Efficacy and safety of hydroxychloroquine as add-on therapy in uncontrolled type 2 diabetes patients who were using two oral antidiabetic drugs

Abstract

Objective To evaluate the Safety and Efficacy of Hydroxychloroquine as add-on therapy in uncontrolled type 2 diabetes patients who were using two oral antidiabetic drugs. Materials and methods This was a double blind, placebo controlled, parallel group study in 304 inadequately controlled type 2 diabetes (T2DM) subjects with two oral antidiabetic drugs (glimepiride 4 mg and metformin 500 mg) were randomised to hydroxychloroquine (HCQ) 200 mg, 300 mg, 400 mg once daily (OD) or placebo. Dose of hydroxychloroquine was selected as per body weight of the subject. Primary end point was glycated haemoglobin (HbA1c) change at week 12 from baseline. Secondary endpoint was change in fasting plasma glucose (FPG), post prandial plasma glucose (PPG), body weight and any adverse reaction including no of hypoglycemic events, as well as a change in the percentage of subjects with A1C < 7.0% and > 6.5% after 12 weeks of treatment.. In follow-up of 400 mg once daily was once again divided to 200 mg twice daily (BD) to study the effect on tolerability profile for further 12 weeks. Results Hydroxychloroquine was associated with significant reduction in HbA1c from baseline (7-8.5%) in 12 weeks −0.78%, −0.91% and 1.2% for hydroxychloroquine 200 mg, 300 mg and 400 mg OD, respectively, versus 0.13% with placebo (P < 0.005). FPG and PPG were reduced by −25 to −38 mg/dl and 34-53 mg/dl, respectively. Body weight also reduced in each group of HCQ. Hypoglycemia was reported only with 300 mg (1.2%) and 400 mg (2.1%) group of HCQ. It was observed that patients who complains with mild GI disturbance with HCQ 400 mg glycemic efficacy was maintained with 200 mg BD with significant relief of the symptoms. Conclusion Hydroxychloroquine added to sulphonylurea and metformin, improves glycemic control significantly in T2DM patients. Glycemic effect of different dose of hydroxychloroquine is dose dependent. The safety/tolerability profile of hydroxychloroquine was favourable except GI disturbance which is more frequent with 400 mg. This can be avoided with 200 mg BD without compromise on efficacy. Keywords Hydroxychloroquine • Type 2 diabetes • HbA1c • FPG • PPG Abbreviations T2DM Type 2 diabetes mellitus management HbA1c Glycated haemoglobin FPG Fasting plasma glucose PPG Post prandial plasma glucose HCQ Hydroxychloroquine * A. Nag

COVID-19 and diabetes mellitus: from pathophysiology to clinical management

“…The two main mechanisms of action of hydroxychloroquine are believed to be via its restriction of viral spike protein cleavage at the ACE2 binding site, and its anti-inflammatory and immunomodulatory properties 177 . Hydroxychloroquine also has glucose-lowering efficacy by increasing insulin sensitivity and improving pancreatic β-cell function 178 , which has enabled hydroxychloroquine to be prescribed as an antidiabetic medication in some countries 179 . Therefore, adjustment of pre-existing antidiabetic drugs might be needed to avoid hypoglycaemia in uncommon cases of patients with diabetes mellitus who are taking hydroxychloroquine 180 – 182 .…”

Efficacy and safety of hydroxychloroquine for managing glycemia in type-2 diabetes: A systematic review and meta-analysis

“…Eleven RCTs in people with T2DM which fulfilled all criteria were analyzed in this meta-analysis (eight from India, one each from the USA, Canada, and Italy). [ 15 16 17 18 19 20 21 22 23 24 25 ] The remaining 10 studies were evaluated in detail but were excluded as they did not fulfill the inclusion criteria of this meta-analysis. [ 26 27 28 29 30 31 32 33 34 35 ] One RCT in prediabetes and another RCT focusing on dyslipidemia instead of glycemia were excluded.…”

Diabetes-Modifying Antirheumatic Drugs: The Roles of DMARDs as Glucose-Lowering Agents

“…More recently, Chakravarti and Nag [ 90 ] conducted a double-blind, placebo-controlled, parallel group study to assess the safety and efficacy of HCQ as an add-on therapy in 304 inadequately controlled T2D patients who were on stable combination therapy with glimepiride and metformin. Participants were randomized to a placebo or HCQ 200 mg, 300 mg, or 400 mg once daily.…”

“…Hypoglycemia was reported only in the 300 mg (1.2%) and 400 mg (2.1%) HCQ groups. Overall, the safety and tolerability profile of HCQ was favorable, except for gastrointestinal disturbances which were more frequent with the HCQ dose of 400 mg [ 90 ]. Notwithstanding, a careful risk-benefit assessment of HCQ is always needed for a cautious use of this drug as an antihyperglycemic agent.…”