Effects of the thyromimetic agent diiodothyropropionic acid on body weight, body mass index, and serum lipoproteins: a pilot prospective, randomized, controlled study.
BACKGROUND
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.


METHODS
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 T(3) and T(4), but there were no differences in clinical manifestations of thyrotoxicosis or hypothyroidism. Serum total and low-density lipoprotein cholesterol levels both decreased on DITPA; there was a transient decrease in triglycerides and no change 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.


CONCLUSIONS
This investigation of DITPA actions demonstrated its efficacy in reducing body weight and lowering total and low-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.
Ladenson
P W
PW
Department of Endocrinology and Metabolism, John Hopkins University, 1830 East Monument Street, Suite 333, Baltimore, Maryland 21287-0003, USA. ladenson@jhmi.edu
McCarren
M
M
Morkin
E
E
Edson
R G
RG
Shih
Mei-Chiung
MC
Warren
S R
SR
Barnhill
J G
JG
Churby
L
L
Thai
H
H
O'Brien
T
T
Anand
I
I
Warner
A
A
Hattler
B
B
Dunlap
M
M
Erikson
J
J
Goldman
S
S
D000368:Aged; D015992:Body Mass Index; D001835:Body Weight / Q000187:drug effects*; D002908:Chronic Disease; D004104:Diiodothyronines / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D008074:Lipoproteins / Q000097:blood*; D008875:Middle Aged; D010012:Osteogenesis / Q000187:drug effects; D018579:Patient Selection; D010865:Pilot Projects; D011422:Propionates / Q000494:pharmacology* / Q000627:therapeutic use; D011446:Prospective Studies; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D013997:Time Factors; D016896:Treatment Outcome; D014284:Triiodothyronine / Q000097:blood
D004104:Diiodothyronines; D008074:Lipoproteins; D011422:Propionates; D014284:Triiodothyronine; C082182:3,5-diiodothyropropionic acid; D013972:Thyrotropin; D013974:Thyroxine