BM 17.0744 (2,2-dichloro-12-(p-chlorophenyl)-dodecanoic acid) is a substance from a group of omega-substituted alkyl
carboxylic acids with the general formula, ring-spacer-
carboxylic acid. With BM 17.0744-a compound structurally unrelated to
thiazolidinediones--
antihyperglycemic and antihyperinsulinemic potency has been demonstrated in various animal models of type II diabetes. The
antidiabetic effect is independent of the genetic background of the disease, gender, and animal species. The 24-hour
blood glucose profile was dose- and time-dependently improved in ob/ob mice after a single and fourth
oral administration of 0.3, 1, and 3 mg/kg/d. A dose-dependent reduction of
hyperglycemia (10%, 15%, 28%, and 66%) was found in db/db mice after the fifth
oral administration of 3, 10, 30, and 100 mg/kg/d.
Hyperinsulinemia was reduced dose-dependently in yellow KK mice by 1%, 24%, 34%, and 66% after the fifth
oral administration of 0.3, 1, 3, and 10 mg/kg/d. Overall
glucose metabolism was predominantly higher in euglycemic-hyperinsulinemic clamp studies in obese fa/fa rats pretreated for 14 days with 10 mg/kg/d
BM 17.0744. The data in diabetic and
insulin-resistant animals suggest an improvement of
insulin action that is supported by enhancement of
insulin effects in vitro. There is no evidence of a risk for
hypoglycemia in diabetic and metabolically healthy animals.
Triglyceride (TG) and
cholesterol were reduced in the serum of metabolically healthy rats, as well as serum
lipids in db/db mice, which suggests this effect is independent of amelioration of the diabetic status.
Lipid-lowering effects in diabetic and healthy animals show an additional property of
BM 17.0744. Because of its
antidiabetic and
lipid-lowering potency, the substance is of great interest in treating the
metabolic syndrome.
Lipid decreases in rats are associated with a dose-dependent increase in
carnitine acetyltransferase activity in the liver to about 100-fold (12.5 mg/kg/d). This together with
hepatomegaly in small rodents may indicate peroxisomal proliferation, a phenomenon considered species-specific. Its relevance for humans is well documented for other classes of compounds including
fibrates. Specific side effects of
insulin sensitizers of the
thiazolidinedione type, such as an increase in
body weight and heart weight, could not be observed after 4-week oral application of
BM 17.0744 in rats. In general,
BM 17.0744 was well tolerated in the pharmacological dose range in all species tested.