Empagliflozin Effectively Attenuates Olanzapine-Induced Body Weight Gain in Female Wistar Rats

Abstract

Atypical antipsychotic drugs are commonly associated with undesirable side effects including body weight gain (BWG) and metabolic deficits. Many pharmacological interventions have been tested in an attempt to minimize or prevent these side effects. Preliminary evidence suggests that antidiabetic drugs may be effective in attenuating antipsychotic-induced BWG. In the current study, we examined the effect of an antidiabetic drug empagliflozin (EMPA) on BWG induced by anatypical antipsychotic drug olanzapine (Ola) in female and male Wistar rats. Rats were divided into six groups based on the dose they received: group 1 (female control), group 2 (female EMPA, 20 mg/kg; IG), group 3 (female Ola, 4 mg/kg; IP), group 4 (female Ola, 4 mg/kg; IP + EMPA, 20 mg/kg; IG), group 5 (male control), and group 6 (male Ola, 4 mg/kg; IP). Ola induced sustained increase in BWG. The subsequent treatment of Group 3 and 4 with EMPA attenuated the Ola-induced BWG in female Wistar rats. In terms of the gender difference between female and male Wistar rats, the male control group 5 gained more weight throughout the study as compared to the female control group 1. Similarly, the male Ola group 6 gained more weight throughout the study as compared to the female Ola group 3. However, Ola did not cause any weight difference between male rats treated with Ola in comparison with male control group, thus showing a significant gender difference regarding body weight between male and female Wistar rats regardless of Ola administration. In addition, the present findings showed that EMPA effectively attenuates the Ola induced BWG in female Wistar rats. These novel findings should help to better understand the underlying molecular and behavioral mechanisms contributing to the observed increase in body weight after treatment with Ola and other atypical antipsychotic drugs across male and female rats.

Impact of SGLT2 inhibitors on metabolic status in patients with psychiatric disorders undergoing treatment with second‑generation antipsychotics (Review)

“…In the reported preclinical study, researchers evaluated the effects of empagliflozin on body weight gain induced by olanzapine administration in female and male Wistar rats (31). Olanzapine induced a sustained increase in body weight in this population, while the subsequent treatment with empagliflozin attenuated the antipsychotic-induced weight gain only in female rats (31). Clinical guidelines and expert consensus.…”

“…Based on the current literature review, it can be concluded that SGLT2Is may be added to metformin in selected cases of type 2 diabetes mellitus in the context of antipsychotic treatment, as suggested by a clinical guideline and an expert consensus; a case report and a systematic review also support this strategy ( 1 , 32 , 33 , 37 ). Evidence to support the administration of SGLT2Is as second-line treatment in patients with diabetes mellitus who are also treated with olanzapine or clozapine is derived from very limited preclinical ( 31 ) and clinical data ( 37 ). The advantages of SGLTI2s, i.e., the low risk of hypoglycaemia and the associated weight loss properties, may recommend these agents, along with GLP-1RAs and DPP-4Is, as preferred options for second-line therapy in patients with severe mental disorders ( 33 ).…”

The Prevalence of Hyperuricemia and the Association Between Hyperuricemia and Age in Patients with Psychiatric Disorders to a General Hospital: A Cross-Section Study

“… 61 Norepinephrine, epinephrine and catecholamine are hormones that are very important in the regulation of many metabolic processes. These hormones have been shown to play an essential role in the metabolic side effects of antipsychotics, both in human and animal studies, 62 , 63 which revealed a dose-dependent increase in rodent models. 64 The strong affinity of antipsychotics for 5-HT2C and H1 receptors is considered the primary cause of weight gain.…”

Antioxidant Activity and Effectiveness of Fig Extract in Counteracting Carbon Tetrachloride-Induced Oxidative Damage in Rats

“…The body weight of the rats was monitored on a regular and daily basis. It was measured in grams (g), with a Scaltec SBA 52 balance, and the growth rate of the rats from day one was expressed as a percentage and calculated according to the following formula [97]:…”