Diabetes

Disease State Overview

Diabetes is a chronic endocrine disorder characterized by lack of insulin production, varying degrees of insulin resistance, or both. Diabetes is categorized broadly into 2 types. Type 1 diabetes is characterized by a complete lack of insulin production by the pancreas while type 2 diabetes is characterized by both insulin resistance and inadequate insulin production.

Risk of Condition

Diabetes can lead to several microvascular and macrovascular complications.

Macrovascular complications of diabetes include coronary artery disease, peripheral arterial disease
and stroke.
Microvascular complications of diabetes include diabetic nephropathy, neuropathy, and retinopathy.

Medication

Role of Medication

Type 1 Diabetes: Insulin therapy is required due to the body’s loss or near loss of beta cell function resulting in no or minimal endogenous insulin production.

Types 2 Diabetes: Guidelines recommended metformin and lifestyle modifications as initial therapy in patients with type 2 diabetes. Non-insulin medications can be used to increase the body’s sensitivity to insulin or stimulate production of endogenous insulin. As type 2 diabetes progresses, insulin supplementation may be required to achieve adequate blood glucose control. Choice of therapy should be based on multiple factors including A1c, medication side effect profile, insurance coverage, patient preference, patient’s age, comorbid conditions, and concurrent medications.

Medications for the Management of Diabetes from the American Diabetes Association (ADA)

Drug Class: Biguanide
- Drug Names:
  - metformin
- Common Class Side Effects:
  - GI: diarrhea, nausea, vomiting, abdominal pain, bloating
  - Weight change: neutral
  - Hypoglycemia risk: No
    - Taking with food may minimize GI upset
Drug Class: Sulfonylurea
- Drug Names:
  - glipizide
  - glimepiride
  - glyburide
- Common Class Side Effects:
  - Weight change: gain
  - Hypoglycemia risk: yes (glyburide > glimepiride > glipizide)
Drug Class: Meglitinide
- Drug Names:
  - repaglinide
  - nateglinide
- Common Class Side Effects:
  - Weight change: gain
  - Hypoglycemia: yes
Drug Class: Thiazolidinedione
- Drug Names:
  - pioglitazone
- Common Class Side Effects:
  - Weight change: gain
  - Hypoglycemia risk: no
  - Other: edema, bone fractures, congestive heart failure (BBW), bladder cancer (pioglitazone only)
Drug Class: DPP-4 Inhibitor
- Drug Names:
  - sitagliptin (Januvia)
  - saxaglipitin (Onglyza)
  - linagliptin (Tradjenta)
- Common Class Side Effects:
  - Weight change: neutral
  - Hypoglycemia risk: no
  - Other: nasopharyngitis, upper respiratory tract infections, headache, pancreatitis, joint pain
Drug Class: GLP-1 Analog
- Drug Names:
  - exenatide (Byetta, Bydureon)
  - liraglutide (Victoza)*
  - dulaglutide (Trulicity)*
  - semaglutide (Ozempic*, Rybelsus)
- Common Class Side Effects:
  - GI*: nausea, vomiting, diarrhea
  - Weight change: loss
  - Hypoglycemia risk: no
  - Other: thyroid C-cell tumors (BBW), injection site reactions
  - *GI side effects are minimized by starting the patient on the right starting dose and following the appropriate titration schedule
Drug Class: SGLT2 Inhibitor
- Drug Names:
  - canagliflozin (Invokana)*
  - dapagliflozin (Farxiga)
  - empagliflozin (Jardiance)*
  - ertugliflozin (Steglatro)
- Common Class Side Effects:
  - Weight change: loss
  - Hypoglycemia risk: no
  - Other: Urinary tract infections, dizziness, hypotension, hyperkalemia
Drug Class: Alpha Glucosidase Inhibitor
- Drug Names:
  - acarbose
  - miglitol
- Common Class Side Effects:
  - GI: diarrhea, flatulence
  - Weight change: loss
  - Hypoglycemia risk: no
Drug Class: Amylin Analog
- Drug Names:
  - pramlintide
- Common Class Side Effects:
  - GI: nausea, vomiting
  - Weight change: loss
  - Hypoglycemia risk: no
Drug Class: Insulin
- Drug Names:
  - Rapid Acting:
    - aspart
    - glulisine
    - lispro
  - Intermediate Acting:
    - NPH
  - Short Acting:
    - regular
  - Long Acting:
    - degludec
    - detemir
    - glargine
- Common Class Side Effects:
  - Weight change: gain
  - Hypoglycemia risk: yes (highest risk)

* Demonstrated cardiovascular benefit in clinical trials and have a labeled indication of reducing CVD events. Consider in patients at high cardiovascular risk or in patients with established ASCVD.

Abbreviations used: DPP-4 = dipeptidyl peptidase-4, GLP-1 = glucagon-like peptide-1, SGLT2 = sodium-glucose cotransporter-2

Cardiovascular Disease Management in Diabetes

Cardiovascular disease (CVD) is the leading cause of death amongst people with diabetes making cardiovascular risk management an essential component diabetes management.

Hypertension Therapy
- Recommended Medication Options:
  - ACEi (first-line therapy), stands for angiotensin converting enzyme inhibitor
  - ARB (first-line therapy) , stands for angiotensin receptor blocker
  - Calcium channel blocker
  - Thiazide diuretic
- Rationale:
  - Hypertension is common in people with diabetes and increases risk of microvascular complications
Lipid Therapy
- Recommended Medication Options:
  - Primary Prevention
  - Moderate-intensity statin (all patients age 40 – 75 years)
  - High-intensity statin (multiple ASCVD risk factors or age 40-75 years)
  - Ezetimibe (consider adding to max tolerated statin in patients with ASCVD risk > 20%)
  - Secondary Prevention - High-intensity statin
- Rationale:
  - Statin therapy has been shown to decrease cardiovascular risk in people with diabetes with and without coronary heart disease.
Antiplatelet Therapy
- Recommended Medication Options:
  - Primary Prevention
  - Aspirin (high risk patients only)
  - Secondary Prevention
  - Aspirin
  - Clopidogrel (patient with allergy to aspirin)
  - DAPT (only used in certain patients)
- Rationale:
  - Aspirin has been shown to reduce cardiovascular morbidity and mortality in high-risk patients using for secondary prevention. For use in primary prevention, risk of bleed may outweigh potential benefit so risks should be discussed with the patient.

Adherence

Medication adherence is an essential component of treating diabetes and preventing further complications. Discuss barriers to adherence and provide appropriate solutions. You may use the DRAW tool located within the Worksheets & Forms category in this Knowledge Base.

Administration

Pharmacists play a key role in the training and education of appropriate administration and storage of insulin and other injectables. Refer to the package insert or manufacturer website of the specific product for further guidance.

Monitoring

The goal of therapy is to reduce microvascular and macrovascular complications by achieving and maintaining glycemic control while minimizing the risk of side effects. Treatment should be reassessed and modified on a regular basis (every 3-6 months) to ensure treatment appropriateness and efficacy.

Hemoglobin A1c

A1c should be monitored every 3 months if uncontrolled and every 6 months if controlled. Although target A1c should be individualized per patient, the American Diabetes Association (ADA) and the American Association of Clinical Endocrinologist provide the following recommendations:

ADA
- General Recommendations: <7
- Older Adults: <7 - 7.5
ACCE
- General Recommendations: <6.5

Blood glucose

Blood glucose should be monitored regularly in patients with diabetes and can be self-monitored in many cases. Glucose targets may be altered based on many factors including duration of diabetes, age/life expectancy, and comorbid conditions. However, general recommendations are outlined below:

ADA
- Fasting/Pre-prandial: 80-130 mg/dL
- Peak post prandial: < 180 mg/dL
ACCE
- Fasting/Pre-prandial: <110 mg/dL
- Peak post prandial: <140 mg/dL

Health Screenings

In addition to regular monitoring of A1c and blood glucose, patients with diabetes should receive the following screenings/exams:

Eye exams (at least annually)

Renal function (at least annually)

Blood pressure screenings (at every routine visit)

Foot exams (at least annually)

Dental exams

Lifestyle Education

Lifestyle modifications can provide great benefit in patients with diabetes. Discussion points may include:

Encourage weight loss in patients who are overweight or obese

Encourage a healthy diet which may include meal planning, counting carbohydrates, and/or the “MyPlate” method

Recommend 150 minutes or more of moderate-to vigorous intensity aerobic activity each week spread over at least 3 days of the week

In patients who smoke, recommend smoking cessation and provide counseling on appropriate options and resources
Strongly encourage participation in a diabetes self-management education and support (DSMES) program if available

Additional Points

Immunization Assessment:

It is important to review a patient’s immunization history and recommend vaccines that are important in patients with diabetes by the Advisory Committee on Immunization Practices (ACIP) and the Centers for Disease Control and Prevention (e.g. influenza, pneumonia, Hepatitis B).

Hypoglycemia Education:

Patients should be instructed how to treat and monitor for signs and symptoms of hypoglycemia, including: dizziness, hunger, sweating, shakiness, confusion, and lightheadedness. Hypoglycemia in patients with diabetes is generally defined as a blood glucose of < 70mg/dL.

Rule of 15 for Treating Hypoglycemia

Resources:

American Diabetes Association. Standards of Care in Diabetes – 2024. Diabetes Care 2024.
https://diabetesjournals.org/care/issue/47/Supplement_1
Blonde L, Umpierrez GE, Reddy SS, et al. American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update [published correction appears in Endocr Pract. 2023 Jan;29(1):80-81. doi: 10.1016/j.eprac.2022.12.005]. Endocr Pract. 2022;28(10):923-1049. doi:10.1016/j.eprac.2022.08.002
https://pubmed.ncbi.nlm.nih.gov/35963508/
Consensus Statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive Type 2 Diabetes Management Algorithm – 2020 Executive Summary. Endocr Pract. 2020;26(1): 107 – 139.
https://www.endocrinepractice.org/action/showPdf?pii=S1530-891X%2820%2935066-7