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
Keywords:Hydroxychloroquine, HbA1c, Glimepiride, Insulin, Metformin, T2DM, Sitagliptin
Background: The trial was done to evaluate the efficacy and tolerability of hydroxychloroquine when added to stable insulin therapy in combination with metformin and glimepiride in patients with type 2 diabetes (T2DM) compare to sitagliptin.
Methods: After two weeks run in period, eligible patients inadequately controlled on long acting, intermediate acting or premixed insulin (HbA1c ≥7.5% and ≤10%), in combination with metformin and glimepiride were randomised 1:1 to the addition of once daily hydroxychloroquine 400mg or sitagliptin 100mg over 24weeks study period. The primary endpoint was HbA1c change from baseline at week 24. Home based glucometer was used to determine finger stick glucose value to detect hypo or hyperglycemia periodically.
Results: At 24 weeks, the addition of hydroxychloroquine significantly (p <0.001) reduced HbA1c by 1.3% compared with Sitagliptin which was 0.9%. A greater proportion of patients achieved an HbA1c level <7% while randomised to Hydroxychloroquine as compared with sitagliptin (31 vs. 18% respectively; p <0.001). The addition of hydroxychloroquine significantly (p<0.001) reduced fasting plasma glucose by 31.0mg/dl (vs 23.2mg/dl with sitagliptin) and post prandial plasma glucose by 52.1mg/dl (vs 41mg/dl with sitagliptin) relative to sitagliptin. The difference in mean value of total daily insulin dose showed a highly significant decrease (P <0.0001) from baseline to end of the treatment with hydroxychloroquine i.e. from 41±10.2 to 31.87±16.49 IU as compare to sitagliptin i.e. from 41±10.6 to 37.91±11.71 IU. And also highly significant (P <0.0001) decrease in mean weight was observed at the end of trial with hydroxychloroquine.
Conclusions: Hydroxychloroquine decreases HbA1c in patients whose type 2 diabetes is poorly controlled with stable-dose insulin therapy with metformin and glimepiride.
Gerstein HC, Pais P, Pogue J, Yusuf S: Relationship of glucose and insulin levels to the risk of myocardial infarction: a case controlled study. J Am Coll Cardiol. 199; 3:612-9.
Reaven GM: Pathophysiology of insulin resistance in human disease. Phys Rev. 1997;75:473-86.
Matthews DR, Cull CA, Stratton IM, Holman RR, Turner RC: UKPDS 26: Sulphonylurea failure in non-insulin-dependent diabetic patients over six years: UK Prospective Diabetes Study (UKPDS) Group. Diabet Med. 1998;15:297-303.
Turner RC, Cull CA, Frighi V, Holman RR. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group. JAMA 1999;281:2005-12.
Hermansen K, Davies M, Derezinski T, Martinez RG, Clauson P, Home P. A 26-week, randomized, parallel, treat-to-target trial comparing insulin detemir with NPH insulin as add-on therapy to oral glucose-lowering drugs in insulin-naive people with type 2 diabetes. Diabetes Care. 2006;29:1269-74.
Riddle MC, Rosenstock J, Gerich J. The treat-to-target trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients. Diab Care. 2003;26:3080-6.
Karasik A, Aschner P, Katzeff H, Davies MJ, Stein PP. Sitagliptin, a DPP-4 inhibitor for the treatment of patients with type 2 diabetes: a review of recent clinical trials. Curr Med Res Opin. 2008;24:489-96.
Pareek A, Chandurkar N, Thomas N. 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;30:1257-66.
Jagnani VK, Bhattacharya NR, Satpathy SC, Hasda GC, Chakraborty S. Effect of hydroxychloroquine on type 2 diabetes mellitus unresponsive to more than two oral antidiabetic agents. J Diabetes Metab. 2017;8:771.
Baidya A, Kumar Manish, Sailesh KP, Ahamed R. Study of comparative effect of hydroxychloroquine and vildagliptin on glycaemic efficacy and HbA1cin type 2 diabetes patients who were inadequately controlled with metformin and glimepiride dual therapy. JMSCR. 2018;6(4).
Prasad SS, Kumar SM, Kumar A, Alok, Ranjan R. 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. Scholars Journal of Applied Medical Sciences. 2018;6(5).
Baidya A, Chakravarti HN, Saraogi RK, Gupta A, Ahmed R, 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. 2018;7:283-7.
Vilsbøll T, Rosenstock J, Yki‐Järvinen H, Cefalu WT, Chen Y, Luo E, et al. Efficacy and safety of sitagliptin when added to insulin therapy in patients with type 2 diabetes. Diab Obes Metabol 2010 Feb;12(2):167-77.
Haupt E, Laube F, Loy H, Schöffling K. Secondary failures in modern therapy of diabetes mellitus with blood glucose lowering sulfonamides. Medical Clinic.1977; Sep;72(38):1529-36.
Groop L, Schalin C, Franssila-Kallunki A, Widén E, Ekstrand A, Eriksson J. Characteristics of non-insulin-dependent diabetic patients with secondary failure to oral antidiabetic therapy. Am J Med. 1989 Aug 1;87(2):183-90.
Harris MI, Klein R, Welborn TA, Knuiman MW. Onset of NIDDM occurs at least 4-7 yr before clinical diagnosis. Diabetes care. 1992 Jul 1;15(7):815-9.
Pi-Sunyer FX. The effects of pharmacologic agents for type 2 diabetes mellitus on body weight. Postgrad Med. 2008 Jan 1;120(2):5-17.
Inzucchi SE. Oral antihyperglycemic therapy for type 2 diabetes: scientific review. JAMA. 2002 Jan 16;287(3):360-72.
Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Eng J Med. 2008 Oct 9;359(15):1577-89.