, as well as my own experience, is that individuals with impaired fasting glucose or glucose intolerance are at risk for converting to diabetes. The latter questions should be answered by the AIM-HIGH and HPS2-Thrive studies; those trials should allow for an assessment of whether CV benefits of niacin therapy will outweigh any adverse effects on glucose metabolism.

– Henry N. Ginsberg, MD

Irving Professor of Medicine,
Director of the Irving Institute for Clinical and Translational Research,
Columbia University College of Physicians and Surgeons

For more information:

  • Garg A. JAMA. 1990;246:723-726.
  • Goldberg RB. Mayo Clin Proc. 2008;83:470-478.

Niacin is highly effective at reducing total cholesterol, LDL and triglycerides, as well as increasing HDL. However, there is some concern over its effect on glucose and whether it is safe to use in patients with diabetes and hyperlipidemia.

Several studies have evaluated the effect of niacin on glucose in patients with diabetes. Goldberg and Jacobson studied the effects of adding niacin as treatment for 13 patients with diabetes and a mean HbA1c of 9.6%. The patients were assigned immediate-release niacin, which was titrated up to 4.5 g per day over four weeks. Niacin-treated patients experienced a 21% increase in HbA1c and a 16% increase in mean plasma glucose.

James R. Taylor, PharmD, CDE
James R. Taylor

The Arterial Disease Multiple Intervention Trial (ADMIT) included 125 patients with hyperlipidemia and type 2 diabetes. Patients were assigned immediate-release niacin, up to 1 g per day, during a 12-week run-in period. Patients were then randomly assigned to receive niacin or placebo for 48 additional weeks; niacin doses averaged about 2.5 g per day. During 48 weeks, niacin was associated with a modest increase in fasting glucose. The increases in fasting glucose were most evident during dose titration periods, with the glucose returning to baseline levels a few weeks later. There was no change in HbA1c in patients assigned niacin; however, those assigned placebo experienced a 0.3% decrease in HbA1c. The researchers concluded that immediate-release niacin in doses less than 3 g per day can safely be used in patients with type 2 diabetes.

Other studies

The Assessment of Diabetes Control and Evaluation of the Efficacy of Niaspan Trial (ADVENT) followed 148 patients with type 2 diabetes who received 1 g or 1.5 g of extended release niacin (Niaspan, Abbott Laboratories) or placebo. Inclusion criteria included stable type 2 diabetes with HbA1c less than 9% and fasting glucose less than 200 mg/dL. After 12 weeks, the researchers noted no significant changes in HbA1c. The mean HbA1c increased from 7.21% to 7.5% in patients receiving 1.5 g of ER niacin. Fasting glucose increased at the week four and eight visits but returned to baseline by the end of the study (week 16). Three percent of the patients discontinued niacin due to hyperglycemia. Based on the researchers’ judgment, glycemic control worsened in 18%, 29% and 12% of patients receiving niacin 1 g per day, 1.5 g per day and placebo, respectively.

The HDL-Atherosclerosis Treatment Study (HATS) evaluated the use of slow release niacin (Slo-Niacin, Upsher-Smith Laboratories) plus simvastatin in 160 patients with coronary artery disease. The mean dose of niacin was 2.4 g per day. Only 25 of these patients had diabetes, and their baseline fasting glucose was less than 180 mg/dL. The baseline fasting glucose in simvastatin plus niacin group was 144 mg/dL vs. 136 mg/dL in the placebo group. In this group, fasting glucose increased at the three-month and eight-month visits. At three months, the simvastatin plus niacin group had a mean fasting glucose of 163 mg/dL vs. 124 mg/dL for the placebo group. At eight months, the mean fasting glucose was 141 mg/dL for active treatment vs. 121 mg/dL for placebo. At one year, the mean fasting glucose was nearly identical for the two groups — 135 mg/dL vs. 133 mg/dL — with the active treatment group being slightly higher.

Abhimanyu Garg, MBBS, MD, and Scott M. Grundy, MD, PhD, conducted a study published in 1990 that determined the effectiveness of nicotinic acid in dyslipidemic patients with non-insulin-dependent diabetes. Patients were assigned to 1.5 g of nicotinic acid three times per day or no therapy for eight weeks. Compared with the control group, patients assigned to nicotinic acid experienced a 24% reduction in total cholesterol, 45% reduction in plasma triglycerides, 58% reduction in very-low LDL and 15% reduction in LDL. Nicotinic acid increased HDL levels by 34%. However, nicotinic acid was associated with the deterioration of glycemic control; it increased mean plasma glucose concentrations by 16%, increased HbA1c levels by 21% and induced marked glycosuria in some patients. The researchers recommended that nicotinic acid be used with caution in this patient population, and not as a first-line hypolipidemic drug in patients with non-insulin-dependent diabetes.

Coronary Drug Project

The Coronary Drug Project evaluated use of 3 g per day of immediate release niacin, along with other agents or placebo, in patients with a past myocardial infarction. No differences were observed in glycosuria or the addition of new diabetes medications in patients receiving niacin vs. placebo. Fasting glucose increased modestly and significantly in the niacin-treated group at one year, two years and four years.

After treatment was discontinued, fasting glucose returned to baseline in the niacin-treated group but increased in the placebo group. Subsequent analysis indicated that the long-term cardiovascular benefits of niacin outweighed any effects on glucose.

Thus, when administered at doses of 2.5 g per day or less, niacin does not appear to have a clinically significant effect on glucose and HbA1c in most patients. Adverse glycemic effects seem to be most prominent during upward titration of niacin. The effects are often transient and return to near baseline levels after a relatively short time. It appears that glycemic effects are more pronounced in patients with type 2 diabetes compared with those without diabetes.

It should also be noted that most of these trials included patients with relatively well-controlled diabetes, so the glycemic effects of niacin in patients with poorly controlled diabetes may be more significant. Niacin offers many CV benefits, and any effect on glucose can typically be accounted for with mild adjustments in diabetes therapy as necessary.

James R. Taylor, PharmD, CDE, is a Clinical Associate Professor in the Department of Pharmacy Practice at the University of Florida in Gainesville.

PERSPECTIVE

Although several larger studies suggest minimal to modest long-term effects of niacin on blood glucose levels in people with type 2 diabetes, it is not clear from reading these studies if medications to control glucose were modified. In fact, the observations that glucose rose most in the earlier phases of the study and then returned toward baseline raise the possibility that the investigators increased medications to treat hyperglycemia during the trials. As to the issue of whether there is even less effect of niacin on glucose levels in people who do not have diabetes, my sense from speaking with colleagues, as well as my own experience, is that individuals with impaired fasting glucose or glucose intolerance are at risk for converting to diabetes. The latter questions should be answered by the AIM-HIGH and HPS2-Thrive studies; those trials should allow for an assessment of whether CV benefits of niacin therapy will outweigh any adverse effects on glucose metabolism.

– Henry N. Ginsberg, MD

Irving Professor of Medicine,
Director of the Irving Institute for Clinical and Translational Research,
Columbia University College of Physicians and Surgeons

For more information:

  • Garg A. JAMA. 1990;246:723-726.
  • Goldberg RB. Mayo Clin Proc. 2008;83:470-478.