PART 3: MANAGING CHOLESTEROL AND CONTROLLING LIPIDS

Part Three: Managing Cholesterol and Controlling Lipids (The “C” of ABCS)

Lipid management is a central component of diabetes management, and lipid goals should be attained though a holistic management plan that includes lifestyle modifications (e.g., weight management, physical activity, MNT) and pharmacotherapy. As noted previously, elevated blood glucose is linked to numerous atherogenic abnormalities, and physicians/clinicians should expect to manage lipids as part of most diabetes interventions.

Low-Density Lipoprotein (LDL). LDL is the dominant cholesterol carrier82 and has consequently become the primary focus of dyslipidemia management. As such, recommendations for managing LDL cholesterol (LDL-C) levels are supported by a large body of evidence. When supplementing lifestyle modifications with pharmacotherapy for LDL-C, the ADA is unequivocal as to the starting point. In its 2018 Standards of Medical Care in Diabetes, the Association notes that statins are “the drugs of choice for LDL cholesterol [LDL-C] lowering and cardioprotection.”17 The efficacy and safety of statins to reduce LDL-C and prevent vascular events in patients with diabetes has been established for individuals at high-risk for ASCVD83 and for those at low- to medium-risk,84, 85 independent of gender.86 A recent meta-analysis of 49 trials (n=312,975) that compared statins to non-stain therapies suggests that statins and established non-statin therapies that act via upregulation of LDL receptor expression (e.g., diet, bile acid sequestrants, ileal bypass, and ezetimibe) to reduce LDL-C were associated with similar relative risks of major vascular events per unit change in LDL-C.87 Moreover, lower LDL-C levels were associated with lower rates of these events. The ADA recommends initiating and intensifying statin therapy based on CVD risk profile (Table 7), with the caveat that statin therapy is contraindicated in pregnancy (Evidence Rating: B). A ten-year ASCVD risk estimator developed by the American Heart Association and the American College of Cardiology is available at http://tools.acc.org/ASCVD-Risk-Estimator/.

 

Table 7. ADA Recommendations for Statin and Combination Treatment in Adults with Diabetes17

Age (years)

 ASCVD

Recommended statin intensity and combination treatment (in addition to lifestyle therapy)

< 40

No

None†

Yes

High

  • If LDL-C > 70 mg/dL despite maximally tolerated statin dose, consider adding additional LDL-lowering therapy (e.g., ezetimibe or PCSK9 inhibitor).#

> 40

No

Moderate‡

Yes

High

  • If LDL-C > 70 mg/dL despite maximally tolerated statin dose, consider adding additional LDL-lowering therapy (e.g., ezetimibe or PCSK9 inhibitor).

For patients who do not tolerate the intended intensity of statin, the maximally tolerated statin dose should be used.

†Moderate-intensity statin may be considered based on risk-benefit profile and presence of ASCVD risk factors (e.g., LDL-C > 100 mg/dL, high blood pressure, smoking, chronic kidney disease, albuminuria, and family history of premature ASCVD).

‡High-intensity statin may be considered based on risk-benefit profile and presence of ASCVD risk factors.

#Adults aged < 40 years with prevalent ASCVD were not well represented in clinical trials of non-statin–based LDL reduction. Before initiating combination lipid-lowering therapy, consider the potential for further ASCVD risk reduction, drug-specific adverse effects, and patient preferences.

 

The ADA recommends high-intensity statin therapy (Table 8) for all individuals with diabetes and ASCVD and moderate-intensity therapy for individuals 40 years and older with no ASCVD (although high-intensity therapy may be considered on an individual basis in the context of additional ASCVD risk factors).17 In general, high-intensity statin therapy will reduce LDL-C by approximately 50%, as compared to a 30-50% reduction with moderate-intensity doses. A lipid profile (e.g., total cholesterol, LDL-C, HDL-C, and triglycerides) is commonly used to monitor stain therapy for efficacy and for patient adherence. Timing of lipid panels for individuals with diabetes is influenced by patient-related factors and clinical judgment, but the ADA suggests obtaining a lipid panel at the time of diagnosis, at the initial medical evaluation, and at least once every five years thereafter, as well as immediately before initiating stain therapy (Evidence Rating: E). Combination therapy with a statin and ezetimibe or a PCSK9 inhibitor may be warranted to lower LDL-C in individuals with diabetes and a history of ASCVD who cannot tolerate high-intensity statin therapy.

 

Table 8. High-Intensity and Moderate-Intensity Statin Therapy (Once-Daily Dosing)17

High-Intensity

Moderate-Intensity

  • Atorvastatin 40-80 mg
  • Rosuvastatin 20-40 mg
  • Atorvastatin 10-20 mg
  • Rosuvastatin 5-10 mg
  • Simvastatin 20-40 mg
  • Pravastatin 40-80 mg
  • Lovastatin 40 mg
  • Fluvastatin XL 80mg
  • Pitavastatin 2-4 mg

 

Other Lipid Targets. Persons with diabetes often present with abnormalities in lipid targets other than LDL, including HDL-C and triglyceride levels. Mounting evidence suggests that elevated triglyceride levels may be a causal risk factor for ASCVD, low-grade inflammation, and mortality.88 Lifestyle therapy (e.g., diet, physical activity, weight reduction) is the cornerstone of managing mild-to-moderate hypertriglyceridemia (triglycerides of 150-999 mg/dL).17, 82 It should be noted that the literature to support the use of drugs to target HDL-C and triglycerides is less robust than that for statin therapy, and the ADA does not recommend combination therapies with statins plus niacin or a fibrate due to potential side effects and a lack of evidence supporting efficacy on major ASCVD outcomes (Evidence Rating: A).17 Table 9 summarizes ADA recommendations for cholesterol management in individuals with diabetes.

 

Table 9. ADA Recommendations for Managing Lipids17

Recommendation

Level of Evidence*

Lifestyle modification focusing on weight loss (if indicated); the reduction of saturated fat, trans fat, and cholesterol intake; increase of dietary omega-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.

A

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).

C

For patients of all ages with diabetes and ASCVD, high-intensity statin therapy should be added to lifestyle therapy.

A

For patients with diabetes aged <40 years with additional ASCVD risk factors, the patient and provider should consider using moderate- or high-intensity statin and lifestyle therapy.

C

For patients with diabetes aged 40–75 years without ASCVD, use moderate-intensity statin with lifestyle therapy.

A

For patients with diabetes aged >75 years without ASCVD, use high-intensity statin with lifestyle therapy.

B

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-C 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.

E

For patients with diabetes and ASCVD, if LDL-C is > 70 mg/dL on the maximally-tolerated statin dose, consider adding additional LDL-lowering therapy (such as ezetimibe or a PCSK9 inhibitor) after evaluating the potential for further ASCVD risk reduction, drug-specific adverse effects, and patient preferences. Ezetimibe may be preferred due to lower cost.

A

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.

C

Combination therapy (statin/fibrate) has not been shown to improve ASCVD outcomes and is generally not recommended.

A

Combination therapy (statin/niacin) has not been shown to provide additional cardiovascular benefit above statin therapy alone, may increase the risk of stroke, and is not generally recommended.

A

Statin therapy is contraindicated in pregnancy.

B

*The ADA evidence grading system for these recommendations is provided in Table 2.47

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