Update on the Canadian Diabetes Association 2008 clinical practice guidelines

Targets for glycemic control

The new guidelines recommend a target hemoglobin A_1c (HbA_1c) level of ≤ 7% for all patients with diabetes (A). A more aggressive target of ≤ 6.5% can be considered for some patients to help prevent microvascular complications, but this benefit must be weighed against an increase in mortality in patients at very high risk of cardiovascular (CV) events (A).

The benefit of achieving the target HbA_1c level of ≤7% for microvascular risk reduction is well established.3 The 2003 CPGs also suggested a more aggressive target of ≤6%, but 2 recent randomized controlled trials showed no macrovascular benefit to this target. The ACCORD trial demonstrated that a therapeutic strategy to lower the level of HbA_1c to <6% in high-risk patients did not reduce the risk of macrovascular disease and, in fact, was associated with a small increase in mortality.4 The ADVANCE trial did not show this increased mortality, but it also did not demonstrate macrovascular benefit of lowering the HbA_1c level below 6.5%; it did, however, show a reduction in nephropathy in the intensive-control group.5 In contrast, the posttrial monitoring of the United Kingdom Prospective Diabetes Study (UKPDS-PTM) demonstrated a reduction in myocardial infarction and all-cause mortality in the subgroup with intensive glycemic control after a 10-year posttrial follow-up.6 The key differences between the UKPDS-PTM and the ACCORD and ADVANCE trials are UKPDS-PTM’s early intervention and longer follow-up. This suggests that earlier intervention has lasting benefit but that a target HbA_1c level of ≤7% is more appropriate in patients at high risk of vascular events who have had diabetes for a long time.

Monitoring glycemic control

Patients with type 2 diabetes taking once-daily insulin and oral antihyperglycemic agents should monitor their blood glucose at least once a day at different times (D), or more often if they are on multiple doses of insulin (C). Because there is contradictory evidence about the benefit of self-monitoring of blood glucose for patients who are not taking insulin, self-monitoring should be individualized according to the type of treatment and level of control (D).

Pharmacologic management of type 2 diabetes

As more antihyperglycemic agents become available, careful consideration should be given to their advantages and disadvantages. Figure 1 summarizes the key points from the guidelines. Metformin remains the initial drug for type 2 diabetes, but the guidelines now support its use in all people with diabetes, irrespective of body weight (D). When glycemic targets are not met with metformin alone, 1 or more agents from a different class should be added to metformin. The choice of second-line agents depends on the desired (and undesired) characteristics of the treatment. The incretin agent, dipeptidyl peptidase-4 inhibitor, is a new option. In the presence of marked hyperglycemia (HbA_1c ≥ 9%), the 2008 CPGs recommend starting combination pharmacologic therapy immediately, concurrent with lifestyle changes (D). When basal insulin is added to antihyperglycemic agents, the guidelines recommend considering insulin analogues (eg, insulin detemir or insulin glargine) instead of neutral protamine Hagedorn (NPH) to reduce risk of nocturnal or symptomatic hypoglycemia (A).

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Figure 1

Pharmacologic management of type 2 diabetes

Cardiovascular risk assessment

The degree of benefit of medical intervention is based on patients’ absolute risk of CV events, with higher-risk patients deriving greater benefit.8 Thus, identifying those at high risk can ensure that those who are most likely to benefit will receive treatment. Age is among the strongest predictors of risk, so the CDA recommends that men 45 years and older and women 50 years and older should be considered high risk. Patients below these age cutoffs, but meeting any 1 of the other important CV risk factors, should also be considered high risk.

Vascular protection

People with diabetes develop vascular disease approximately 15 years earlier than people without diabetes.9 The concept of vascular protection was introduced in the 2003 CPGs, but it has been further stratified in the 2008 version, owing to evidence that shows a comprehensive multifactorial approach to vascular protection substantially reduces complications.10,11 All patients with diabetes should receive interventions to reach target blood pressure (BP) of < 130/80 mm Hg and HbA_1c levels of ≤ 7%, to stop smoking, and to maintain healthy diets, physical activity, and healthy body weight. On top of these interventions, those found to be at high risk should be prescribed angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs),12 lipid-lowering medications (particularly statins), and possibly acetylsalicylic acid (ASA). It is important to note that ARBs are now included in the CPGs as an alternative to ACE inhibitors. Specific reference to statins is also new and reflects the growing literature on the benefits of these medications for high-risk groups.13,14 Recommendations regarding ASA have also been modified, because ASA therapy has been shown to have less of a cardioprotective effect in patients with diabetes than in those without diabetes, and to have no benefit in primary prevention.15,16 Thus, the 2008 CPGs state that low-dose ASA therapy (81 to 325 mg) could be considered in people with stable CVD (D) but clinical judgement should be exercised regarding its use in primary prevention (D).

Treatment of hypertension

Strict control of BP improves morbidity and mortality in patients with diabetes.3,17–19 The CDA recommends that BP be measured at every visit and hypertension be diagnosed according to the national hypertension guidelines (www.hypertension.ca/chep). Treatment targets remain systolic BP < 130 mm Hg (C) and diastolic BP < 80 mm Hg (B). Clinical trials have shown that multiple medications and titrations are required to achieve these targets.18,20 A summary of recommended first-line and combination medications is provided in Table 2, but it is important to note that ACE inhibitors and ARBs are given special consideration as first-line treatment agents because of their renal benefits (D)12 and that α-blockers are not recommended as first-line agents for patients with diabetes (A).

Treatment of dyslipidemia

Dyslipidemia is a well-recognized risk factor for CVD. Fasting lipid levels should be measured at the time of diagnosis and every 1 to 3 years afterward (D). The primary target of therapy is the low-density lipoprotein cholesterol level (LDL-C) (≤ 2.0 mmol/L in patients at high risk [A]); the secondary target is the ratio of total cholesterol (TC) to high-density lipoprotein cholesterol (HDL-C) (< 4 mmol/L in patients at high risk [D]). Statins are the first-line treatment for dyslipidemia in patients with diabetes. If targets cannot be achieved with statins alone, combination therapy with ezetimibe, fibrate, or niacin can be considered (B), although there are no completed trials demonstrating clinical outcomes. Hypertriglyceridemia (triglyceride levels > 10.0 mmol/L) should be treated with fibrates to reduce the risk of pancreatitis (D).

Screening for coronary artery disease

Asymptomatic cardiac ischemia is common among those with diabetes. Many patients who present with myocardial infarction have no preceding symptoms. To identify those with established coronary artery disease in the absence of symptoms, the 2008 CPGs recommend that baseline electrocardiograms be conducted in all individuals older than 40 years of age (D).