387 - Diabetes Standards of Care 2021 – Part 2: Medications

From the Guidelines and the American Diabetes Association (ADA)

1) ADA Diabetes Pharmacotherapy Standards of Care 2021

The Standards are developed by the ADA’s multidisciplinary Professional Practice Committee, which comprises physicians, diabetes educators, and other expert diabetes healthcare professionals. The Standards include the most current evidence-based recommendations for diagnosing and treating adults and children with all forms of diabetes. The ADA’s grading system uses A, B, C, or E to show the evidence level that supports each recommendation. This is the 2^nd part of a two-part summary.

Pharmacotherapy Recommendations – Prediabetes:

• Metformin therapy for prevention of T2D should be considered in those with prediabetes, especially for those with BMI >35, age <60, and/or hx of GDM. A

Pharmacotherapy Recommendations- Type 2 Diabetes (T2D):

• Metformin is the preferred initial pharmacologic agent for the treatment of T2D. A
• Once initiated, metformin should be continued as long as it is tolerated and not contraindicated; other agents, including insulin, should be added to metformin. A
• The early introduction of insulin should be considered if there is evidence of ongoing catabolism (weight loss), if symptoms of hyperglycemia are present, or when A1C levels (>10) or blood glucose levels (≥300) are very high. E
• Among patients with T2D who have established atherosclerotic CVD (ASCVD) or indicators of high risk, established kidney disease, or HF, a sodium–glucose cotransporter 2 (SGLT2) inhibitor or glucagon-like peptide 1 (GLP-1) receptor agonist with demonstrated CVD benefit is recommended. A
• A GLP-1 receptor agonist is preferred to insulin when possible. A
• Treatment intensification for patients not meeting goals should not be delayed. A
• Clinicians should be aware of the potential for overbasalization with insulin therapy. Clinical signals that may prompt evaluation of overbasalization include basal dose more than ∼0.5 IU/kg, high bedtime-morning or post-preprandial glucose differential, hypoglycemia (aware or unaware), and high variability. Indication of overbasalization should prompt reevaluation to further individualize therapy. E

Hypertension/Blood Pressure Control in T2D – Recommendations:

• Patients with blood pressure ≥140/90 should, in addition to lifestyle therapy, have initiation of pharmacologic therapy to achieve blood pressure goals. A
• ACE inhibitors or ARBs are recommended first-line therapy with CAD. A
• Combinations of ACE inhibitors and ARBs and combinations of ACE inhibitors or ARBs with direct renin inhibitors should not be used. A
• An ACE inhibitor or ARB, at the maximum tolerated dose indicated for blood pressure treatment, is the recommended first-line treatment for HTN if urinary albumin-to-creatinine ratio (UACR) ≥300 A or 30–299. B 
• For patients treated with an ACE inhibitor, ARB, or diuretic, serum eGFR and serum potassium levels should be monitored at least annually. B
• If not meeting BP goals with three classes of medications (including a diuretic), mineralocorticoid receptor antagonist therapy should be considered. B

Statin Treatment in T2D – Recommendations:

Primary Prevention:

• If aged 40–75 years without ASCVD, use moderate-intensity statin therapy. A
• If aged 20–39 years with additional ASCVD risk factors, it may be reasonable to initiate statin therapy in addition to lifestyle therapy. C
• If at higher risk, especially with multiple ASCVD risk factors or aged 50–70 years, it is reasonable to use high-intensity statin therapy. B
• If 10-year ASCVD risk > 20%, it may be reasonable to add ezetimibe to maximally tolerated statin therapy to reduce LDL cholesterol levels by 50% or more. C
• If aged >75 years and already on statin therapy, it is reasonable to continue. B
• If aged >75 years, may be reasonable to initiate a statin after discussion of potential benefits and risks. C

Secondary Prevention:

• If established ASCVD, use high-intensity statin therapy. A
• If very high risk using specific criteria and LDL ≥70 on maximally tolerated statin dose, consider adding additional LDL-lowering therapy (such as ezetimibe or PCSK9 inhibitor). A Ezetimibe may be preferred due to lower cost.
• If intended statin intensity is not tolerated, use maximally tolerated dose. E
• Statin plus fibrate combination therapy is not recommended. A
• Statin plus niacin combination therapy is not recommended. A

Antiplatelet Agents and T2D – Recommendations:

• Aspirin therapy (75–162 mg/day) may be considered as a primary prevention strategy in those with diabetes who are at increased CV risk, after a comprehensive discussion on the benefits versus the comparable increased risk of bleeding. A

Patients with T2D and established ASCVD:

• If established ASCVD or established kidney disease, an SGLT2 inhibitor or GLP-1 receptor agonist with demonstrated CVD benefit is recommended as part of the comprehensive CV risk reduction and/or glucose-lowering regimens. A
• If established ASCVD, multiple ASCVD risk factors, or diabetic kidney disease (DKD), an SGLT2 inhibitor with demonstrated CV benefit is recommended. A
• If established ASCVD or multiple risk factors for ASCVD, a GLP-1 receptor agonist with demonstrated CV benefit is recommended. A
• If established HF with reduced ejection fraction (HFrEF), an SGLT2 inhibitor with proven benefit in this patient population is recommended. A
• If known ASCVD, particularly CAD, ACE-I or ARB therapy is recommended. A
• HFrEF treatment should include a β-blocker with proven CV outcomes benefit. A
• If stable HF, metformin may be continued for glucose lowering if eGFR remains >30 but should be avoided in unstable or hospitalized patients with HF. B

Patients with T2D and CKD/DKD (diabetic kidney disease) – Recommendations:

• Consider use of an SGLT2 inhibitor in patients with an eGFR ≥30 and urinary albumin >300. A
• Consider use of SGLT2 inhibitors additionally for CV risk reduction when eGFR and urinary albumin creatinine are ≥30 or >300, respectively. A
• If CKD at increased risk for CV events, use of a GLP-1 agonist reduces renal end points, primarily albuminuria, progression of albuminuria, and CV events. A
• Optimize blood pressure control to reduce the risk or slow the progression of CKD. A
• Do not discontinue renin-angiotensin system blockade for minor increases in serum creatinine (<30%) in the absence of volume depletion. A
• For people with nondialysis-dependent CKD, dietary protein intake should be ∼0.8 g/kg body weight per day (the recommended daily allowance). A For patients on dialysis, higher levels of dietary protein intake should be considered, since malnutrition is a major problem in some dialysis patients. B
• In nonpregnant patients with diabetes and hypertension, either an ACE inhibitor or an ARB is recommended for those with modestly elevated UACR (30–299) B and is strongly recommended for those with UACR ≥300 and/or eGFR <60. A
• Periodically monitor serum creatinine and potassium when ACE inhibitors, ARBs, or diuretics are used. B
• An ACE inhibitor or an ARB is not recommended for the primary prevention of CKD in patients who have normal BP, normal UACR (<30), and normal eGFR. A
• Refer to a nephrologist if eGFR <30. A

Pharmacotherapy for Obesity/Weight Loss in T2D – Recommendations:

Nearly all FDA-approved medications for weight loss have been shown to improve glycemic control in patients with T2D and delay progression to diabetes for those at risk.

• When choosing medications for T2D, consider the medication's effect on weight. B
• Weight-loss medications are effective as adjuncts to lifestyle for selected patients with T2D and BMI ≥27. Potential benefits and risks must be considered. A
• If a patient’s response to weight-loss medication is effective (typically defined as >5% weight loss after 3 months’ use), further weight loss is likely with continued use. When early response is insufficient (typically <5% weight loss after 3 months’ use), or if there are significant safety or tolerability issues, consider discontinuation of the medication and evaluate alternative medications or treatment approaches. A

Mark’s Comments:

Despite the aggressive nature in which the newer diabetes medications have been advertised and detailed, metformin continues to be the first-line treatment based on the evidence. It is certainly time for us all to become more familiar with the SGLT2 inhibitors and GLP-1 receptor agonists given their specific indication for those patients with diabetes who have established ASCVD or are at very high risk for it. Additionally, the SGLT2 inhibitors also have an indication for those with CKD or HF.

I want to take a moment to highlight and re-emphasize the concept of “overbasalization” with insulin therapy, which may be a new term for some of you, as it was for me. Overbasalization, defined as excessively high fasting glucose despite increased basal insulin dose, may be occurring if the dose of basal insulin is more than ∼0.5 IU/kg, there is a high bedtime-morning or post-preprandial glucose differential, there is hypoglycemia (aware or unaware), or there is high blood sugar variability. To prevent overbasalization, the addition of mealtime insulin (bolus insulin) may be necessary using either rapid-acting or short-acting insulin. It should be noted there are limited studies on the threshold dose of basal insulin and this recommendation is mostly based on expert opinion (E).

The Standards abridged document also includes 3 very helpful algorithms/summaries for prescribing/intensifying non-insulin medications, for prescribing/intensifying insulin, and a wonderful table of all the medications with their indications, strengths, and limitations. I have included Figures 9.1 and 9.2 as a separate attachment for your reference. Many colleagues have found it helpful to print these and keep them close for reference during clinical care. In addition, a link to each of these is below.

In a future Take 3, we’ll take a “deeper dive” into continuing glucose monitoring and the associated technology.

References:

• ADA Standards for Medical Care in Diabetes – 2020: Abridged for Primary Care Providers. Clinical Diabetes 2021 Jan; 39(1): 14-43. Link : See particularly Medication Algorithm, Injectable Therapies Algorithm , and Summary Overview of DM Medications

• ADA Standards of Care 2021: January 01 2021; 44(S1). Link

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Mark and John

Carilion Clinic Department of Family and Community Medicine

Feel free to forward Take 3 to your colleagues. Glad to add them to the distribution list.

Email: mhgreenawald@carilionclinic.org