EFFECT OF SITAGLIPTIN ON GLYCEMIC CONTROL, BODY WEIGHT, BLOOD PRESSURE AND SERUM LIPID PROFILE IN TYPE 2 DIABETIC HYPERLIPIDEMIC PATIENTS
AbstractBackground: Dyslipidaemia is a global health issue in developed as well as in developing countries. People with type 2 Diabetes mellitus are more susceptible to develop dyslipidaemia and its related complications. The objective of the study was to assess the effect of sitagliptin a (DPP-4 inhibitor) oral antidiabetic drug on blood sugar, body weight, blood pressure and dyslipidaemia in type 2 diabetic patients. Methods: This 12 weeks open label observational study was conducted at outdoor of diabetic clinic of Sheikh Zayed Medical College/Hospital, Rahim Yar Khan in which newly diagnosed type 2 diabetic patients (n=78) with poor glycaemic control(HbA1c >7.2%) were selected. The patient received sitagliptin 50 mg twice daily for 12 weeks. Results: After 12 weeks treatment with sitagliptin, there was a significant reduction in the value of HbA1c from 8.184%±0.467 at baseline to 7.0200%±0.459 at 12 weeks (p<0.05). Body weight also decreased significantly from 80.21kg±7.156 at baseline to 71.74 kg±6.567 at 12 weeks (p<0.05).Systolic blood pressure decreased (SBP) decreased significantly from 138.17±6.050 mmHg at baseline to 131.22±6.311 mmHg at 12 weeks (p<0.05). Significant changes were also seen in diastolic blood pressure which decreased from 83.14±6.714 mmHg at baseline to 75.28±6.481 mmHg at 12 weeks (p<0.05). Significant reduction in the serum level of total Cholesterol (TC), triglycerides (TG) and Low density lipoprotein cholesterol (LDL-C) were detected (TC: 222.09±13.538 to 209.41±13.475 mg/dl, p<0.05; TG: 170.99±6.940 to 143.45±8.279 mg/dl, p<0.05; LDL-C 120.00±5.804 to 109.06±6.278 mg/dl, p<0.05). High density lipoprotein cholesterol (HDL-C) increased significantly from 42.99±4.836 mg/dl at baseline to 49.97±3.490 mg/dl at 12 weeks. Conclusion: Sitagliptin not only improves blood glucose control but also body weight, blood pressure and lipid profile in type 2 diabetic hyperlipidaemia patientsKeywords: Sitagliptin, Diabetes Mellitus, HbA1c, Blood pressure, Lipid profile, body weight
Libby P. The pathogenesis, prevention and Treatment of Atherosclerosis. In: Fauci AS, editor. Harrison’s principles of internal medicine. 17th ed. New York: McGraw-Hill Medical; 2008. p.1501–9.
Bertolotti M, Maurantonio M, Gabbi C, Anzivino C, Carulli N. Review article Hyperlipidemia and cardiovascular risk. Aliment Pharmacol Ther 2005:22:28–30.
Dunn FL. Management of dyslipidaemia in people with type 2 diabetes mellitus. Rev Endocr Mctab Disord 2010:11(1): 41–51.
Tahrani AA, Bailey CJ, Del Prato S, Barnett AH. Manangement of type 2 diabetes: new and future developments in treatment. Lancet 2011:378(9786):182–97.
Duez H, Cariou B, Staels, B. DPP-4 inhibitors in the treatment of type 2 diabetes. Biochem Pharmacol 2012:83(7):823–32.
Tanaka T, Nangaku M, Nishiyama A. The role if incretin in salt- sensitive hypertension: the potential use of dipeptidyl peptidase -1v inhibitors. Curr Opin Nephrol Hypertens 2011:20(5):476–81.
Brown NJ. Cardiovascular effects of antidiabetic agent: focus on blood pressure effects of incretin based therapies. J Am Soc Hypertens 2012:6(3):163–8.
Farr S, Adeli K. Incretin based therapies for treatment of postprandial dyslipidaemia in insulin resistant states. Curr Opin Lipidol 2012:23(1):56–61.
Makdissi A, Ghanium H, Vora M, Green K, Abuaysheh S, Chaudhuri A, et al. Sitagliptin exerts an antiinflammatory action. J Clin Endocrinol Metab 2012:97(9):3333–41.
Rizzo MR, Barbieri M, Marfella R, Paolisso G. Reduction of oxidative stress and inflammation by blunting daily acute glucose fluctuations in patients with type 2 diabetes: role of dipeptidyl peptidase-IV inhibition. Diabetes Care 2012:35(10):2076–82.
Van PC, Netea MG, Smits P, Tack CJ. Vidagliptin improves endothelium dependent vasodilatation in type 2 diabetes. Diabetes Care 2011:34 (9):2072–7.
Gupta AK, Verma AK, Kailashiya J, Singh SK, Kumar N. Sitagliptin: Anti-platelet effect in diabetes and healthy volunteers. Platelets 2012:23(8):565–70.
Scheen AJ. Cardiovascular effect of gliptins. Nature Rev Cardiol 2013:10(2):73–84.
Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holmann RR, Sherwin R, et al. Medical manangement of hyperglycemia 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(1):193–203.
Hermansen K, Mortensen LS. Body weight changes associated with antihyperglycemic agents in type 2 diabetes mellitus. Drug Saf 2007:30(12):1127–42.
Mitry J, Hamdy O. Diabetes medication and body weight. Expert Opin Drug Saf 2009:8(5):573–84.
Ismail-Beigi F. Clinical practice. Glycemic manangement of type 2 diabetes mellitus. N Engl J Med 2012:366(14):1319–27.
Arechavaleta R, Seck T, Chen Y, Krobot KJ, Duran L, Kaufiman, et al. Efficacy and safety of treatment with sitagliptin or glimepiride in patients with type 2 diabetes inadequately controlled on metformin monotherapy: a randomized , double blind, non inferiority trial. Diabetes Obes Metab 2011:13(2):160–8.
Bunck MC, Diamant M, Corner A, Eliasson B, Malloy JL, Shaginian RM, et al. One year treatment with exenatide improves β- cell function, compared with insulin glargine, in metformin treated type 2 diabetic patients. Diabetes Care 2009:32(5):762–8.
Wing RR, Lang W, Wadden TA, Safford M, Knowler WC, Bertoni AG, et al. Benefits of modest weight loss in improving cardiovascular risk factors in over weight obese individuals with type 2 diabetes. Diabetes Care 2011:34(7):1481–6.
Ban K, Noyan-Ashraf MH, Hoefer J, Bolz SS, Drucker DJ, Husain M. Cardioprotective and vasodilatory action of glucagon like peptide 1 receptor dependent and independent pathways. Circulation 2008:117(18):2340–50.
Gutzwiller JP, Tschopp S, Block A, Zehnder CE, Huber AR, Kreyenbuehl M, et al. Glucagon like peptide 1 induces natriuresis in healthy subjects and in insulin resistant obese men. J Clin Endocrinol Metab 2004:89(6):3055–61.
Mistry GC, Maes AL, Lassester KC, Davies MJ, Gottesdiener KM, Wagner JA, et al. Effect of sitaglipitin, a dipeptidyl peptidase-4 inhibitor, on blood pressure in nondiabetic patient with mild to moderate hypertension. J Clin Pharmacol 2008:48(5):592–8.
Ogawa S, Ishiki M, Nako K, Okamura M, Senda M, Mori T, et al. Sitaglipitin, a dipeptidyl peptidase-4 inhibitor, decreases systolic blood pressure in Japanese hypertensive patients with type 2 diabetes. Tohoku J Exp Med 2012:223(2):133–5.
Qin X, Shen H, Liu M, Yang Q, Zheng S, Sabo M, et al. GLP-1 reduces intestinal lymph flow, triglycerides absorption and apolipoprotein production in rats. Am J Physiol Gastrointest Liver Physiol 2005:288(5):943–9.
Tremblay AJ, Lamarche B, Kelly I, Charest A, Lepine MC, Droit A, et al. Effect of sitagliptin therapy on triglycerides rich lipoprotein kinetics in patient with type 2 diabetes. Diabetes Obes Metab 2014:16(12):1223–9.
Monami M, Vitale V, Ambrosio M, Bartoli N, Toffanello G, Ragghianti B, et al. Effects on lipid profile of dipeptidyl peptidase 4 inhibitors, pioglitazone, acarbose, and sulfonylureas: meta-analysis of placebo-controlled trials. Adv Ther 2012;29(9):736–46.
Kiortsis DN, Filippatos TD, Mikhailidis DP, Elisaf MS, Liberopoulos EN. Statin associated adverse effect beyond muscle and liver toxicity. Atherosclerosis 2007:195(1):7–16.
Para JL, Reddy KR. Hepatotoxicity of hypolipidemic drugs. Clin Liver Dis 2003:7(2):415–33.
Trifiro G. Drug- drug interaction and statin therapy. South Med J 2006:99(12):1325–6.
Cernea S, Raz I. Therapy in the early stage: incretins. Diabetes Care 2011:34(Suppl 2):S264–71.