Efficacy and safety of hydroxychloroquine in the treatment of type 2 diabetes mellitus: a double blind, randomized comparison with pioglitazone

Abstract

Objective:

To compare efficacy and safety of hydroxychloroquine with pioglitazone in type 2 diabetes mellitus (T2DM).

Research design and methods:

This double-blind study randomized 267 uncontrolled type 2 diabetes patients (HbA1c ≥7.5% and ≤11.5%), post 3 months’ treatment with glimepiride/gliclazide and metformin, to additionally receive hydroxychloroquine 400 mg/day (n = 135) or pioglitazone 15 mg/day (n = 132) for 24 weeks. Efficacy was assessed by changes in HbA1c, fasting (FBG) and post-prandial (PPG) blood glucose at Week 12 and Week 24.

Results:

At Week 12 and Week 24, HbA1c, FBG and PPG significantly reduced from baseline in both groups. Mean reduction in glycemic parameters at Week 12 (HbA1c: −0.56% vs −0.72%, p = 0.394; FBG: −0.99 mmol/L vs −1.05 mmol/L, p = 0.878; PPG: −1.93 mmol/L vs −1.52 mmol/L, p = 0.423) and Week 24 (HbA1c: −0.87% vs −0.90%, p = 0.909; FBG: −0.79 mmol/L vs −1.02 mmol/L, p = 0.648; PPG: −1.77 mmol/L vs −1.36 mmol/L, p = 0.415) was not significantly different between the hydroxychloroquine and pioglitazone groups. Change in total cholesterol (TC) and LDL-C was significant in favor of hydroxychloroquine (TC: −0.37 mmol/L vs 0.03 mmol/L, p = 0.002; LDL-C: −0.23 mmol/L vs 0.09 mmol/L, p = 0.003). Triglycerides significantly reduced in both groups at Week 24. Mean HDL-C remained unchanged. Study treatments were well tolerated.

Conclusion:

With favorable effects on glycemic parameters and lipids, hydroxychloroquine may emerge as well tolerated therapeutic option for T2DM.

Limitations:

The sample size for this study was small. However, based on the encouraging results of this proof-of-concept study, longer duration studies in larger population can be conducted to further confirm these findings.

Trial registration details:

Clinical Trial Registry–India URL: http://ctri.nic.in, Registration Number: CTRI/2009/091/001036.

Keywords::

• Hydroxychloroquine
• Metformin
• Pioglitazone
• Sulfonylurea
• Type 2 diabetes mellitus

Transparency

Declaration of funding

The study was sponsored by Ipca Laboratories Limited.

A.P. and N.B.C. were involved in conceptualization, coordination, and execution of study at all centers. Study investigators were: N.T. at the Department of Endocrinology, Diabetes, and Metabolism, Christian Medical College, Vellore, India; V.V. at the MV Hospital for Diabetes and Diabetes Research Centre, Chennai, India; A.D. at the Department of Medicine, Grant Medical College and Sir JJ Group of Hospitals, Mumbai, India; O.P.G. at the Department of Medicine, MG Institute of Medical Sciences, Sewagram, India; A.S. at the Department of Medicine, BJ Medical College and Civil Hospital, Ahmadabad, India; A.K. at the Department of Medicine, Padmashree; Dr D.Y. Patil, Medical College and Hospital, Pimpri, India; S.B. at the Bhandari Clinic and Research Centre, Jaipur, India; N.K.T., Department of Medicine, Calicut Medical College and Hospital, Calicut, India; B.S. at Diacare-A Complete Diabetes Care and Hormone Clinic, Ahmadabad, India; S.D. at the Department of Medicine, Shri BM Patil Medical College, Bijapur, India; N.B.V. at the Department of Medicine, Andhra Medical College and KG Hospital, Visakhapatnam, India; S.S. at the Department of Medicine, SMS Medical College and Hospital, Jaipur, India; N.A. at the Diabetes, Obesity, and Thyroid Centre, Gwalior, India; M.M. at the Department of Medicine, JSS Medical College and Hospital, Mysore, India; and K.K. at the Department of Medicine, MGM College and Hospital, Jaipur, India. These authors were involved in generating data at their respective sites, all the investigators played a vital role throughout the conduct of this study and they have also approved the final version of the article to be published.

Declaration of financial/other relationships

A.P. and N.B.C. have disclosed that they are employees of Ipca Laboratories Limited. N.T., V.V., A.D., O.P.G., A.S., A.K., S.B., N.K.T., B.S., S.D., N.B.V., S.S., N.A., M.M., and K.K. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

The authors acknowledge Dr Vishakha Jain, who was a study co-investigator at Mahatma Gandhi Institute of Medical Sciences, Sewagram, India. The authors would also like to acknowledge the efforts of Ravikiran Payghan and Neha Magar, employees of Ipca Laboratories Limited, for their support in coordinating the study related activities at all the sites; Kumar Naidu, Suresh Padwal, and Uma Sargar, employees of Ipca Laboratories Limited, for statistical analysis and data management for this study; Shruti Kulkarni and Pankaj Wadibhasme, employees of Ipca Laboratories Limited, for their help in drafting this manuscript; and Tushar Jadhao, employee of Ipca Laboratories Limited, for his help in labeling and packaging of clinical trial supplies.