Old Malaria Drug Effective In Reducing Blood Glucose

The anti-inflammatory drug Hydroxychloroquine shows promise in off label use.

Amit Gupta, MD, of the GD Diabetes Institute, Kolkata, India, presented new research findings on hydroxychloroquine, an older immunosuppressive drug, showing effectiveness in patients with type 2 diabetes at the 2019 Annual Scientific & Clinical Congress hosted by the American Association of Clinical Endocrinologists (AACE). In a study conducted in India, a total of 87 patients proved adding hydroxychloroquine 400 mg to the max doses of their antidiabetic regimen (metformin and vildagliptin) was just as effective in reducing HbA1C as adding canagliflozin 300 mg. The study also showed hydroxychloroquine in association with more weight loss and similar safety profiles compared to canagliflozin.

Hydroxychloroquine is an anti-inflammatory drug; classified as a disease modifying anti-rheumatic drug (DMARD), that suppresses T-cell lymphocyte response. This drug is among the oldest prescribed drugs first used to treat malaria; now it’s being used to treat autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis (RA). Previous studies have shown this drug increases the insulin availability by inhibiting the breakdown of insulin enzymes, which causes glucose levels to reduce. In a small pilot study, the treatment with hydroxychloroquine showed a significant improvement in insulin sensitivity in patients with obesity. In a retrospective study in 2011, 1,127 patients with rheumatoid arthritis using hydroxychloroquine indicated a 71% reduction risk of incident diabetes (hazard ratio 0.29; 95% CI 0.09–0.95; p = 0.04). In a similar retrospective study, 13,905 patients recently diagnosed with RA or psoriasis using hydroxychloroquine showed greater benefit in reducing the occurrence of diabetes than any other DMARDs (hazard ratio 0.54; 95% CI 0.36–0.80).

During the 2019 Annual Scientific & Clinical Congress, Gupta explained how hydroxychloroquine has been approved in India since 2014 as an add-on (with two other anti-diabetic medications) for patients with type 2 diabetes to help reach and maintain glycemic target goals. Due to previous studies of the favorable glucose lowering effect in use of hydroxychloroquine, Gupta discussed why using this drug could be an alternate to canagliflozin, because of the latter’s high cost.

Gupta summarized a 24-week study involving 87 patients with type 2 diabetes using both max doses of metformin and vildagliptin (dipeptidyl peptidase-4 inhibitor) with initiating hydroxychloroquine instead of canagliflozin, a sodium- glucose cotransporter type 2 inhibitor. The primary outcome of this study was to show the effects of hydroxy quinine in combination with the other anti-diabetic drugs (metformin and vildagliptin) on lowering the patient’s HbA1C compared to those who used canagliflozin. The average duration of the study was 6.1 years, with patients’ average mean of HbA1C being 8.4%. Patients were randomized for the choice of hydroxychloroquine 400 mg or canagliflozin 300 mg daily, as add-on therapy. The standard max doses of metformin and vildagliptin were 2000 mg and 100 mg daily, respectively. The primary outcome was hydroxychloroquine lowered HbA1C from baseline of 8.32% to 7.11% (P= .001) and from 8.63% to 7.44% with canagliflozin (P=.001). Due to insignificant decrease between the two groups, hydroxychloroquine decreased HbA1C just the same as canagliflozin.

Effects of fasting plasma glucose with hydroxychloroquine and canagliflozin were lowered from 143 to 112 mg/dL (P=0.001) and 147 to 117 mg/dL (P=0.001), respectively (P= 0.31 between both groups). Post prandial levels were reduced 210 to 142 mg/dL (P = .001) and 219 to 153 mg/dL (P = .001), respectively (P = .05 between groups). The hydroxychloroquine group also saw a decrease in body mass index (from 27.2 to 25.7 kg/m2; P = .003), with canagliflozin being unaffected. Gupta and the medical experts in attendance were surprised by the weight loss, noting that canagliflozin has shown reports of increased appetite.

Gupta summarized current and past studies as hydroxychloroquine emerging into a dual action drug as lowering glucose levels and having anti-inflammatory properties. Gupta further stated that the advanced, modern diabetic treatment has moved beyond glucose control; it’s now in connection to diabetes, obesity, and cardiovascular mortality and morbidity. Session moderator Lance Sloan, MD, medical director of the Texas Institute for Kidney and Endocrine Disorders, Lufkin, Texas, questioned the data regarding cardiovascular mortality and morbidity. Slogan stated that he would consider hydroxychloroquine if cost was an issue, but he needs more information to support cardiovascular evidence. Although hydroxychloroquine seems to be a safe and cost-effective drug, more cardiovascular and renal evidence has to be studied.

Practice Pearls:

• The study concluded that 400 mg of hydroxychloroquine reduced the patients’ HbA1C equivalently to 300 mg of canagliflozin.
• Clinicians should be aware of the potential hypoglycemic effect of antimalarials such as hydroxychloroquine, which can be used as an additional agent to anti-diabetic regimens.
• Hydroxychloroquine is not approved in the U.S. for treatment of diabetes.

References:

1.     Hage, Mirella P, et al. “A Favorable Effect of Hydroxychloroquine on Glucose and Lipid Metabolism beyond Its Anti-Inflammatory Role.” Therapeutic Advances in Endocrinology and Metabolism, SAGE Publications, Aug. 2014, www.ncbi.nlm.nih.gov/pmc/articles/PMC4206615/.
2. “Old Malaria Drug as Good as Blockbuster Type 2 Diabetes Agent.” Medscape, 3 May 2019, www.medscape.com/viewarticle/912548#vp_1.

Emma Kammerer, L|E|C|O|M Bradenton School of Pharmacy, PharmD Candidate