Download file (Risk of Hyperglycemia due to Lipid Lowering Agents )

Hannah Allegretto
06/2012
Drug Information Question
Question: “Which lipid-lowering agents are linked to hyperglycemia?”
Answer:
Several lipid-lowering agents have recently been linked to causing hyperglycemia
in the individuals taking these agents. Current evidence suggests that niacin, as well as
statins, are linked with the adverse effect of hyperglycemia.
Niacin, also known as nicotinic acid, is a B-complex vitamin shown to raise HDL
levels and lower serum cholesterol and triglycerides.1 Although niacin has been proven to
have several favorable outcomes on lipid profiles, it should be used cautiously in patients
with diabetes. In a study published in JAMA, niacin therapy was used for dyslipidemia in
non-insulin-dependent diabetes mellitus (NIDDM). Nicotinic acid therapy was correlated
with a deterioration of glycemic control, which was seen with a 16% increase in mean
plasma glucose concentrations and a 21% increase in glycosylated hemoglobin levels.2
The relationship between niacin therapy and hyperglycemia is not completely
understood, but it is hypothesized that it may be due to a stimulation of gluconeogenesis,
development of insulin resistance, or interference with triglyceride synthesis. Due to the
established link between niacin and reports of hyperglycemia, niacin should be used with
caution in patients with glucose intolerance or those at risk for the development of
diabetes mellitus.
Although the link between niacin and hyperglycemia has been established for
several years, reports linking statins with hyperglycemia are relatively new. Several
reviews have been performed on the relationship between statin therapy and
hyperglycemia, and although the results are not completely conclusive, a relationship
does seem to exist.
Statins therapy has been shown to significantly reduce cardiovascular events in
patients regardless of a history of diabetes. Furthermore, intensive-dose statin therapy has
been proven to further reduce cardiovascular events in patients.3 Although statins have
several benefits for the patients, side effects must also be considered when prescribing
this class of medication. In a pooled analysis of five major trials evaluating statin therapy,
an increased risk of new-onset diabetes was associated with intensive-dose statin therapy
when compared to moderate-dose statin therapy. Patients on high doses of atorvastatin
developed greater insulin resistance, higher insulin levels, and higher A1C values.3
Another data analysis investigated the effect of statin use on fasting plasma glucose
(FPG) in patients with or without diabetes. Statin users had a mean increase in FPG of
10mg/dL over a two year follow up. Consistent with a previous study, atorvastatin was
found to have a greater risk of developing an increasing A1C, although atorvastatin was
superior in decreasing LDL levels when compared to pravastatin.4
The JUPITER trial, which was focused on evaluating the effectiveness of
rosuvastatin, reported a small but significant increase in the rate of physician-reported
diabetes along with a small increase in the median glycated hemoglobin. These results are
consistent for other trials evaluating statins, but further studies will have to be conducted
to find the exact extent to which statins cause the most incidents of hypeglycemia.
According to literature available, I would suggest avoiding atorvastatin in patients at risk
for developing diabetes in the future.
1. Schwartz M. Severe reversible hyperglycemia as a consequence of niacin therapy.
Arch Intern Med. 1993; 153: 2050-52.
2.
Garg A, Grundy S. Nicotinic acid as therapy for dyslipidemia in non-insulindependent diabetes mellitus. JAMA. 1990; 264: 723-26.
3. Preiss D, Seshasai SRK, Welsh P. Risk of incident diabetes with intensive-dose
compared to moderate-dose statin therapy. JAMA. 2011; 305: 2556-64.
4. Sikhija R, Prayaga S, Marashdeh M et al. Effect of statins on fasting plasma
glucose in diabetic and nondiabetic patients. J Investig Med. 2009; 57: 495-99.