Table 2.

Role of drugs in lipid disorders and diabetes to counteract cancer.

Drug Category	Type of Drug	Mechanisms	Role in Cancer
Antihyperglycemic agents	Metformin	Downregulates insulin/IGF-1 through AMPK Inhibits cancer cell proliferation by mTORC1 inhibition Regulates oncogenes and tumor suppressor genes Targets ROS Prevents lipotoxicity and the pathological browning of WAT Ligand RAGE inhibitor	Beneficial effect
	GLP-1 agonists, liraglutide as example	Cardiovascular protective actions Could preserve endothelial barrier integrity by reversing oxLDL-induced endothelial permeability	Has not been found to significantly modify cancer risk
	DPP-4		Neutral effect on overall cancer risk; may even be beneficial in colorectal cancer—significantly reduced risk
	SGLT-2		Unclear whether it possesses anticancer potential or if it is potentially harmful May raise risk of bladder cancer and reduce risk of gastrointestinal cancer
	Insulin and insulin analogs		Associated with a significant increase in total cancer risk by almost 50% compared to other antihyperglycemic drugs
Hypolipidemic agents	Statins	Inhibit HMG-CoA reductase, involved in cholesterol biosynthesis, and inhibit the mevalonate pathway Antioxidant effects by modulating NRF2/HO-1 Block the proliferation of cancer cells by inhibiting PI3K-Akt Inhibit cancer cell growth by inducing apoptosis mediated through inhibition of GTP Inhibit the mevalonate pathway Possibly induce cancer cell death, although this still remains unclear	May inhibit cancer cell growth Lipophilic statins have better anticancer activities
	Ezetimibe	Inhibits intestinal sterol absorption by directly targeting NPC1L1	Ezetimibe reduced breast tumor size and proliferation in mice NPC1L1 can serve as an independent prognostic marker for colorectal cancer
	PCSK9 inhibitors	induce cancer cell apoptosis	Poor data on effectiveness and safety of PCSK9 inhibitors in cancer still unknown role PCSK9 siRNA may suppress the proliferation and invasion of several tumors
Specific drug targets of lipid metabolism	FASN inhibitors (FASNi)	Target FFA metabolism FASNi platensimycin has anti-diabetic effect and potential in diabetes-associated breast cancer, especially against the HER2+ subtype	Unexpected adverse events
	SCD1 inhibitors	Suppress proliferation and induce apoptosis in a number of cancer cell types	Have remained at a pre-clinical level
	LXRs agonists		Strong anti-tumor response in mice The development of new effective treatments is hampered because LXRs induce SCD1 and fatty acid synthesis
	NRF2 inhibitors	Maintaining a normal redox state can have a detrimental impact on cancer treatment	Still under investigation

Note: IGF-1, insulin-like growth factor-1; RAGE, Receptor for advanced glycation end products (AGEs); WAT, white adipose tissue; GLP-1, glucagon-like peptide-1 agonists; DPP-4, dipeptidyl peptidase-4 inhibitors; SGLT-2, inhibitors of sodium glucose cotransporter-2; HMG-CoA, β-Hydroxy-β-methylglutaryl-CoA reductase; GTP, small guanine triphosphate-binding proteins; NRF2/HO-1, nuclear factor erythroid 2-related factor 2/heme oxygenase-1; NPC1L1, Niemann-Pick C1-like 1; other abbreviations are mentioned in Table 1.