Effectiveness of metformin in combination with intranasal insulin for the treatment of metabolic and hormonal disturbances in adult male rats with metabolic syndrome induced by impaired breastfeeding

BACKGROUND: Limiting or temporally stopping breastfeeding can lead to the development of metabolic syndrome in adulthood, which requires the development of approaches for its prevention and correction. One such approach is treatment with metformin or intranasal insulin. Since the targets of these agents differ and may complement each other, it has been suggested that their combined use could be effective. AIM: To study the effect of a four-week co-administration of metformin (orally, 120 mg/kg/day) and intranasal insulin (1.2 IU/kg/day) in male rats with metabolic syndrome, induced by breastfeeding disruption on postnatal days 19–21, on their metabolic and hormonal parameters. MATERIALS AND METHODS: The study treatment was compared with monotherapy using the same drugs. RESULTS: It was found that adult male rats with disrupted breastfeeding developed obesity, dyslipidemia, hyperleptinemia, impaired glucose tolerance, and a reduction in the number of β-cells and the area of pancreatic islets, which are characteristic of metabolic syndrome. Long-term treatment with metformin and its combination with intranasal insulin partially or fully normalized body weight, abdominal fat, and metabolic and hormonal parameters, with the restorative effect of combination treatment on such parameters as body weight, fat mass, glucose tolerance, and blood glycated hemoglobin levels being more pronounced than with metformin alone. CONCLUSIONS: The results of the study support the use of a combination of metformin and intranasal insulin to normalize metabolic and hormonal parameters in metabolic syndrome induced by breastfeeding disruption in early days of life.