The combined effect of metformin and mirabegron on diet-induced obesity

Xin Yuan Zhao, Ying Liu, Xuan Zhang, Ben Chi Zhao, George Burley, Zhi Can Yang, Yi Luo, An Qi Li, Ruo Xin Zhang, Zhi Ying Liu, Yan Chuan Shi, Qiao Ping Wang

Research output: Contribution to journalArticlepeer-review


Anti-obesity medications act by suppressing energy intake (EI), promoting energy expenditure (EE), or both. Metformin (Met) and mirabegron (Mir) cause weight loss by targeting EI and EE, respectively. However, anti-obesity effects during concurrent use of both have yet to be explored. In this study, we investigated the anti-obesity effects, metabolic benefits, and underlying mechanisms of Met/Mir combination therapy in two clinically relevant contexts: the prevention model and the treatment model. In the prevention model, Met/Mir caused further 12% and 14% reductions in body weight (BW) gain induced by a high-fat diet compared to Met or Mir alone, respectively. In the treatment model, Met/Mir additively promoted 17% BW loss in diet-induced obese mice, which was 13% and 6% greater than Met and Mir alone, respectively. Additionally, Met/Mir improved glucose tolerance and insulin sensitivity. These benefits of Met/Mir were associated with increased EE, activated brown adipose tissue thermogenesis, and white adipose tissue browning. Significantly, Met/Mir did not cause cardiovascular dysfunction in either model. Together, the combination of Met and Mir could be a promising approach for the prevention and treatment of obesity by targeting both EI and EE simultaneously.

Original languageEnglish (US)
Article numbere207
Issue number2
StatePublished - Apr 2023
Externally publishedYes


  • combination therapy for obesity
  • energy expenditure
  • food intake
  • metformin
  • thermogenesis
  • β3-adrenergic receptor agonist

ASJC Scopus subject areas

  • Drug Discovery
  • Genetics(clinical)
  • Biochemistry, medical
  • Genetics
  • Oncology
  • Immunology and Allergy
  • Computer Science Applications
  • Cell Biology


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