Objective:
The epidemic of T2DM is rising across the globe. Systemic inflammation plays a
pivotal role in the pathogenesis and complications of T2DM. Combination of two or more oral hypoglycemic
agents (OHA) is widely prescribed in patients with T2DM, however many patients have poor
glycemic control despite receiving combination therapy. The new antidiabetic drugs are relatively
costly or many patients have anxiety over the use of injectable insulin. The objective of this observational
study was to investigate the effectiveness and tolerability of hydroxychloroquine (HCQ) in
T2DM patients uncontrolled on multiple OHA and despite high sugar level not willing to initiate insulin
therapy in a real-world clinical setting.
Methods:
A prospective, investigator-initiated, observational, single-centred study was conducted
where 250 patients (18-65 years) with T2DM for more than 5 years, with uncontrolled glycemia despite
on a combination of multiple OHA, HbA1c between ≥7% and <10.5%, FPG >130 mg/dL or PPG >180
mg/dL and BMI between >25 and <39 kg/m2, were prescribed hydroxychloroquine sulphate 400 mg
once daily for 48 weeks. Percentage of drugs used at the baseline were as follows: metformin 2000 mg
(100%), glimepiride 4 mg (100%), pioglitazone 30 mg (100%), sitagliptin 100 mg (100%), canagliflozin
300 mg (52.4%), empagliflozin 25 mg (22.8%), dapagliflozin 10 mg (17.6%) and voglibose 0.3
mg (62%). Mean change in HbA1c, blood glucose and hs-CRP at baseline, week 12, 24 and 48 were
assessed using the paired t-test.
Results:
After 48 weeks of add-on treatment with HCQ, almost all SGLT-2 inhibitors were withdrawn;
metformin dose was reduced to 1000 mg, glimepiride reduced to 1 mg and sitagliptin reduced to 50 mg
OD. Patients continued to have good glycemic control. HbA1c was reduced from 8.83% to 6.44%. Reduction
in FPG was 40.78% (baseline 177.30 mg/dL) and PPG was reduced by 58.95% (baseline
329.86 mg/dL). Change in mean body weight was -4.66 Kg. The reduction in glycemic parameters and
mean body weight was significant (p < 0.0001). Hs-CRP was significantly reduced from 2.70±1.98
mg/L to 0.71±0.30 mg/L 9 (p < 0.0001). More reduction in glycemic parameters and body weight was
observed among the patients with higher hs-CRP (> 3 mg/L) as compared to patients with baseline hs-
CRP ≤ 3 mg/L. Most common adverse events reported with the drug therapy were GI irritation (3.6%)
and hypoglycemia (2%). None of the patients required medical assistance for hypoglycemia.
Conclusion:
Add-on treatment of HCQ effectively improved glycemic control in T2DM patients uncontrolled
on multiple antidiabetic drugs. By virtue of its antidiabetic and anti-inflammatory properties,
it may emerge as a valuable therapeutic intervention for the patients with T2DM.