Triple Combination Therapy Using Metformin, Thiazolidinedione, and a GLP-1 Analog or DPP-IV Inhibitor in Patients with Type 2 Diabetes Mellitus.
Although there is no HbA1c threshold for cardiovascular risk, the American Diabetic Association-recommended goal of HbA1c < 7.0% appears to be unacceptably high. To achieve an optimal HbA1c level goal of 6.0% or less, a high dosage of sulfonylureas and insulin would be required; the trade-off would be the common adverse effects of hypoglycemia and weight gain. In contrast, hypoglycemia is uncommon with insulin sensitizers and GLP-1 analogs, allowing the physician to titrate these drugs to maximum dosage to reduce HbA1c levels below 6.0% and they have been shown to preserve β-cell function. Lastly, weight gain is common with sulfonylurea and insulin therapy, whereas GLP-1 analogs induce weight loss and offset the weight gain associated with TZDs. A treatment paradigm shift is recommended in which combination therapy is initiated with diet/exercise, metformin (which has antiatherogenic effects and improves hepatic insulin sensitivity), a TZD (which improves insulin sensitivity and preserves β-cell function with proven durability), and a GLP-1 analog (which improves β, α-cell function and promotes weight loss) or a dipeptidyl peptidase IV inhibitor in patients with type 2 diabetes mellitus.
Diabetes Center, Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
Sun Woo
SW
Kim
Diabetes Care. 2010 Jul;33(7):1561-6
20200305
Diabetes Obes Metab. 2007 Mar;9(2):175-85
17300593
N Engl J Med. 2006 Dec 7;355(23):2427-43
17145742
Lancet. 1998 Sep 12;352(9131):837-53
9742976
Cell Metab. 2006 Mar;3(3):153-65
16517403
Trends Endocrinol Metab. 2010 Feb;21(2):59-67
20018525
Clin Ther. 2006 Oct;28(10):1556-68
17157112
Curr Med Res Opin. 2008 Jan;24(1):275-86
18053320
Nat Rev Endocrinol. 2010 May;6(5):253-4
20414319
Am J Med. 2010 Mar;123(3 Suppl):S19-27
20206728
Diabetes Care. 2009 Jul;32(7):1224-30
19289857
J Clin Endocrinol Metab. 2007 Apr;92(4):1249-55
17244786
Diabetes Care. 2010 May;33(5):951-7
20107105
Diabet Med. 2007 Jun;24(6):626-34
17517066
Ann Intern Med. 2007 Apr 3;146(7):477-85
17404349
Diabetes Care. 2005 Aug;28(8):1936-40
16043735
Expert Opin Investig Drugs. 2007 Apr;16(4):533-45
17371200
Diabetes Obes Metab. 2007 Mar;9(2):166-74
17300592
Diabetes Care. 2009 May;32(5):762-8
19196887
Lancet. 1998 Sep 12;352(9131):854-65
9742977
Diabetes Care. 2010 Jun;33(6):1300-3
20332351
Diabetes. 2010 Jun;59(6):1445-50
20332343
Diabetologia. 2006 May;49(5):930-6
16525843
Diabetes. 2009 Apr;58(4):773-95
19336687
Diabetes Care. 2010 Jul;33(7):1691-2
20587731
Diabetes. 2008 Jan;57(1):142-9
17959931
Curr Med Res Opin. 2009 Oct;25(10):2361-71
19650752
Eur J Endocrinol. 2010 Feb;162(2):193-212
19841045
J Clin Endocrinol Metab. 2008 Oct;93(10):3703-16
18628530
Curr Med Res Opin. 2006 Jun;22(6):1211-5
16846554