PRONOUNCED BLOOD GLUCOSE-LOWERING EFFECT OF THE ANTILIPOLYTIC DRUG ACIPIMOX IN NONINSULIN-DEPENDENT DIABETES-MELLITUS PATIENTS DURING A 3-DAY INTENSIFIED TREATMENT PERIOD

Acute administration of the antilipolytic nicotinic acid analog acipim ox to patients with noninsulin-dependent diabetes mellitus (NIDDM) is associated with increased peripheral and hepatic insulin sensitivity. However, long term acipimox treatment (250 mg, 3 times/24 h) of NIDDM patients does not improve blood glucose control, possibly due to rebou nd lipolysis. The current study assessed the influence of intensified acipimox administration (125 mg, 12 times/24 h) on diurnal plasma prof iles of glucose, insulin, nonesterified FFA (NEFA), and triglycerides during a 3-day period. Eight NIDDM patients [mean age, 58.9 yr (range, 46-68); mean body mass index, 31.4 kg/m(2) (range, 24.9-39.6)] were i ncluded in a randomized, double blind, placebo-controlled, cross-over study. Blood samples were collected every second hour during the study . The acipimox and placebo treatments were separated by a 2-week washo ut period. Acipimox treatment was associated with reduced diurnal mean plasma concentrations of NEFA [0.26 +/- 0.03 (+/-SEM) vs. 0.63 +/- 0. 06 mmol/L; P < 0.001], triglycerides (1.74 +/- 0.21 vs. 2.10 +/- 0.18 mmol/L; P < 0.03), glucose (12.7 +/- 1.0 vs. 15.8 +/- 1.2 mmol/L; P < 0.002), and insulin (157 +/- 21 vs. 207 +/- 27 pmol/L; P < 0.05). Howe ver, despite the overall reduction in mean NEFA, during acipimox treat ment NEFA increased from days 1-3 (0.18 +/- 0.03 vs. 0.34 +/- 0.04 mmo l/L; P < 0.001), whereas plasma glucose (13.4 +/- 1.2 vs. 12.3 +/- 0.9 mmol/L; P < 0.03) and plasma insulin (168 +/- 23 vs. 148 +/- 17 pmol/ L; P < 0.04) decreased steadily from days 1-3 during active treatment. In conclusion, inhibition of lipolysis using the intensified acipimox treatment regiment was associated with a pronounced blood glucose- an d plasma insulin-lowering effect. However, minor rebound effects of li polysis occurred in some patients despite the presence of allegedly ef fective acipimox levels. This suggests that caution should be employed concerning long term use of acipimox as a hypoglycemic agent in NIDDM patients.