Effectiveness and Safety of Hydroxychloroquine compared to Teneligliptin in uncontrolled T2DM patients as add-on therapy

Amit Kumar, Akhouri Sukrit Prakash

Abstract

Objectives. Hydroxychloroquine (HCQ) 400 mg is approved by the Drug Controller General of India (DCGI) and recommended by the Research Society for the Study of Diabetes in India (RSSDI) clinical practice recommendations 2017 as add-on therapy after metformin and sulfonylurea in Type 2 Diabetes (T2DM) patients. The aim of this observational study is to compare the efficacy and safety of hydroxychloroquine 400 mg and teneligliptin 20 mg when used as add-on therapy in Indian Type 2 DM patients who were inadequately controlled (HbA1c ≥7.5%) with metformin 1000 mg and glimepiride 2 mg combination.

Methodology. This study is a prospective observational study to be conducted in 2 diabetic centres of Patna city between October 2017 and May 2018 involving 180 patients followed up for 6 months. One group (N=90) of patients received hydroxychloroquine 400 mg + metformin 1000 mg + glimepiride 2 mg, the other group (N=90) received teneligliptin 20 mg + metformin 1000 mg + glimepiride 2 mg. Efficacy was assessed by fasting blood glucose (FBG), post prandial blood glucose (PPBG) and glycated haemoglobin (HbA1c) reduction. Safety was evaluated by the number of hypoglycaemic events and changes in serum creatinine levels. Home based glucose monitoring was used to detect the hypoglycaemic events. Patients who had any type of retinopathy/maculopathy were excluded.

Results. Mean age of entire population was 66 ± 8 years with mean 6 ± 2 years of DM with 102 males. Mean body weight was 71 ± 12 kg. Baseline HbA1c was 8.1 ± 0.3 in the hydroxychloroquine group and 8.2 ± 0.2 in the teneligliptin group.

At 24 weeks there were statistically significant reductions in mean HbA1c in the hydroxychloroquine group (1.1 ± 0.3) as compared to the teneligliptin group (0.82 ± 0.3) (P≤0.001). The mean FBG and PPBG was 169 ± 18 mg/dl and 232 ± 18 mg/dl respectively in hydroxychloroquine group which was reduced to 121 ± 15 mg/dl and 161 ± 19 mg/dl at the end of 24 weeks. In the teneligliptin group, FBG and PPBG was 171 ± 16 mg/dl and 239 ± 21 mg/dl at baseline, which was reduced to 121 ± 15 mg/dl and 161 ± 19 mg/dl respectively in same period of time (P≤ 0.005). There were 4 incidences of hypoglycaemic events in the hydroxychloroquine group (4.4%) and 6 in the teneligliptin group (6.67%). No patients required medical assistance for hypoglycaemic events. There was no statistically significant change in body weight in both the groups. No marked changes in creatinine levels were found in patients in both the groups.

Conclusion. In conclusion, treatment with hydroxychloroquine 400 mg for 24 weeks reduces glycaemic parameters more aggressively than teneligliptin 20 mg in Indian type 2 diabetes patients.

Keywords

hydroxychloroquine, teneligliptin, FBG, PPBG, HbA1c

Full Text:

Abstract HTML PDF

References

Unnikrishnan R, Anjana RM, Mohan V. Diabetes mellitus and its complications in India. Nat Rev Endocrinol. 2016;12(6):357–70. PMID: 27080137. https://doi.org/10.1038/nrendo.2016.53.

Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352(9131):837-53. PMID: 9742976.

Kahn SE. The relative contributions of insulin resistance and β-cell dysfunction to the pathophysiology of type 2 diabetes. Diabetologia. 2003;46(1):3-19. PMID: 12637977. https://doi.org/10.1007/s00125-002-1009-0.

UK prospective diabetes study 16. Overview of 6 years’ therapy of type II diabetes: A progressive disease. UK Prospective Diabetes Study Group. Diabetes. 1995;44(11):1249-58. PMID: 7589820.

Charbonnel B, Schernthaner G, Brunetti P, et al. Long-term efficacy and tolerability of add-on pioglitazone therapy to failing monotherapy compared with addition of gliclazide or metformin in patients with type 2 diabetes. Diabetología. 2005;48(6):1093–104. PMID: 15889234. https://doi.org/10.1007/s00125-005-1751-1.

Hanefeld M, Brunetti P, Schernthaner GH, Matthews DR, Charbonnel BH; QUARTET Study Group. One-year glycemic control with a sulfonylurea plus pioglitazone versus a sulfonylurea plus metformin in patients with type 2 diabetes. Diabetes Care. 2004;27(1):141-7. PMID: 14693980.

Kahn SE, Haffner SM, Heise MA, et al. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med. 2006;355(23):2427-43. PMID: 17145742. https://doi.org/10.1056/NEJMoa066224.

Rehman MB, Tudrej BV, Soustre J, et al. Efficacy and safety of DPP-4 inhibitors in patients with type 2 diabetes: Meta-analysis of placebo controlled randomized clinical trials. Diabetes Metab. 2017;43(1):48–58. PMID: 27745828. https://doi.org/10.1016/j.diabet.2016.09.005.

Seino Y, Kuwata H, Yabe D. Incretin-based drugs for type 2 diabetes: Focus on East Asian perspectives. J Diabetes Investig. 2016;7 Suppl 1:102-9. PMID: 27186364. PMCID: PMC4854513. http://doi.org/10.1111/jdi.12490.

Hinnen D. Dipeptidyl peptidase-4 inhibitors in diverse patient populations with type 2 diabetes. Diabetes Educ. 2015;41(1 Suppl):19S–31S. PMID: 26453595. https://doi.org/ 10.1177/0145721715609420.

de Wit HM, Te Groen M, Rovers MM, Tack CJ. The placebo response of injectable GLP-1 receptor agonists vs. oral DPP-4 inhibitors and SGLT-2 inhibitors: A systematic review and meta-analysis. Br J Clin Pharmacol. 2016;82(1):301-14. PMID: 26935973 PMCID: PMC4917794. https://doi.org/10.1111/bcp.12925.

Karagiannis T, Paschos P, Paletas K, Matthews DR, Tsapas A. Dipeptidyl peptidase-4 inhibitors for treatment of type 2 diabetes mellitus in the clinical setting: Systematic review and meta-analysis. BMJ. 2012;344:e1369. PMID: 22411919. https://doi.org/10.1136/bmj.e1369.

Aroda VR, Henry RR, Han J, et al. Efficacy of GLP-1 receptor agonists and DPP-4 inhibitors: Meta-analysis and systematic review. Clin Ther. 2012;34(6):1247–58.e22. PMID: 22608780. https://doi.org/10.1016/j.clinthera.2012.04.013.

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. PMID: 24669876. https://doi.org/10.1185/03007995.2014.909393.

Gerstein HC, Thorpe KE, Taylor DW, Haynes RB. 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(3):209-19. PMID: 11850097.

Singh UP, Baidya B, 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. https://doi.org/10.5603/DK.2018.0025.

Rekedal LR, Massarotti E, Garg R, et al. Changes in glycated hemoglobin after initiation of hydroxychloroquine or methotrexate in diabetic patients with rheumatic diseases. Arthritis Rheum 2010;62(12):3569-73. PMID: 20722019. PMCID: PMC2992611. https://doi.org/10.1002/art.27703.

Quatraro A, Consoli G, Magno M, et al. Hydroxychloroquine in decompensated, treatment-refractory noninsulin-dependent diabetes mellitus. A new job for an old drug? Ann Intern Med. 1990;112(9):678-81. PMID: 2110430.

Ranjan P, Ahsan S, Bhushan R, et al. Comparison of efficacy 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;2:030-040. https://doi.org/10.29328/journal.acem.1001009.

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(10):1959-64. http://dx.doi.org/10.18203/2319-2003.ijbcp20183930.

Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352(9131):854-65. PMID: 9742977.

Ross R. Atherosclerosis: An inflammatory disease. N Engl J Med. 1999;340(2):115–26. PMID: 9887164. https://doi.org/10.1056/NEJM199901143400207.

Choy M, Lam S. Sitagliptin: a novel drug for the treatment of type 2 diabetes. Cardiol Rev. 2007;15(5):264-71. PMID: 17700385. https://doi.org/10.1097/CRD.0b013e318123f771.

Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes, 2015: A patient-centered approach: Update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2015;38(1):140-9. PMID: 25538310. https://doi.org/10.2337/dc14-2441.

Detert J, Klaus P, Listing J, et al. Hydroxychloroquine in patients with inflammatory and erosive osteoarthritis of the hands (OA TREAT): Study protocol for a randomized controlled trial. Trials. 2014;15:412. PMID: 25348033. PMCID: PMC4219005. https://doi.org/10.1186/1745-6215-15-412.

Hage MP, Al-Badri MR, Azar ST. A favorable effect of hydroxychloroquine on glucose and lipid metabolism beyond its anti-inflammatory role. Ther Adv Endocrinol Metab. 2014;5(4):77-85. PMID: 25343023. PMCID: PMC4206615. https://doi.org/10.1177/2042018814547204.

Durbin RJ. Thiazolidinedione therapy in the prevention/delay of type 2 diabetes in patients with impaired glucose tolerance and insulin resistance. Diabetes Obes Metab. 2004;6(4):280-5. PMID: 15171752. https://doi.org/10.1111/j.1462-8902.2004.0348.x.

Fujiwara T, Saitoh S, Takagi S, et al. Development and progression of atherosclerotic disease in relation to insulin resistance and hyperinsulinemia. Hypertens Res. 2005;28(8):665-70. PMID: 16392771. https://doi.org/10.1291/hypres.28.665.

Satoh N, Ogawa Y, Usui T, et al. Antiatherogenic effect of pioglitazone in type 2 diabetic patients irrespective of the responsiveness to its antidiabetic effect. Diabetes Care. 2003;26(9):2493-9. PMID: 12941708.

Matsuzawa Y, Funahashi T, Kihara S, Shimomura I. Adiponectin and metabolic syndrome. Arterioscler Thromb Vasc Biol. 2004;24(1):29-33. PMID: 14551151.https://doi.org/ 10.1161/01.ATV.0000099786.99623.EF.

Wasko MC, McClure CK, Kelsey SF, Huber K, Orchard T, Toledo FG. Antidiabetogenic effects of hydroxychloroquine on insulin sensitivity and beta cell function: A randomised trial. Diabetologia. 2015;58(10):2336-43. PMID: 26197707. PMCID: PMC4575248. https://doi.org/10.1007/s00125-015-3689-2.

Belalcazar LM, Reboussin DM, Haffner SM, et al. A 1-year lifestyle intervention for weight loss in individuals with type 2 diabetes reduces high creactive protein levels and identifies metabolic predictors of change. Diabetes Care. 2010;33(11):2297-303. PMID: 20682679. PMCID: PMC2963483. https://doi.org/10.2337/dc10-0728.