Abstract

Obesity and type 2 diabetes frequently coexist as “diabesity,” a chronic condition driven by insulin resistance, β
cell stress, lipotoxicity, oxidative damage, and metaflammation. Conventional monotherapies that focus on 
single pathways often produce incomplete or transient benefits, especially in individuals with severe obesity, 
fatty liver disease and complex cardiovascular risk. Combination regimens that integrate antioxidants, bioactive 
peptides and metabolic hormones are conceptually attractive because they can simultaneously target redox 
stress, appetite and energy homeostasis, glucose control and organ protection. However, co-administration of 
multiple agents in free form is hampered by mismatched pharmacokinetics, off-target toxicity and adherence 
challenges. Nanotechnology offers a means to co-encapsulate and coordinate these agents within a single 
platform, enabling synchronized delivery, tissue targeting and controlled release. Nano-enabled combination 
systems can, in principle, protect labile antioxidants, stabilize peptides and hormones, tune their exposure 
profiles and direct them toward key metabolic organs such as adipose tissue, liver, skeletal muscle and pancreatic 
islets. This review discusses the rationale for combining antioxidants, peptides and hormones in diabesity; 
describes nanocarrier platforms suitable for their co-delivery; and examines how redox modulation, peptide 
signaling and endocrine control can be integrated at the nanoscale. Preclinical examples are highlighted 
alongside safety, manufacturing and regulatory considerations. Finally, the article outlines future directions, 
including stimulus-responsive and patient-tailored nanoformulations that complement lifestyle change and 
emerging incretin therapies in the personalized management of diabesity.