Applied Evidence

What’s new in type 2 diabetes?

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References

If a patient is taking multiple BP medications, one or more should be taken at bedtime.4 Administering an antihypertensive at night results in better ambulatory BP control and reduces cardiovascular mortality.12

CASE JR is on maximal doses of 2 antihypertensive agents, and his BP is 132/70 mm Hg. His physician must individualize care and decide if adding a third agent is worth the risk of another medication when clear benefit has not been demonstrated. It is reasonable to continue his current regimen with the exception of changing his lisinopril dose to the evening and reassessing his BP control at his next visit.

Cholesterol

Controlling LDL remains the top priority of T2DM lipid management. In addition to lifestyle changes, statins are the primary means of achieving LDL goals. All patients with overt CVD should receive a statin.4 Also prescribe a statin for patients with diabetes who do not have CVD but who are older than 40 and have one or more cardiac risk factors, regardless of their baseline LDL cholesterol.4 The recommended LDL goal in T2DM patients continues to be <100 mg/dL. However, <70 mg/dL is a reasonable goal for those with known CVD.13

Using additional lipid-lowering agents besides a statin may improve cholesterol numbers, but not CVD outcomes. In the ACCORD study, adding fenofibrate to simvastatin did not decrease fatal cardiovascular events or nonfatal myocardial infarction and stroke compared with simvastatin given alone.14 The AIM-High study showed no difference in cardiovascular outcomes and a possible increase in ischemic stroke with combination niacin and statin compared with statin therapy alone.15 For now, lifestyle changes and statins remain the ideal modalities to achieve LDL goals.

CASE Should a statin be initiated for our patient? Since JR is over 40 without known CVD and has a cardiac risk factor of hypertension, he should be started on statin therapy regardless of his baseline LDL (90 mg/dL), which is already at goal (<100 mg/dL).

Drug management

Let the glycemic goal for each patient guide your medication management. The 2012 ADA recommendation for most adults is an A1C of <7%.4 More strict control (A1C <6.5%) may be appropriate for certain individuals with a long life expectancy, short duration of diabetes, and no significant micro- or macrovascular disease.4 Less strict control (A1C <8%) may be appropriate for individuals with significant comorbidities, shorter life expectancy, severe hypoglycemia, or long-standing T2DM that’s been difficult to control despite multiple medications, including insulin.4

Individualize treatment. In April 2012, the ADA released a position statement encouraging a patient-centered approach to managing hyperglycemia in T2DM.16 This statement contains a new treatment algorithm (available at: http://care.diabetesjournals.org/content/early/2012/04/17/dc12-0413.full.pdf+html) that is less prescriptive than the previous 2009 algorithm and balances provider judgment, patient preference, and susceptibility to adverse effects in order to attain an individualized A1C target.16 Although a comprehensive review of T2DM pharmacotherapy is beyond the scope of this article, we will discuss the importance of metformin, familiarize prescribers with incretin-based therapy, and highlight recent safety concerns regarding thiazolidinediones (TZDs).

Metformin is first line. The 2012 ADA guidelines recommend prescribing metformin at the time of diagnosis of T2DM, in addition to advising lifestyle changes.4,16 The American College of Physicians (ACP) also recommends metformin as the first agent in diabetes management, citing the benefits of weight loss, improved lipid profiles, and decreased cardiovascular mortality.17 Adding a second medication to metformin at the time of diagnosis may be considered if the initial A1C value is >9%.16 Because robust comparative trials are lacking, the selection of additional medications beyond metformin depends on a patient-centered approach, with consideration of efficacy, adverse effect profile, and cost.16 The TABLE provides a succinct review of the key properties of diabetic medications that clinicians may discuss with their patients. All of the listed agents are valid second-line treatments, and you should select one based on the individual’s needs.

Incretin-based therapy. Among newer antihyperglycemic agents, incretins have drawn much attention and thus warrant special focus. The emphasis on these agents should not be interpreted as an implied endorsement for their second-line use. There are 2 main classes: dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) agonists. Both act on the gut peptide GLP-1 to enhance glucose-stimulated insulin secretion and glucagon suppression.16

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