Targeting adipose remodeling: Synergistic mechanisms of drugs and adipose-derived stem cells in obese type 2 diabetes mellitus

Table 7 Mapping of combined therapy components to targeted complication pathways and endpoints

Combination	Dominant mechanism (within unified axis)	Target complication	Key endpoints	Notes
GLP-1RA + ADSC/EV	Reducing adipose inflammation → improved endothelial function; proangiogenic repair	ASCVD	MACE, FMD, hs-CRP	Weight loss enables ADSC efficacy
SGLT-2i + ADSC/EV	Hemodynamic unloading; anti-fibrosis + tubular regeneration	HF/CKD	HF hospitalization, eGFR slope, UACR	Monitor volume status
Metformin + ADSC/EV	AMPK activation; mitochondrial support + neurotrophic cues	Neuropathy	NCS, QST, CCM metrics	Consider B12 monitoring
Low-dose PPARγ + ADSC/EV	Adipose remodeling; anti-inflammation + anti-fibrosis	Multiorgan	Composite renal/cardiac endpoints	Consider edema risk

GLP-1RA: Glucagon-like peptide-1 receptor agonist; ADSC: Adipose-derived stem cell; EV: Extracellular vesicle; SGLT-2i: Sodium-glucose cotransporter-2 inhibitor; PPARγ: Peroxisome proliferator-activated receptor gamma; AMPK: Adenosine monophosphate-activated protein kinase; ASCVD: Atherosclerotic cardiovascular disease; HF: Heart failure; CKD: Chronic kidney disease; MACE: Major adverse cardiovascular events; FMD: Flow-mediated dilation; hs-CRP: High-sensitivity C-reactive protein; eGFR: Estimated glomerular filtration rate; UACR: Urinary albumin-to-creatinine ratio; NCS: Nerve conduction study; QST: Quantitative sensory testing; CCM: Corneal confocal microscopy; B12: Vitamin B12.