Efficacy of Metformin Course Application Combined with Intranasal Insulin in Treating Rats with Cafeteria Diet-Induced Obesity

The so-called cafeteria diet (CD), rich in saturated fatsand light fast-digesting carbohydrates, leads to obesity and isa risk factor for type 2 diabetes. Metformin (MF) is often usedto correct diet-induced obesity, but in some patients, it elicitsserious side effects, which requires dose reduction, including throughits co-application with drugs potentiating MF effects. Intranasallyadministered insulin (INI), which perse has a restorative potential in the treatment of metabolicdisorders, is a candidate for the role of such a drug. This workwas aimed to study the efficacy of a 3-week combined course of MF(100 mg/kg/day, perorally) and INI (1.5 or 6.0 IU/kg/day) to correctmetabolic and hormonal disorders in male rats with CD-induced obesity(CDIO). It was shown that in CDIO rats, the MF + INI combination normalizedbody weight and abdominal fat, as well as restored glucose homeostasis,lipid metabolism, basal and glucose-stimulated insulin and leptinlevels. Compared to MF monotherapy, a combined course of MF + INIapplication more effectively restored insulin sensitivity, as assessedby a decrease in the insulin resistance index, and normalized glucosetolerance, as assessed by a decrease in AUC_0–120, theintegrated area under glucose concentration curves in the glucosetolerance test. The combination of MF with INI at a dose of 1.5IU/kg/day normalized thyroidal status, disturbed in CDIO, whilethe combination of MF with INI at a dose of 6 IU/kg/day exacerbatedthe hypothyroid state, mainly due to hyperactivation of thyroid-stimulatinghormone secretion and the development of thyroid resistance to thishormone. Thus, a combined course of MF with relatively low-doseINI, which has no negative effects on the thyroid axis, appearspromising for correcting metabolic and hormonal indices in CDIO, includingfunctional restoration of the thyroid system.