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

Author:
Nascimento, Caio Victor M.F., Sinezia, Celimar, Sisnande, Thayna, Lima, Luís Maurício T.R., Lacativa, Paulo G.S.
Source:
Peptides 2019 v.114 pp. 44-49
ISSN:
0196-9781
Subject:
animal disease models, blood glucose, diabetes mellitus, drugs, food intake, gastric emptying, glucose, glycemic effect, humans, insulin, rats, therapeutics
Abstract:
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.
Agid:
6393491