Review of 2018 ADA guidelines: dyslipidemia in the context of diabetes

ADA recommendations are released each January. Below is a succinct ACP review of guidelines in screening, treatment goals, lifestyle intervention, and drug approach to dyslipidemia in the setting of diabetes mellitus. LDL-cholesterol is still a main target. Charts depict indications and doses of statins, the mainstay therapy to diabetic lipid disorders.

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Also see:

Lipid guidelines related posts

Dyslipidemia related posts


Annals of Internal Medicine

ADA Guidelines

April 2018

 

Lifestyle:

  • Lifestyle modification focusing on weight loss (if indicated); the reduction of saturated fat, trans fat, and cholesterol intake; increase of dietary n-3 fatty acids, viscous fiber, and plant stanols/sterols intake; and increased physical activity should be recommended to improve the lipid profile in patients with diabetes.
  • Intensify lifestyle therapy and optimize glycemic control for patients with elevated triglyceride levels ≥150 mg/dL and/or low HDL cholesterol <40 mg/dL for men, <50 mg/dL for women.

Patients should replace saturated fats with unsaturated fats rather than refined carbohydrates. Randomized trials do not support use of n-3 fatty acid supplements for primary or secondary prevention of ASCVD. Randomized trials show that a Mediterranean-style diet rich in polyunsaturated and monounsaturated fats can improve glycemic control and lipid levels.

 

Monitoring:

  • In adults not taking statins or other lipid-lowering therapy, it is reasonable to obtain a baseline lipid profile at the time of diabetes diagnosis, at an initial medical evaluation, and every 5 years thereafter if under the age of 40 years, or more frequently if indicated.
  • Obtain a lipid profile at initiation of statins or other lipid-lowering therapy, 4–12 weeks after initiation or a change in dose, and annually thereafter as it may help to monitor the response to therapy and inform adherence.

 

Statin Treatment:

  • For patients of all ages with diabetes and ASCVD, high-intensity statin therapy should be added to lifestyle therapy.
  • For patients with diabetes aged <40 years with additional ASCVD risk factors, the patient and provider should consider using moderate-intensity statin in addition to lifestyle therapy.
  • For patients with diabetes aged 40–75 years and >75 years without ASCVD, use moderate-intensity statin in addition to lifestyle therapy.
  • In clinical practice, providers may need to adjust the intensity of statin therapy based on individual patient response to medication (e.g., side effects, tolerability, LDL-cholesterol levels, or percent LDL reduction on statin therapy). For patients who do not tolerate the intended intensity of statin, the maximally tolerated statin dose should be used.
  • For patients with diabetes and ASCVD, if LDL cholesterol is ≥70 mg/dL on maximally tolerated statin dose, consider adding additional LDL-lowering therapy, such as ezetimibe or PCSK9 inhibitor, after considering the potential for further ASCVD risk reduction, drug-specific adverse effects, and patient preferences. Ezetimibe may be preferred due to lower cost.

Given that clinical trials show beneficial effects of statin therapy on ASCVD outcomes in patients with and without coronary heart disease, statins are the drug of choice for LDL cholesterol lowering and cardioprotection. High-intensity statin therapy achieves a reduction of approximately 50% in LDL-C level, and moderate-intensity regimens achieve reductions of 30-50%. Low-dose statin therapy is generally not recommended in patients with diabetes but is sometimes the only dose that a patient can tolerate.

For PRIMARY prevention in patients aged 40-75 years without clinical ASCVD, moderate-dose statin therapy is recommended, although high-intensity therapy may be considered for certain patients with additional ASCVD risk factors. Few persons older than 75 years were enrolled in trials of statins; however, the absolute benefits of treatment for them may exceed the benefits for younger persons because increasing age generally confers higher risk for ASCVD. Moderate-intensity statin therapy is recommended in patients with diabetes who are older than 75 years, with downward titration of the dose if needed on the basis of risk–benefit profile assessments.

Little evidence from clinical trials exists for patients with type 2 diabetes who are younger than 40 years and for those with type 1 diabetes of any age. Patients younger than 40 years have lower risk for cardiovascular events over a 10-year horizon; however, their lifetime risk for ASCVD and myocardial infarction, stroke, or cardiovascular death is high. For patients younger than 40 years with type 2 diabetes and other ASCVD risk factors and for patients with type 1 diabetes and other ASCVD risk factors, we recommend that the patient and the health care provider discuss relative benefits and risks and consider use of moderate-intensity statin therapy.

For SECONDARY prevention in patients with ASCVD, high-intensity statin therapy is recommended. Recent randomized trials investigating the benefits of adding nonstatin agents, like ezetimibe and PCSK9 inhibitors, to statin therapy showed reduced risk for ASCVD events with the added therapy that seemed to be related to the degree of further LDL cholesterol lowering.

Ezetimibe is indicated to reduce LDL cholesterol levels in patients with hyperlipidemia, and the PCSK9 inhibitors evolocumab and alirocumab have been approved as adjunctive therapy for patients with ASCVD or familial hypercholesterolemia who are receiving maximum tolerated statin therapy but require additional lowering of LDL cholesterol levels.

 

Triglyceride Treatment:

  • For patients with fasting triglyceride levels ≥500 mg/dL, evaluate for secondary causes of hypertriglyceridemia and consider medical therapy to reduce the risk of pancreatitis.

Hypertriglyceridemia should be addressed with dietary and lifestyle changes, including abstinence from alcohol. Severe hypertriglyceridemia >1000 mg/dL  may warrant pharmacologic therapy like fibric acid derivatives, fish oil, or both, to reduce risk for acute pancreatitis.

 

Combination Therapy:

  • Combination therapy (statin/fibrate) has NOT been shown to improve ASCVD outcomes and is generally NOT recommended.
  • Combination therapy (statin/niacin) has NOT been shown to provide additional cardiovascular benefit above statin therapy alone, may increase the risk of stroke with additional side effects, and is generally NOT recommended.

Combination therapy with a statin and a fibrate is associated with increased risk for abnormal aminotransferase levels, myositis, and rhabdomyolysis. In the ACCORD trial, the combination of fenofibrate and simvastatin did not reduce the rate of fatal cardiovascular events, nonfatal myocardial infarction, or nonfatal stroke compared with simvastatin alone.

Combination therapy with a statin and extended-release niacin was evaluated in a trial that was halted early due to lack of efficacy on the primary composite outcome (cardiac death, nonfatal myocardial infarction, ischemic stroke, hospitalization for an acute coronary syndrome, or symptom-driven coronary or cerebral revascularization) and a possible increase in ischemic stroke in patients receiving combination therapy.

 

Statin Concerns:

Several studies have shown that statin use is associated with a modestly increased risk for incident diabetes; the increased risk may be limited to persons with diabetes risk factors. In one study, the absolute risk increase was small (1.2% of participants receiving placebo and 1.5% receiving rosuvastatin developed diabetes over 5 years of follow-up), and the cardiovascular event rate reduction with statins outweighed the risk for diabetes, even for patients at the highest risk for diabetes.

Concern that statins or other lipid-lowering agents might cause cognitive dysfunction or dementia should not preclude their use in patients with diabetes who are at high risk for ASCVD. A recent systematic review of the FDA's postmarketing surveillance databases that evaluated cognition in patients receiving statins found that published data do not show an adverse effect of statins on cognition.

 
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