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Current Diabetes Reviews

Editor-in-Chief

ISSN (Print): 1573-3998
ISSN (Online): 1875-6417

Research Article

Real-World Clinical Effectiveness and Tolerability of Hydroxychloroquine 400 Mg in Uncontrolled Type 2 Diabetes Subjects who are not Willing to Initiate Insulin Therapy (HYQ-Real-World Study)

Author(s): Amit Gupta*

Volume 15, Issue 6, 2019

Page: [510 - 519] Pages: 10

DOI: 10.2174/1573399815666190425182008

Price: $65

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Abstract

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Results: After 48 weeks of add-on treatment with HCQ, almost all SGLT-2 inhibitors were withdrawn; metformin dose was reduced to 1000 mg, glimepiride reduced to 1 mg and sitagliptin reduced to 50 mg OD.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.

Keywords: Hydroxychloroquine, insulin therapy, type 2 diabetes, HbA1c, clinical effectiveness, HYQ-real-world study.

[1]
Kaveeshwar SA, Cornwall J. The current state of diabetes mellitus in India. Australas Med J 2014; 7(1): 45-8.
[http://dx.doi.org/10.4066/AMJ.2013.1979]
[2]
Chawla A, Chawla R, Jaggi S. Microvasular and macrovascular complications in diabetes mellitus; Distinct or continuum? Indian J Endocrinol Metab 2016; 20(4): 546-51.
[http://dx.doi.org/10.4103/2230-8210.183480]
[3]
Wang T-Y, Eguale T, Tamblyn R. Guidelines adherence in the treatment of patients with newly diagnosed type 2 diabetes: A historical cohort comparing the use of metformin in Quebec pre-and post-Canadian Diabetes Association guidelines. BMC Health Serv Res 2013; 13: 442.
[http://dx.doi.org/10.1186/1472-6963-13-442]
[4]
Zoungas S, Patel A, Chalmers J, et al. ADVANCE Collaborative Group. Severe hypoglycaemia and risks of vascular events and death. N Engl J Med 2010; 363: 1410-8.
[5]
Nathan DM, Buse JB, Davidson MB, et al. American Diabetes Association. Medical management of hyperglycaemia in type 2 diabetes: A consensus algorithm for the initiation and adjustment of therapy: A consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2009; 32: 193-203.
[6]
Weng J, Li Y, Xu W, Shi L, Zhang Q, Zhu D, et al. Effect of intensive insulin therapy on beta-cell function and glycaemic control in patients with newly diagnosed type 2 diabetes: A multicentre randomised parallel-group trial. Lancet 2008; 371: 1753-60.
[7]
Syed A, Mohd Don Z, Ng CJ, et al. Using a patient decision aid for insulin initiation in patients with type 2 diabetes: A qualitative analysis of doctor–patient conversations in primary care consultations in Malaysia. BMJ Open 2017; 7e014260
[http://dx.doi.org/10.1136/bmjopen-2016-014260]
[8]
Pharmacologic Approaches to Glycaemic Treatment. American Diabetes Association SO Diabetes Care 2017; 40(Suppl. 1): S64-74.
[9]
Raz I. Guideline Approach to Therapy in Patients with Newly Diagnosed Type 2 Diabetes. Diabetes Care 2013; 36(Suppl. 2): S139-44.
[http://dx.doi.org/10.2337/dcS13-2035]
[10]
Wasko MC, Hubert HB, Lingala VB, et al. Hydroxychloroquine and risk of diabetes in patients with rheumatoid arthritis. JAMA 2007; 298: 187-93.
[11]
Emami J, Pasutto F, Mercer JR, Jamali F. Inhibition of insulin metabolism by hydroxychloroquine and its enantiomers in cytosolic fraction of liver homogenates from healthy and diabetic rats. Life Sci 1999; 64: 325-35.
[12]
Mercer E, Rekedal L, Garg R, et al. Hydroxychloroquine improves insulin sensitivity in obese non-diabetic individuals. Arthritis Res Ther 2012; 14: R135.
[13]
Wasko MCM, Hubert HB, Lingala VB, et al. Hydroxychloroquine and risk of diabetes in patients with rheumatoid arthritis. JAMA 2007; 298(2): 187-93.
[14]
Solomon DH, Massarotti E, Garg R, et al. Association between disease modifying anti-rheumatic drugs and diabetes risk in patients with rheumatoid arthritis and psoriasis. JAMA 2011; 305(24): 2525-31.
[15]
Bili A, Sartorius JA, Kirchner HL, et al. Hydroxychloroquine use and decreased risk of diabetes in rheumatoid arthritis patients. J Clin Rheumatol 2011; 17: 115-20.
[16]
Chen YM, Lin CH, Lan TH, et al. Hydroxychloroquine reduces risk of incident diabetes mellitus in lupus patients in a dose dependent manner: a population-based cohort study. Rheumatology (Oxford) 2015.Jan 12. pii keu451 [Epub ahead of print].
[17]
Quatraro A, Consoli G, Magno M, et al. Hydroxychloroquine in decompensated, treatment-refractory noninsulin-dependent diabetes mellitus. Annals of Internal Med 1990; 112: 678-81.
[18]
Gerstein H, Thorpe K, Taylor D, et al. The effectiveness of hydroxychloroquine in patients with type 2 diabetes mellitus who are refractory to sulfonylureas - a randomized trial. Diabetes Res Clin Pract 2002; 55: 209-19.
[19]
Rekedal LR, Massarotti E, Garg R, et al. Changes in Glycated Hemoglobin after Initiation of Hydroxychloroquine or Methotrexate in Diabetic Patients with Rheumatologic Diseases. Arthritis Rheum 2010; 62(12): 3569-73.
[20]
Pareek A, Chandurkar N, Thomas N, et al. Efficacy and safety of hydroxychloroquine in the treatment of type 2 diabetes mellitus: a double blind, randomized comparison with pioglitazone. Curr Med Res Opin 2014; 30(7): 1257-66.
[21]
Chen L, Magliano DJ, Zimmet PZ. The worldwide epidemiology of type 2 diabetes mellitus – present and future perspectives. Nat Rev Endocrinol 2012; 8: 228-36.
[22]
UK Prospective Diabetes Study (UKPDS) Group. Intensive blood glucose control with sulfonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998; 352: 837-53.
[23]
UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998; 352: 854-65.
[24]
Jagnani VK, Bhattacharya NR, Satpathy SC, et al. Effect of hydroxychloroquine on type 2 diabetes mellitus unresponsive to more than two oral antidiabetic agents. J Diabetes Metab 2017; 8(10): 771.
[http://dx.doi.org/10.4172/2155-6156.1000771]
[25]
Surendra PS. Comparative study to evaluate effect of hydroxychloroquine versus sitagliptin as add on therapy in patients with type 2 diabetes inadequately controlled on combination with metformin and gliclazide: a multicentre, observational trial. Sch J App Med Sci 2018; 6(5): 2150-6.
[26]
Baidya A, Kumar M, Pathak SK, et al. Study of comparative effect of hydroxychloroquine and vildagliptin on glycaemic efficacy and HbA1c in type 2 diabetes patients who were inadequately controlled with metformin and glimepiride dual therapy. JMSCR 2018; 6(4): 409-15.
[http://dx.doi.org/10.18535/jmscr/v6i4.6 8]
[27]
Baidya A, Chakravarti HN, Saraogi RK, et al. Efficacy of maximum and optimum doses of hydroxychloroquine added to patients with poorly controlled type 2 diabetes on stable insulin therapy along with glimepiride and metformin: association of high sensitive c-reactive protein (Hs-CRP) and glycosylated haemoglobin (HbA1c). Endocrinol Metab Syndr 20118; 7: 283.
[28]
Ranjan P, Ahsan S, Bhushan R, et al. Comparison of effi cacy and safety of hydroxychloroquine and teneligliptin in type 2 diabetes patients who are inadequately controlled with glimepiride, metformin and insulin therapy: A randomized controlled trial with parallel group design. Ann Clin Endocrinol Metabol 2018; 2: 30-40.
[http://dx.doi.org/10.29328/journal.acem.1001009]
[29]
Kumar V, Singh MP, Singh AP, Pandey MS, Kumar S, Kumar S. Efficacy and safety of hydroxychloroquine when added to stable insulin therapy in combination with metformin and glimepiride in patients with type 2 diabetes compare to sitagliptin. Int J Basic Clin Pharmacol 2018; 7: 1959-64.
[30]
Singh UP, Baidya A, Singla M, et al. Efficacy and safety of substituting teneligliptin with hydroxychloroquine in inadequately controlled type 2 diabetes subjects with combination therapy of teneligliptin, metformin and glimepiride with or without other antidiabetic therapy: The TENE-HYQ SHIFT Study. Clinical Diabetology 2018; 7(5): 209-14.
[http://dx.doi.org/10.5603/DK.2018.0025]
[31]
Larkin ME, Capasso VA, Chen CL, et al. Measuring psychological insulin resistance: Barriers to insulin use. Diabetes Educ 2008; 34(3): 511-7.
[32]
Peyrot M, Rubin RR, Lauritzen T, et al. Resis tance to insulin therapy among patients and providers results of the cross-national diabetes attitudes, wishes, and needs (DAWN) study. Diabetes Care 2005; 28(11): 2673-9.
[33]
Finelli C, Sommella L, Gioia S, La Sala N, Tarantino G. Should visceral fat be reduced to increase longevity? Ageing Res Rev 2013; 12(4): 996-1004.
[http://dx.doi.org/10.1016/j.arr.2013.05.007]
[34]
Katherine C. 1 Anni W, David RS, Pamela AGC, Cruz MI, Alan Z, Robert C. Hydroxychloroquine inhibits autophagy to potentiate antiestrogen responsiveness in ER+ breast cancer. Clin Cancer Res 2014; 20(12): 3222-32. Erratum in: Clin Cancer Res. 2016 Jun 1; 22 (11): 2825.
[http://dx.doi.org/10.1158/1078-0432.CCR-13-3227]
[35]
Abdel-Hamid AAM, Firgany AEL. Favorable outcomes of hydroxychloroquine in insulin resistance may be accomplished by adjustment of the endothelial dysfunction as well as the skewed balance of adipokines. Acta Histochem 2016; 118(6): 560-73.
[http://dx.doi.org/10.1016/j.acthis.2016.06.002]
[36]
Rezabakhsh A, Montazersaheb S, Nabat E, et al. Effect of hydroxychloroquine on oxidative/nitrosative status and angiogenesis in endothelial cells under high glucose condition. Bioimpacts 2017; 7(4): 219-26.
[http://dx.doi.org/10.15171/bi.2017.26]
[37]
Lillegraven S, Greenberg JD, Reed GW, et al. Immunosuppressive treatment and the risk of diabetes in rheumatoid arthritis. PLoS One 2019; 14(1)e0210459
[http://dx.doi.org/10.1371/journal.pone.0210459]

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