Main content area

BZ043, a novel long-acting amylin analog, reduces gastric emptying, food intake, glycemia and insulin requirement in streptozotocin-induced diabetic rats

Nascimento, Caio Victor M.F., Sinezia, Celimar, Sisnande, Thayna, Lima, Luís Maurício T.R., Lacativa, Paulo G.S.
Peptides 2019 v.114 pp. 44-49
animal disease models, blood glucose, diabetes mellitus, drugs, food intake, gastric emptying, glucose, glycemic effect, humans, insulin, rats, therapeutics
Amylin analogs are important adjunctive drugs in the treatment of diabetes mellitus. However, a dual therapy with insulin involves inconvenient multiple injections. Here we describe a novel n-terminal PEGylated human amylin analog – BZ043 – and its potential to improve the control of glycemia using lower doses of insulin. The effect of BZ043 over the insulin-mediated control of fed-glycemia was investigated in rats with streptozotocin-induced diabetes treated with the basal analog glargine (GLAR). Fasted rats (3 h) received a single treatment of BZ043 (16, 64 or 128 nmol/kg), GLAR (1.5 IU or 6.0 IU) or BZ043 plus GLAR low dose (1.5 IU) in separate injections, and had free access to 5% glucose rich chow and water. BZ043 dose-proportionally prevented the meal-related increase of glycemia, and the co-treatment (64 or 128 nmol/kg) with GLAR restored normoglycemia without abrupt variations of glycemia. BZ043 showed a prolonged anti-hyperglycemic effect and, together with GLAR, promoted a long-lasting normoglycemia, in vivo. We conceive that combining BZ043 and GLAR in a fixed-ratio co-formulation might conveniently improve the control of diabetes mellitus.