What does this research mean for the field?

Oral pretreatment with metformin, dapagliflozin, or their combination preserved body weight and normalized cardiometabolic parameters in doxorubicin/cisplatin-intoxicated rats. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

The research aims to evaluate the protective effects of metformin, dapagliflozin, and their combination on cardiometabolic disruptions caused by doxorubicin and cisplatin.

February 8, 2026Open Access

Mitigating Doxorubicin- and Cisplatin-Induced Cardio-Metabolic Disruptions: The Differential Pharmacological Modulatory Role of Metformin, Dapagliflozin, and a Fixed-Dose Combination on Metabolic Profile in Wistar Rats

Key Result

Oral pretreatment with metformin, dapagliflozin, their combination, or silymarin significantly preserved body weight and normalized cardiometabolic parameters in DOX/CIS-intoxicated rats.

Key Points

The research aims to evaluate the protective effects of metformin, dapagliflozin, and their combination on cardiometabolic disruptions caused by doxorubicin and cisplatin.
Conducted on male Wistar rats weighing 130-190 g, aged 10-12 weeks.
Rats were pretreated for 14 days with metformin, dapagliflozin, a combination of both, or silymarin.
Doxorubicin and cisplatin were administered on alternate days from day 4 to 14.
Cardiometabolic profiles were assessed by measuring body weight, fasting blood glucose, and serum lipid profile.
Doxorubicin and cisplatin led to significant body weight loss and altered fasting blood glucose and lipid levels.
Pretreatment with metformin, dapagliflozin, and the combination resulted in significant preservation of body weight.
Normalization of fasting blood glucose and improvement of lipid parameters were observed in treated groups.

Structured PICO

Does pretreatment with metformin, dapagliflozin, or their combination prevent doxorubicin- and cisplatin-induced cardiometabolic disruptions in Wistar rats?

Population

Male Wistar rats (weight: 130-190 g; age: 10-12 weeks) intoxicated with a combination of doxorubicin (DOX) and cisplatin (CIS).

Intervention

Oral pretreatment for 14 consecutive days with either metformin (200 mg/kg/day), dapagliflozin (10 mg/kg/day), a metformin-dapagliflozin fixed-dose combination (100 mg/kg/day metformin and 5 mg/kg/day dapagliflozin), or silymarin (20 mg/kg/day). From day 4 to day 14, doxorubicin (2.5 mg/kg) and cisplatin (1.5 mg/kg) were administered on alternate days.

Comparator

DOX/CIS-intoxicated group receiving no protective pretreatment.

Outcome

Cardiometabolic profile assessed by measuring body weight, fasting blood glucose, serum lipid profile, and cardiovascular risk indices.surrogate

Pretreatment with metformin, dapagliflozin, or their combination significantly mitigates doxorubicin- and cisplatin-induced cardiometabolic dysfunction in a rat model.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

The therapeutic efficacy of antineoplastic agents like doxorubicin (DOX) and cisplatin (CIS) is often limited by their significant cardiotoxic and metabolic side effects. This study investigated the protective effects of oral pretreatment with metformin (MET), dapagliflozin (DAP), a MET-DAP fixed-dose combination, and silymarin (SLM) on the cardiometabolic profile of rats intoxicated with a combination of these chemotherapeutic drugs. Male Wistar rats (weight: 130-190 g; age: 10-12 weeks) were pretreated for 14 consecutive days with either 200 mg/kg/day MET, 10 mg/kg/day DAP, a MET-DAP combination (100 mg/kg/day MET and 5 mg/kg/day DAP), or 20 mg/kg/day SLM. From day 4 to day 14, DOX (2.5 mg/kg) and CIS (1.5 mg/kg) were administered on alternate days. The cardiometabolic profile was assessed by measuring body weight, fasting blood glucose, serum lipid profile, and cardiovascular risk indices. The DOX/CIS-intoxicated group exhibited significant reductions in body weight and detrimental alterations in fasting blood glucose and lipid parameters, indicative of severe cardiometabolic dysfunction. Oral pretreatment with MET, DAP, MET-DAP, and SLM effectively counteracted these negative effects, leading to a significant (p≤0.05, p≤0.001, and p≤0.0001) preservation of body weight and normalization of the measured cardiometabolic parameters. These findings suggest that these oral agents possess significant pharmacological activity in mitigating DOX/CIS’ adverse cardiometabolic effects. Thus, highlighted the promising adjunctive therapy of MET-DAP combination in improving patient outcomes during chemotherapy.