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Integrate Incretins Into Type 2 Diabetes Therapy


 

PHILADELPHIA — When physicians are initiating therapy for type 2 diabetes, they should consider integrating incretins into their medication arsenal, said Dr. Elliot Sternthal, clinical director of diabetes services at Boston Medical Center.

The injectable incretinomimetic exenatide, the injectable amylinomimetic pramlintide, and the dipeptidyl peptidase-4 inhibitor sitagliptin provide additional options for physicians in diabetes-modifying therapy. These compounds would also be attractive if they were to gain an indication for use in prediabetes because of their potential to prevent the progression of islet cell dysfunction seen in type 2 diabetes, he said.

But be sure to correctly identify the metabolic “stage” of diabetes patients based on their hemoglobin A1c levels, fasting blood sugar, 2-hour postprandial blood sugar, and renal and hepatic status, Dr. Sternthal said at Endocrinology in the News, sponsored by Boston University, INTERNAL MEDICINE NEWS and FAMILY PRACTICE NEWS.

For type 2 diabetes patients with mild hyperglycemia or an HbA1c between 6% and 7%, the options for initiating treatment include an a-glucosidase inhibitor, metformin, thiazolidinedione (TZD), and sitagliptin. Advanced therapy could include combinations of these drugs, such as metformin plus a TZD.

For patients with moderate hyperglycemia with an HbA1c of 7%-8%, initial therapy options include an a-glucosidase inhibitor, metformin, TZD, sitagliptin, meglitinide, low-dose sulfonylurea, TZD plus metformin, or sitagliptin plus metformin. The use of metformin with sita- gliptin may actually increase the release of incretins, Dr. Sternthal said.

For later stages of moderate hyperglycemia, consider sulfonylurea plus either metformin or TZD, for example.

For patients with moderately severe hyperglycemia, or an HbA1c of 8%-9%, combinations are likely to be the first-line approach. Physicians can consider the use of high-dose sulfonylurea or metformin alone. However, initial therapy is likely to involve two-drug combinations such as metformin plus TZD, TZD plus sita- gliptin, or sulfonylurea plus exenatide.

For advanced therapy, consider three-drug combinations such as sulfonylurea plus metformin plus TZD.

You have to pick and choose what's best for your patient, said Dr. Sternthal, who is on the speakers bureau for Amylin, AstraZeneca, Eli Lilly & Co., and Merck.

In cases of severe hyperglycemia, with an HbA1c of greater than 9%, there is no role for monotherapy, Dr. Sternthal said. Initial therapy may even begin with the use of three agents, he said. Possible initial courses include metformin plus TZD plus exenatide, metformin plus TZD plus sitagliptin, and sulfonylurea plus metformin plus TZD.

The number of incretins available to treat type 2 diabetes is set to expand in the near future, said Dr. Marie E. McDonnell, director of inpatient diabetes at Boston Medical Center.

Liraglutide, a once-weekly formulation of exenatide (Byetta), is currently under investigation; exenatide also is being investigated for use in combination insulin. A dipeptidyl peptidase-4 (DPP-4) inhibitor, vildagliptin, is on the way. And glucagon receptor antagonists are also being studied, Dr. McDonnell said at the meeting.

But there is still no alternative to insulin therapy, said Dr. McDonnell, who is on the speakers bureau for Sanofi Aventis.

“Do not lose sight of insulin-deficient patients—they need you,” she said.

FAMILY PRACTICE NEWS and INTERNAL MEDICINE NEWS are published by the International Medical News Group, a division of Elsevier.

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