The review by Mooradian and colleagues concluded that adding a second agent to initial antihyperglycemic monotherapy reduces HbA1c by an additional percentage point. Combination first-line therapy also has the potential to minimize side effects and, when a combination pill is use, enhance adherence. Possible drawbacks include difficulty determining the source of side effects when two agents are initiated simultaneously, the inability to determine whether similar efficacy could have been achieved with a single agent, cost, and the risk of hypoglycemia.3 (Combination oral antihyperglycemic therapy that includes an insulin secretagogue, such as a sulfonylurea, carries a significant risk of hypoglycemia.1)

Current consensus and position statements recommend that the management of type 2 diabetes, including targeted goals, be individualized to take into account factors such as the patient’s age, presence of comorbidities, and risk of hypoglycemia.1,2 The array of drugs currently available for antihyperglycemic therapy makes such individualization possible. 


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1. Garber AJ, Abrahamson MJ, Barzilay JI, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm – 2016 executive summary. Endocr Pract. 2016 Jan;22(1):84-113.

2. Inzucchi SE, Bergenstal RM, Buse JB, t 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 Jan;38(1):140-9. doi:10.2337/dc14-2441.

3. Mooradian AChehade JMMooradian AD. Advantages and pitfalls of antihyperglycemic combination pills as first-line therapy in the management of type 2 diabetes. Am J Ther. 2015 Dec 29; [Epub ahead of print].

4. Chiasson JLNaditch LMiglitol Canadian University Investigator Group. The synergistic effect of miglitol plus metformin combination therapy in the treatment of type 2 diabetes. Diabetes Care. 2001 Jun;24(6):989-94.

5. Henry RR, Murray AV, Marmolego MH, et al. Dapagliflozin, metformin XR, or both: initial pharmacotherapy for type 2 diabetes, a randomized controlled trial. Int J Clin Pract. 2012;66:446-456.

6. Merovci ASolis-Herrera CDaniele G, et al. Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production. J Clin Invest. 2014 Feb;124(2):509-14. doi: 10.1172/JCI70704. Epub 2014 Jan 27.