Table 1.

Summarizes the impact of known mitotoxic agents on insulin sensitivity .

DRUG CLASS	DRUGS	MITOCHONDRIAL EFFECTS	EFFECT ON INSULIN SENSITIVITY	REFERENCE
NRTI’s	Zidovudine	inhibits the polymerase that replicates mtDNA, thus preventing mitochondrial replication.	Decreases insulin sensitivity	(21, 28)
	Stavudine	MtDNA depletion or damage. Mitochondrial toxicity which induces lipodystrophy	Decreases insulin sensitivity	(29, 30)
Statins	Simvastatin	reduce coenzyme Q10 (CoQ10) levels	Decreases insulin sensitivity	(31)
	Pravastatin	Reduces coupling between electron transport chain and oxidative phosphorylation	Impairs insulin signalling and decreases insulin sensitivity	(32, 33)
Antipsychotics	Chlorpromazin	Inhibits ATPase activit	Exacerbates hepatic insulin sensitivity	(34)
	Haloperidol	Increases formation of mitochondrial ROS and mitochondrial mass	Increase insulin secretion	(35–37)
Antidepressants	Amitriptyline	Induces ROS formation	Decreases insulin sensitivity	(38)
	Sertraline	Perturbs mitochondrial membrane and causes swelling	Increases pancreatic insulin secretion	(36)
Chemotherapy agents	Doxorubicin	Increases ROS, mtDNA adduct and iron overload	Impairs systemic insulin sensitivity	(39)
	Cisplatin	Impairs ETC and increase ROS formation.	Impairs insulin secretion.	(38, 40)
	Tamoxifen	Inhibits mitochondrial respiration and elevated mitochondrial lipid peroxidation.	Decreases hepatic insulin sensitivity	(41, 42)
Antibiotic	Clarithromycin	inhibits the mitochondrial protein synthesis	Improves insulin sensitivity	(28, 31)
	Doxycycline	inhibits the mitochondrial protein synthesis	Improve insulin sensitivity	(43, 44)
Antihypertensives	carvedilol	Inhibits mitochondrial oxygen consumption Mild uncoupling of mitochondrial oxidative phosphorylation	Increases insulin sensitivity	(45–47)
	Captopril	Decreases mitochondrial ATP synthase activity	Improves hepatic insulin sensitivity	(48, 49)
Anti-epileptics	Valproic acid	Inhibits the TCA cycle and mitochondrial fatty acid oxidation	Enhances insulin resistance	(50, 51)
	Phenytoin	Inhibits ETC	Inhibits insulin release	(52, 53)
	Carbamazepine	Inhibits mitochondrial respiration.	Improves insulin sensitivity	(52, 54)
Analgesics	Paracetamo	Induce oxidative stress leading to mtDNA depletion or damage	Improves insulin secretion	(55–58)
	Tramadol	Directly inhibits mitochondrial fatty acid oxidation. OXPHOS uncoupling	Enhances hepatic insulin sensitivity	(59–61)
	Diclofenac	Increases mitochondrial oxidative stress	Improves insulin sensitivity	(60–62)
Anticoagulants	Aspirin	Uncouples mitochondrial oxidation.	Improves insulin sensitivity	(63–66)
	Clopidogrel	Decreases mitochondrial membrane potential Increase ROS production	Improves insulin sensitivity	(61)