Elevated serum liver enzymes in obesity: a dilemma during clinical trials.

We found that 17 out of 60 (28.3 percent) obese, otherwise healthy volunteers had elevated serum alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT) or alkaline phosphatase (AP) at least once in the course of a 12 week clinical trial. ALAT was the most commonly elevated serum aminotransferase occurring in 16 out of the 17 participants. Its range of elevation, as a percentage of the upper limit of normal (ULN) at screening was 102-164 percent (mean +/- s.d.; 127 percent +/- 18.4). Three participants had slight elevations of AP (112 percent, 113 percent, 119 percent of ULN). One participant had a minor elevation of ASAT (107 percent of ULN at screening). Of the 17 participants with elevated aminotransferases and AP, six were randomized to placebo, seven were treated with the low dose and four with the high dose of the new medication. Study participants having elevated enzymes had higher ideal body weight (IBW) than the group with normal values at screening (162 +/- 10 percent IBW, 152 +/- 11 percent IBW respectively), and at week 8 (152 +/- 3 percent IBW, 146 +/- 2 percent respectively) (P less than 0.05). The corresponding body mass index (BMI) values are 36.8 +/- 2.8 for the participants with elevated liver enzymes vs 34.2 +/- 2.6 (P less than 0.001) for the participants with normal values at screening and 34.9 +/- 3.1 and 32.8 +/- 2.8 (P = 0.02) respectively at week 8. Males (46 percent) were more likely than females (21 percent) to have elevated aminotransferases. We found no evidence for hepatic disease during the study period. Slightly elevated and fluctuating serum aminotransferases and alkaline phosphatase concentrations are a more frequent finding in healthy obese populations than previously established. In studies of anti-obesity agents investigators should broaden the entry criteria since elevated aminotransferase levels rarely interfere with the safe conduct of clinical trials in obesity.

RCT Entities:   Population Interventions Outcomes