Potential Effect of Hydroxychloroquine in Diabetes Mellitus: A Systematic Review on Preclinical and Clinical Trial Studies

Table 2

Effect of hydroxychloroquine against diabetes mellitus on different animal models.

Experimental model	Method and intervention	Treatment outcome	References
Alloxan-induced diabetic rats	Alloxan- (120 mg/kg) induced 42 diabetic rats were randomly allocated to seven groups taking metformin 850 mg/70 kg body weight (BW)/day, glibenclamide at 10 mg/70 kg BW/day, HCQ 300 mg/70 kg BW/day, individually for 2 weeks and metformin 850 mg/70 kg BW/day, glibenclamide 10 mg/70 kg BW/day, HCQ 300 mg/70 kg BW/day, combination therapy, metformin with HCQ () and glibenclamide with HCQ (), respectively, for 4 weeks.	Combination of HCQ with metformin and glibenclamide significantly reduced blood glucose level than individual therapy. In addition, increment in liver glycogen levels was observed. Further improvement in the lipid profile was observed in combination therapy.	[27]
Chow and HFD-received Sprague Dawley rats	54 rats were randomly divided into three groups (): group I: control group; group II: high-fat diet (HFD) group; and group III: HCQ+HFD group. Taking 6.5 mg/kg/d orally of HCQ 200 mg tablet for 12 weeks.	Mild degenerative change in the islet of Langerhans (IOL) was seen in the HFD group, and it was preserved in the HCQ taking group. Serum levels of FBG, insulin, AUC, HOMA-IR significantly decreased in the HFD+HCQ group compared with those of the HFD group. Adipokines were significantly elevated in the HFD groups.	[28]
Adult male mice	76 mice were randomly assigned into four groups (/group): group I, control vehicle (0.5% hydroxypropyl methylcellulose and 1% Tween 80 in sterile water); group II, TAD, 6 mg/kg daily mixed in-vehicle solvent; group III, HCQ 50 mg/kg daily mixed in-vehicle solvent; and group IV, Tadalafil (TAD) (6 mg/kg daily) 1 HCQ (50 mg/kg daily) mixed in-vehicle solvent.	The plasma level of insulin was increased, and the plasma level of glucose was decreased in the HCQ and TAD±HCQ groups. Plasma levels of free fatty acids and triglycerides were significantly decreased in the TAD±HCQ group. TAD±HCQ improved insulin TAD, HCQ, and TAD±HCQ treated animals had a clear trend toward increased pancreas mass/body weight. The mammalian target of rapamycin complex 2 was dramatically increased in the HCQ and TAD±HCQ treatment groups.	[29]

AUC: area under the curve; BW: body weight; HCQ: hydroxychloroquine; HFD: high-fat diet; HOMA-IR: homeostatic model assessment-insulin resistance; IOL: the islet of Langerhans; TAD: Tadalafil.