Type 2 diabetes is characterized by insulin resistance and inflammation. HCQ, a commonly used anti-inflammatory drug for rheumatoid arthritis and lupus, is associated with a lower risk of new-onset type 2 diabetes and reports of hypoglycemia in diabetic patients. PIO, an effective 3rd-line agent in patients failing metformin and SUs, has several side effects (e.g., weight gain, fluid retention, fractures) while HCQ has relatively few. We compared 15 patients taking HCQ 400 mg daily with 7 patients taking PIO 45 mg daily, with baseline HbA1c levels of 7.5-11.0% on maximum-tolerated doses of metformin and a SU, in a randomized controlled trial. Glucose control, insulin resistance, and inflammation (highly-sensitive C-reactive protein, hsCRP) were measured at baseline, 2 and 4 months.

         
Results (Mean ± SD) 
Month HbA1c (%) Weight (kg) Homeostasis Model Assessment (HOMA) % Sensitivity hsCRP (mg/L) 
 HCQ PIO HCQ PIO HCQ PIO HCQ PIO 
0 8.6 ± 1.0 9.1 ± 0.7 85.7 ± 14.3 83.7 ± 18.2 109 ± 97 102 ± 87 6.2 ± 6.7 8.8 ± 7.2 
2 7.5 ± 0.9 6.8 ± 0.3 85.4 ± 13.9 86.2 ± 17.4 85 ± 61 170 ± 138 5.5 ± 5.9 2.2 ± 2.0 
4 7.4 ± 0.9 6.3 ± 0.2 85.4 ± 14.5 87.0 ± 17.9 96 ± 74 180 ± 136 4.2 ± 3.8 3.3 ± 3.7 
pa <0.0001 <0.0001 0.76 0.02 0.50 0.06 0.67 0.001 
pb 0.0001 0.004 0.01 0.054 
         
Results (Mean ± SD) 
Month HbA1c (%) Weight (kg) Homeostasis Model Assessment (HOMA) % Sensitivity hsCRP (mg/L) 
 HCQ PIO HCQ PIO HCQ PIO HCQ PIO 
0 8.6 ± 1.0 9.1 ± 0.7 85.7 ± 14.3 83.7 ± 18.2 109 ± 97 102 ± 87 6.2 ± 6.7 8.8 ± 7.2 
2 7.5 ± 0.9 6.8 ± 0.3 85.4 ± 13.9 86.2 ± 17.4 85 ± 61 170 ± 138 5.5 ± 5.9 2.2 ± 2.0 
4 7.4 ± 0.9 6.3 ± 0.2 85.4 ± 14.5 87.0 ± 17.9 96 ± 74 180 ± 136 4.2 ± 3.8 3.3 ± 3.7 
pa <0.0001 <0.0001 0.76 0.02 0.50 0.06 0.67 0.001 
pb 0.0001 0.004 0.01 0.054 
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 a p value for the change from 0 to 4 months by 1-way repeated ANOVA; b p value for the difference between groups by 2-way repeated ANOVA.

Baseline characteristics were not significantly different between groups. Both drugs were well tolerated and significantly improved glucose control; PIO was more effective than HCQ but also caused significantly more weight gain. PIO increased insulin sensitivity while HCQ did not; PIO also significantly decreased hsCRP. HCQ may be beneficial in uncontrolled type 2 diabetic patients as a 3rd-line agent.

Disclosure

S.H. Hsia: Research Support; Self; AstraZeneca, Bayer AG, Bristol-Myers Squibb Company, Cirius Therapeutics, Eli Lilly and Company, Intarcia Therapeutics, Inc., Ionis Pharmaceuticals, Inc., Ligand Pharmaceuticals, Inc., Merck & Co., Inc., National Institute of General Medical Sciences, PhaseBio Pharmaceuticals, Inc., Sanofi-Aventis, TaiwanJ Pharmaceuticals Co., Ltd., Theracos, Inc., Tobira Therapeutics, VTV Therapeutics. P. Duran: None. M.B. Davidson: Employee; Self; Insulin Algorithms, Inc.

© 2018 by the American Diabetes Association.
2018
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