The newly revised type 2 diabetes treatment algorithm released jointly by the American Diabetes Association and the European Association for the Study of Diabetes is designed to help clarify decisions about current therapeutic options.
“The major target and intent of the consensus algorithm was to help the busy nonspecialists, who provide care for the vast majority of patients with type 2 diabetes, to select the most effective, acceptable, and cost-effective interventions from the now numerous choices available,” Dr. David M. Nathan said in an interview. Dr. Nathan is chair of the consensus panel that developed the recommendations and director of the general clinical research center and of the diabetes center at Massachusetts General Hospital, Boston.
But the document did raise some questions. The algorithm includes “several surprising recommendations which are somewhat inconsistent with the treatment regimens used by many endocrinologists and other treating physicians… including the rejection of DPP-4 inhibitors, the elimination of rosiglitazone despite increasing trial safety data, and relegation of the thiazolidinedione class (pioglitazone) to ‘less well validated’ tier 2. Many believe that TZDs have been well validated in relation to A1c lowering and, in particular, durability, and DPP-4 inhibitors in combination with metformin offer robust and safe A1c lowering,” Dr. Paul Jellinger said in an interview. “The patient in front of you requires individualized treatment that may not be consistent with this or perhaps any other algorithm. One size just doesn't fit all.” Dr. Jellinger, who was speaking only for himself, is past president of the American Association of Clinical Endocrinologists.
Even though a disclaimer states that it is not official organizational policy, “this consensus statement from both groups will be viewed by the casual reader, managed care and most everyone else as official ADA recommendations for treatment,” he added, noting that it has the potential to complicate ongoing care.
The algorithm also does not discuss postprandial glucose control, noted Dr. Jaime Davidson, clinical professor of medicine in the division of endocrinology at the University of Texas Southwest Medical Center, in Dallas. And he agrees that DPP-4 inhibitors should be considered first-tier treatment. “They have good data; they look very safe.”
The consensus statement, published online in Diabetes Care and in Diabetologia, updates the treatment algorithm first published in 2006, taking into account newer medications and recent scientific data on previously recommended drugs (Diabetes Care 2008 Oct. 22 [doi:10.2337/dc08–9025]; Diabetologia 2008 Oct. 22 [doi:10.1007/s00125–008–1157-y]).
The algorithm emphasizes the achievement and maintenance of near normoglycemia (hemoglobin A1c [HbA1c] less than 7%) and initial therapy with lifestyle changes and metformin therapy. The guidelines also focus on adding medications and changing regimens when treatment goals are not achieved or sustained, and the early addition of insulin therapy in patients who do not meet goals.
“Our consensus is that an HbA1c level of 7% or greater should serve as a call to action to initiate or change therapy with the goal of achieving an HbA1c level of less than 7%,” the consensus group wrote. When HbA1c levels are 7% or greater, interventions should be changed at as rapid a pace as titration of medications allows.
The algorithm classifies treatments as tier 1 or tier 2 interventions. Tier 1 interventions are well-validated core therapies that are the most effective and cost-effective for achieving glycemic goals.
According to the tier 1 algorithm, the first step in treating newly diagnosed type 2 diabetes should be to begin lifestyle changes. “Lifestyle interventions to improve glucose and to promote weight loss … should remain an underlying theme throughout the management of type 2 diabetes, even after medications are used,” the consensus group wrote.
But because lifestyle changes are not enough to achieve or maintain goals in most type 2 patients, metformin therapy should be started concurrently with lifestyle intervention at diagnosis, unless there are contraindications, they wrote.
When lifestyle changes and the maximal tolerated dose of metformin do not achieve or maintain glycemic goals, the algorithm recommends that another medication—insulin or a sulfonylurea—be added, either within 2–3 months of the initiation of therapy or at any time when the target HbA1c level is not achieved.
That part of the algorithm presents a problem for Dr. Davidson. The algorithm “says if the patient's A1c reaches 7% or higher for patients already on oral anti-diabetic therapy, when you go for insulin you need to use basal insulin,” he said. “Show me one trial where A1c was 7% and they started basal insulin; I've never seen one. We start insulin therapy most of the time around 8.5%, and you get down only to 7% as an average. If you try to get below 7% you increase risk of hypoglycemia significantly.” Instead, using prandial insulin before breakfast would be a better approach, he said.
When lifestyle changes, metformin, and either sulfonylurea therapy or basal insulin are still not sufficient to achieve target glycemia, the algorithm says the next step is to start or intensify insulin therapy.
Tier 2 therapies are less well validated but may be added to lifestyle changes and metformin in selected situations. These include pioglitazone or the glucagonlike peptide 1 agonist exenatide. “Rosiglitazone is not recommended,” the authors wrote.
Dr. Nathan and each of his coauthors acknowledged several significant financial relationships with pharmaceutical companies. Dr. Jellinger is on the speakers' bureau for several pharmaceutical companies, including Novo Nordisk, Amylin Lilly, and Takeda.
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