Abstract
The glycosylated hemoglobin (HbA1c) goal in patients with type 2 diabetes mellitus should be to achieve as low a value as can be obtained without causing significant or frequent hypoglycemia. This is best achieved by utilizing agents that lower glucose levels without causing hypoglycemia (thiazolidinediones and metformin). To maintain these low HbA1c values and avoid the utilization of insulin secretagogues or insulin, which are associated with hypoglycemia and suboptimal dosing leading to higher HbA1c values, drugs that maintain or improve pancreatic β-cell function (thiazolidinediones and possibly incretin-based therapies) should be utilized. Restoration of first-phase insulin release, as has been shown with thiazolidinediones, will not only improve postprandial hyperglycemia but will also improve postprandial hyperlipidemia, both of which will decrease cardiac risk. Utilizing small doses of two drugs will also result in a decreased incidence of adverse effects compared with a large dose of a single drug. The use of fixed-dose combination oral antihyperglycemics will not only improve compliance but will often decrease costs compared with individual component dual therapy.
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References
Bell DSH. Why I initiate therapy with two insulin sensitizers in patients with type 2 diabetes. Endocr Pract 2003; 9: 98–100
Stratton IM, Adler AI, Neil HA, et al. Association of glycemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS): prospective observational study. BMJ 2000; 321: 405–12
Khaw KT, Wareham N, Bingham S, et al. Association of hemoglobin A1c with cardiovascular disease and mortality in adults: the European prospective investigation into cancer in Norfolk. Ann Intern Med 2004; 141(6): 413–20
Garber A, Sankoh S, Mohideen P, et al. Glyburide/metformin tablets versus metformin plus rosiglitazone in type 2 diabetes patients uncontrolled on metformin: attaining glycemic goals. Diabetes 2003; 52Suppl. 1: A119–20
Bell DSH, Ovalle F. Outcomes of initiation of therapy with once daily combination of a thiazolidinedione and a biguanide at an early stage of type 2 diabetes. Diabetes Obes Metab 2004; 6(5): 363–6
Bell DSH, Yumuk V. Frequency of severe hypoglycemia in patients with non-insulin-dependent diabetes mellitus treated with sulfonylureas or insulin. Endocr Pract 1997; 3: 281–3
Raskin P, Bode BW, Marks JB, et al. Continuous subcutaneous insulin infusion and multiple daily injection therapy are equally effective in type 2 diabetes: a randomized, parallel-group, 24-week study. Diabetes Care 2003; 26(9): 2598–603
Unger RH. Lipotoxicity in the pathogenesis of obesity-dependent NIDDM: genetic and clinical implications. Diabetes 1995; 44: 863–70
Petersen KF, Dufour S, Befroy D, et al. Impaired mitochondrial activity in insulin-resistant offspring of patients with type 2 diabetes. N Engl J Med 2004; 350(7): 664–71
Bell DSH. β-Cell rejuvenation with thiazolidinediones. Am J Med 2003; 115(8A): 20S–3S
Cnop M, Grupping A, Hoorens A, et al. Endocytosis of low-density lipoprotein by human pancreatic β cells and uptake in lipid-storing vesicles, which increases with age. Am J Pathol 2000; 156: 237–44
Butler AE, Janson J, Bonner-Weir S, et al. β-cell deficit and increased β-cell apoptosis in humans with type 2 diabetes. Diabetes 2003; 52: 102–10
Wallace TM, Matthews DR. Poor glycemic control in type 2 diabetes: a conspiracy of disease, suboptimal therapy and attitude. QJM 2000; 93: 369–74
Finegood DT, McArthur MD, Kojwang D, et al. β-cell mass dynamics in Zucker diabetic fatty rats: rosiglitazone prevents the rise in net cell death. Diabetes 2001; 50: 1021–9
Fonseca V, Rosenstock J, Patwardhan R, et al. Effect of metformin and rosiglitazone combination therapy in patients with type 2 diabetes mellitus: a randomized controlled trial. JAMA 2000; 283: 1695–702
Smith SA, Porter LE, Biswas N, et al. Rosiglitazone, but not glyburide, reduces circulating proinsulin and the proinsulin: insulin ratio in type 2 diabetes. J Clin Endocrinol Metab 2004; 89(12): 6048–53
Kahn SE. The importance of the beta-cell in the pathogenesis of type 2 diabetes mellitus. Am J Med 2000; 108Suppl. 6a: 2S–8S
Bell DSH. Management of type 2 diabetes with thiazolidinedione: link between β-cell preservation and durability of response. Endocrinologist 2004; 14(5): 293–9
Bell DSH, Mayo MS. Outcome of metformin-facilitated reinitiation of oral diabetic therapy in insulin-treated patients with non-insulin-dependent diabetes mellitus. Endocr Pract 1997; 3: 73–6
Ovalle F, Bell DSH. Clinical evidence of thiazolidinedione-induced improvement of pancreatic beta cell function in patients with type 2 diabetes mellitus. Diabetes Obes Metab 2002; 4: 56–9
Bell DSH, Ovalle F, Shadmany S. Conversion from troglitazone to rosiglitazone [letter]. Endocr Pract 2001; 7: 326
Ovalle F, Bell DSH. Effect of rosiglitazone versus insulin on the pancreatic β-cell function of subjects with type 2 diabetes. Diabetes Care 2004; 27(11): 2585–9
Rosenstock J, Goldstein BJ, Wooddell MJ, et al. Greater benefits of rosiglitazone added to submaximal dose of metformin compared to maximizing metformin dose in type 2 diabetes mellitus patients. Diabetes 2004; 52Suppl. 2: A144–5
DeMan FH, Castro Cabezus M, van Barlinger HH, et al. Triglyceride-rich lipoproteins in non-insulin-dependent diabetes mellitus: postprandial metabolism and relation to premature atherosclerosis. Eur J Clin Invest 1996; 26: 89–108
Ceriello A, Hanefeld M, Leiter L, et al. Postprandial glucose regulation and diabetic complications. Arch Intern Med 2004; 164: 2090–5
Tan GD, Fielding BA, Currie JM, et al. The effects of rosiglitazone on fatty acid and triglyceride metabolism in type 2 diabetes. Diabetologia 2005; 48(1): 83–95
Van Wijk JPH, deKoning EJP, Castro Cabezas M, et al. Rosiglitazone improves postprandial triglyceride and free fatty acid metabolism in type 2 diabetes. Diabetes Care 2005; 28: 844–9
Chiasson JL, Josse RG, Gomis R, et al. Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: the STOP-NIDDM trial. JAMA 2003; 290(4): 486–94
Delorme S, Chiasson JL. Acarbose in the prevention of cardiovascular disease in subjects with impaired glucose tolerance and type 2 diabetes mellitus. Curr Opin Pharmacol 2005; 5(2): 184–9
Buchwald H, Avidor Y, Braunwald E, et al. Bariatric surgery: a systematic review and meta-analysis. JAMA 2004; 292(14): 1724–37
Guldstrand M, Ahren B, Wredling R, et al. Improved β-cell function after standardized weight reduction in severely obese subjects. Am J Physiol Endocrinol Metab 2003; 284(3):E557–65
Brubaker PL, Drucker DJ. Glucagon-like polypeptides regulate cell proliferation and apoptosis in the pancreas, gut, and central nervous system. Endocrinology 2004; 145: 2653–9
Zander M, Madsbad S, Madsen JL, et al. Effect of 6-week course of glucagon-like peptide-1 on glycemic control, insulin sensitivity and β-cell function in type 2 diabetes: a parallel-group study. Lancet 2002; 359: 824–30
Bell DSH, Ovalle F. Long-term glycemic efficacy and weight changes associated with thiazolidinediones when added at an advanced stage of type 2 diabetes. Diabetes Obes Metab 2006 Jan; 8(1): 110–5
Gomez-Perez FJ, Fanghanel-Salmon G, Antonio-Barbosa J, et al. Efficacy and safety of rosiglitazone plus metformin in Mexicans with type 2 diabetes. Diabetes Metab Res Rev 2002; 18: 127–34
Strowig SM, Aviles-Santa ML, Raskin P. Improved glycemic control without weight gain using triple therapy in type 2 diabetes. Diabetes Care 2004; 27(7): 1577–83
Vanderpoel DR, Hussein MA, Watson-Heidari T, et al. Adherence to a fixed-dose combination of rosiglitazone maleate/metformin hydrochloride in subjects with type 2 diabetes mellitus: a retrospective database analysis. Clin Ther 2004; 26(12): 2066–75
Leichter SB, Thomas S. Combination medications in diabetes care: an opportunity that merits more attention. Clinical Diabetes 2003; 21: 175–8
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Bell, D.S.H. The Case for Combination Therapy as First-Line Treatment for the Type 2 Diabetic Patient. Mol Diag Ther 5, 131–137 (2006). https://doi.org/10.2165/00024677-200605030-00001
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DOI: https://doi.org/10.2165/00024677-200605030-00001