Context: Widespread thyroid hormone actions offer the possibility of developing selective thyromimetic analogs with salutary metabolic properties. Consequently, effects of diiodothyropropionic acid (DITPA) on body weight, serum lipoproteins, and bone metabolism markers were studied in a prospective, controlled, double-blind 24-wk trial, which was primarily designed to assess treatment of stable chronic heart failure. Design: Eighty-six patients (aged 66 ± 11 yr, mean ± SD) were randomized (1:2) to placebo or an escalating DITPA dose (90 to 180, 270, and 360 mg/d) over 8 wk until serum TSH was less than 0.02 mU/liter. Patients were studied at 2, 4, 6, 8, 16, and 24 wk and after 4 wk off study drug. Only 21 DITPA-treated and 27 placebo patients completed the full 24 wk of therapy. Results: DITPA therapy lowered serum TSH levels and, to a lesser extent, serum T3 and T4, buttherewere no differences in clinical manifestations of thyrotoxicosis or hypothyroidism. Serum total and lowdensity lipoprotein cholesterol levels both decreased on DITPA; there was a transient decrease in triglycerides andnochange in high-density lipoprotein cholesterol. DITPA therapy was associated with significant reduction in body weight, 12.5 lb at 24 wk. Increases in serum osteocalcin, N-telopeptide, and deoxypyridinoline levels were consistent with increased bone turnover on DITPA. Conclusion: This investigation of DITPA actions demonstrated its efficacy in reducing body weight andlowering totalandlow-density lipoprotein cholesterol levels. However, DITPA's adverse effects at doses used resulted in a high dropout rate and potentially dangerous skeletal actions were observed.