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Physicians' Prescribing Patterns for Patients with Diabetes Are Changing for the Better

      To the Editor:
      Desai et al
      • Desai N.R.
      • Shrank W.H.
      • Fischer M.A.
      • et al.
      Patterns of medication initiation in newly diagnosed diabetes mellitus: quality and cost implications.
      reported that 35% of patients with type 2 diabetes initiating oral hypoglycemic therapy did not receive the initial therapy with metformin recommended by the 2009 algorithm of the American Diabetes Association (ADA) and European Association for the Study of Diabetes (EASD). The 2009 ADA/EASD Algorithm
      • Nathan D.M.
      • Buse J.B.
      • Davidson M.B.
      • et al.
      American Diabetes Association; European Association for Study of Diabetes
      Medical management 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.
      has recently been superseded by a new Position Statement from those 2 organizations.
      • Inzucchi S.E.
      • Bergenstal R.M.
      • Buse J.B.
      • et al.
      American Diabetes Association (ADA); European Association for the Study of Diabetes (EASD)
      Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).
      The 2012 statement also recommends metformin as the drug of first choice when initiating monotherapy and as part of dual or triple therapy. The American Association of Clinical Endocrinologists (AACE)/American College of Endocrinology (ACE) algorithm of 2009,
      • Rodbard H.W.
      • Jellinger P.S.
      • Davidson J.A.
      • et al.
      Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control.
      not discussed by Desai et al,
      • Desai N.R.
      • Shrank W.H.
      • Fischer M.A.
      • et al.
      Patterns of medication initiation in newly diagnosed diabetes mellitus: quality and cost implications.
      also recommended metformin as the preferred modality of therapy both for monotherapy and combination therapy. However, metformin is contraindicated in a variety of situations, and it is not well tolerated by many patients, so multiple options are needed. The AACE/ACE Algorithm considered 4 alternative forms of initial monotherapy (DPP-4 inhibitors, GLP-1 analogs, thiazolidinediones, and alpha-1-glucosidase inhibitors), and also noted that it may be necessary to use insulin as the initial form of therapy (Figure) . In contrast to the ADA/EASD algorithm
      • Nathan D.M.
      • Buse J.B.
      • Davidson M.B.
      • et al.
      American Diabetes Association; European Association for Study of Diabetes
      Medical management 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.
      and position statement,
      • Inzucchi S.E.
      • Bergenstal R.M.
      • Buse J.B.
      • et al.
      American Diabetes Association (ADA); European Association for the Study of Diabetes (EASD)
      Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).
      the AACE/ACE algorithm
      • Rodbard H.W.
      • Jellinger P.S.
      • Davidson J.A.
      • et al.
      Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control.
      recommended avoiding the use of sulfonylureas (SUs) or glinides for monotherapy. AACE/ACE
      • Rodbard H.W.
      • Jellinger P.S.
      • Davidson J.A.
      • et al.
      Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control.
      recommended initiating therapy with dual therapy if the presenting A1C is above 7.5%, and dual or triple therapy or insulin therapy if the A1C is above 9.0%. Thus, it is not surprising that Desai et al
      • Desai N.R.
      • Shrank W.H.
      • Fischer M.A.
      • et al.
      Patterns of medication initiation in newly diagnosed diabetes mellitus: quality and cost implications.
      reports that 35% of patients do not receive metformin monotherapy as their initial therapy in view of the multiple treatment options available, the fact that the 2009 ADA/EASD algorithm is only 1 of many available algorithms and guidelines, and because metformin often is not appropriate due to patient age (> 80 y), impaired renal function, other risk factors for lactic acidosis, and other situations.
      Figure thumbnail gr1
      FigureChanges in patterns of medication use, 1997-2000
      • Inzucchi S.E.
      • Bergenstal R.M.
      • Buse J.B.
      • et al.
      American Diabetes Association (ADA); European Association for the Study of Diabetes (EASD)
      Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).
      and 2006-2008.
      • Desai N.R.
      • Shrank W.H.
      • Fischer M.A.
      • et al.
      Patterns of medication initiation in newly diagnosed diabetes mellitus: quality and cost implications.
      Closed circles=sulfonylureas (SUs); open squares=metformin; closed triangles=thiazolidinediones (TZDs); open diamonds=dipeptidyl-peptidase-4 (DPP-4) inhibitors.
      Combining the data of Desai et al
      • Desai N.R.
      • Shrank W.H.
      • Fischer M.A.
      • et al.
      Patterns of medication initiation in newly diagnosed diabetes mellitus: quality and cost implications.
      with those of a previous study,
      • Rodbard H.W.
      • Jellinger P.S.
      A critique of the 2012 ADA/EASD position statement (Letter to the Editor).
      one can identify systematic changes in patterns of medication use from 1996 to 2008 (Figure). Metformin use has increased from 21% to 65%. Sulfonylurea (SU) use decreased from 50% to 20%. Thiazolidinediones (TZDs) reached a peak and then declined. Dipeptidyl-peptidase-4 (DPP-4) inhibitors began with the introduction of sitagliptin in 2006 and continue to grow. AACE/ACE recommends that SUs be avoided due to their high risk of hypoglycemia, weight gain, limited duration of effectiveness,
      • Rodbard H.W.
      • Jellinger P.S.
      • Davidson J.A.
      • et al.
      Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control.
      and possible accelerated loss of beta cell function. AACE/ACE recommended minimizing the use of TZDs in view of weight gain, fluid retention, risk of fractures,
      • Rodbard H.W.
      • Jellinger P.S.
      • Davidson J.A.
      • et al.
      Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control.
      and reported association with bladder cancer. AACE/ACE recommends DPP-4 inhibitors and glucagon-like-peptide-1 (GLP-1) receptor agonists because of their low risk of hypoglycemia, weight neutrality and weight loss (respectively), and potential improvement of beta cell function.
      • Rodbard H.W.
      • Jellinger P.S.
      • Davidson J.A.
      • et al.
      Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control.
      We have recently compared more than 25 aspects of the 2009 ADA/EASD algorithm, the 2009 AACE/ACE algorithm, and the 2012 ADA/EASD Position Statement in detail.
      • Rodbard H.W.
      • Jellinger P.S.
      A critique of the 2012 ADA/EASD position statement (Letter to the Editor).
      Medication cost represents only 10% of the total cost of management of patients with diabetes. Eighty percent of the cost of diabetes is related to hospitalizations and complications. Use of more expensive but safer incretin-based medications such as DPP-4 inhibitors and GLP-1 analogs can reduce the total cost of management. One emergency department visit for a hypoglycemic episode can eradicate the cost savings of “inexpensive” medications such as sulfonylureas. Physicians’ prescribing patterns are changing (Figure).
      • Desai N.R.
      • Shrank W.H.
      • Fischer M.A.
      • et al.
      Patterns of medication initiation in newly diagnosed diabetes mellitus: quality and cost implications.
      • Cohen F.J.
      • Neslusan C.A.
      • Conklin J.E.
      • Song X.
      Recent antihyperglycemic prescribing trends for US privately insured patients with type 2 diabetes.
      The reduced usage of SUs and TZDs and increasing use of metformin, DPP-4 inhibitors, and GLP-1 agonists are highly desirable and consistent with the AACE algorithm.
      • Rodbard H.W.
      • Jellinger P.S.
      • Davidson J.A.
      • et al.
      Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control.
      • Rodbard H.W.
      • Jellinger P.S.
      A critique of the 2012 ADA/EASD position statement (Letter to the Editor).
      Physicians should minimize the overall cost of care by selecting medications that are both efficacious and safe. Physicians must avoid clinical inertia and adjust therapy as frequently as needed to achieve appropriate goals—carefully customized for each individual.
      • Inzucchi S.E.
      • Bergenstal R.M.
      • Buse J.B.
      • et al.
      American Diabetes Association (ADA); European Association for the Study of Diabetes (EASD)
      Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).
      • Rodbard H.W.
      • Jellinger P.S.
      • Davidson J.A.
      • et al.
      Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control.
      • Rodbard H.W.
      • Jellinger P.S.
      A critique of the 2012 ADA/EASD position statement (Letter to the Editor).

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        • et al.
        Patterns of medication initiation in newly diagnosed diabetes mellitus: quality and cost implications.
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        • Davidson M.B.
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        Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).
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        • Jellinger P.S.
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        Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control.
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      Linked Article

      • Patterns of Medication Initiation in Newly Diagnosed Diabetes Mellitus: Quality and Cost Implications
        The American Journal of MedicineVol. 125Issue 3
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          Six oral medication classes have been approved by the Food and Drug Administration for the treatment of type 2 diabetes. Although all of these agents effectively lower blood glucose, the evidence supporting their impact on other clinical events is variable. There also are substantial cost differences between agents. We aimed to evaluate temporal trends in the use of specific drugs for the initial management of type 2 diabetes and to estimate the economic consequences of non-recommended care.
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