Post on 27-Jan-2022
DIABETES TYPE II
PHARMACOLOGIC THERAPY 2019
Meena Qazizada, Pharm.D, BCMAS Yasuno Sato, Pharm.D.
October 15, 2019
GUIDELINES
American Diabetes Association® (ADA) 2019
The American Association of Clinical Endocrinologists (AACE)
TABLE OF CONTENTS 1. Principles of Treatment of Type 2 Diabetes
2. Glycemic Control Algorithm
3. Main Oral and Injectable Pharmacotherapy
4. Cardiovascular Outcomes Trials
5. Alliance Formulary
6. Link to Alliance Formulary Document and Prior Authorization Criteria
PRINCIPLES
1. Lifestyle modification underlies all therapy (e.g., weight control, physical activity, sleep etc.)
2. Avoid hypoglycemia
3. Avoid weight gain
4. Individualize all glycemic targets (A1C, FPG, PPG)
5. Optimal A1C is ≤6.5%, or as close to normal as safe and achievable
6. Therapy choices are affected by initial A1C, duration of diabetes and obesity
7. Choice of therapy reflects cardiac, cerebrovascular and renal status
8. Comorbidities must be managed for comprehensive care
9. Get to goal as soon as possible
10. Choice of therapy includes ease of use and cost
11. A1C ≤6.5% for those on any insulin regimen as long as CGM is being used
AACE 2019 EXECUTIVE SUMMARY
SUMMARY OF GLYCEMIC RECOMMENDATIONS FOR
MANY NON-PREGNANT ADULTS WITH DIABETES
Tests Recommendations
A1C <7.0% (53 mmol/mol)*
Pre-prandial capillary plasma glucose 80–130 mg/dL* (4.4–7.2 mmol/L)
Peak postprandial capillary plasma glucose† <180 mg/dL* (10.0 mmol/L)
*More or less stringent glycemic goals may be appropriate for individual patients. Goals should be individualized based on
duration of diabetes, age/life expectancy, comorbid conditions, known CVD or advanced microvascular complications,
hypoglycemia unawareness, and individual patient considerations.
† Postprandial glucose may be targeted if A1C goals are not met despite reaching preprandial glucose goals.
Postprandial glucose measurements should be made 1–2 h after the beginning of the meal, generally peak levels in
patients with diabetes.
ADA Diabetes Care 2019
Alliance Care Management (CM) works with individuals to improve their health and quality of life.
These services are voluntary and available to all eligible members. Alliance Services include:
Healthy Weight for Life
Wellness that Works Support Program (formerly known as Weight Watchers)
Live Better with Diabetes
Tobacco Cessation Program
Complex Case Management
ALLIANCE CARE MANAGEMENT SERVICES
Alliance Care Management Services Referrals and Contact: (800) 700-3874 ext. 5512
or www.ccah-alliance.org/case_management.html.
How would you treat the following:
• Newly diagnosed patients?
• A1C >7.5%? A1C >9%? Symptoms of hyperglycemia?
• Patients with history of established ASCVD?
• CKD or HF patients?
• Patients still not at goal despite dual or triple therapy?
• Older patients?
What medications are on the Alliance formulary?
PHARMACOLOGIC THERAPY RECOMMENDATIONS 1. Metformin is the preferred initial agent.
2. The early introduction of insulin should be considered if evidence of ongoing catabolism, if symptoms of hyperglycemia are present, or when A1C levels or blood glucose levels are very high.
3. Consider initiating dual therapy in patients who have A1C ≥1.5% above target.
4. Patient-centered approach should be used to guide the choice of pharmacologic agents.
5. If established atherosclerotic cardiovascular disease (ASCVD), sodium–glucose cotransporter 2 (SGLT-2) inhibitors, or glucagon-like peptide 1 (GLP-1) receptor agonists with demonstrated cardiovascular disease benefit are recommended.
ADA Diabetes Care 2019
PHARMACOLOGIC THERAPY RECOMMENDATIONS 6. Among patients with ASCVD at high risk of heart failure or in whom heart failure
coexists, SGLT-2 inhibitors are preferred.
7. If chronic kidney disease, consider use of a SGLT-2 inhibitor or GLP-1 agonist shown to reduce risk of chronic kidney disease progression, cardiovascular events, or both.
8. If an injectable medication is needed, GLP-1 agonists are preferred to insulin.
9. Intensification of treatment should not be delayed.
10. Reevaluate at regular intervals (every 3–6 months) and adjust as needed to incorporate new patient factors.
ADA Diabetes Care 2019
Glucose-lowering medication in type 2 diabetes: overall approach.
American Diabetes Association Dia Care 2019;42:S90-S102 ©2019 by American Diabetes Association
BIGUANIDE Drug Metformin, Metformin ER (Glucophage XR) 500mg
MOA ↓ Hepatic gluconeogenesis production ↓ Intestinal absorption of glucose ↑ Insulin sensitivity ↓ Fasting & postprandial hyperglycemia
ADR Bloating, abdominal discomfort, diarrhea
Monitor Renal function (eGFR ≥30 mL/min or ≥45 mL/min for new start) Hepatic function Vitamin B12 deficiency
Which medications are preferred for patients with established ASCVD in addition to metformin?
A. GLP-1 agonists
B. DPP4 inhibitors
C. SGLT2 inhibitors
D. A & B
E. A & C
ASCVD: coronary heart disease, cerebrovascular disease, or peripheral arterial disease (PAD) presumed to be of atherosclerotic origin
POLL QUESTION #1
Glucose-lowering medication in type 2 diabetes: overall approach.
American Diabetes Association Dia Care 2019;42:S90-S102 ©2019 by American Diabetes Association
SGLT2 INHIBITOR Drug Class Steglatro, Invokana, Farxiga, Jardiance
MOA Inhibits sodium-glucose cotransporter 2 (SGLT2) ↓ Glucose reabsorption ↑ Urinary glucose excretion
ADR Genitourinary infections, UTI, volume depletion/hypotension
Caution Renal function (eGFR ≥45 mL/min, ≥60 mL/min for Steglatro) DKA
Benefits ASCVD: Jardiance, Invokana CHF: Jardiance, Invokana, Farxiga CKD: Jardiance, Invokana, Farxiga
CARDIOVASCULAR OUTCOMES TRIALS (CVOT): SGLT2 INHIBITORS
Empagliflozin (Jardiance): ↓ Composite three-point major cardiovascular event (MACE) outcome and mortality.
Canagliflozin (Invokana): ↓ MACE in a group of subjects with/ or at high risk for ASCVD.
Dapagliflozin (Farxiga): ↓ Rate of hospitalization for heart failure.
Empagliflozin, canagliflozin, and dapagliflozin:
↓ Hospitalization for heart failure.
Beneficial effects on composite of CKD progression.
MACE: Major adverse cardiovascular events
According to ADA guidelines, which of the following medications are preferred 2nd line agents after metformin for patients with type 2 diabetes and heart failure or CKD?
A. DPP4 inhibitors (alogliptin, Januvia)
B. SGLT2 inhibitors (Jardiance, Invokana, Farxiga)
C. Sulfonylureas (glipizide, glyburide)
D. All of the above
POLL QUESTION #2
GLP-1 RECEPTOR AGONIST Drugs Trulicity*, Byetta, Bydureon, Victoza, Ozempic, Adlyxin
MOA Activates glucagon-like-peptide-1 (GLP-1) receptor ↑ Insulin secretion; ↓ Glucagon secretion; Delays gastric emptying (incretin mimetic)
ADR Nausea/vomiting/diarrhea, abdominal pain, dyspepsia, ↓ appetite
Caution BBW: Medullary thyroid carcinoma Multiple endocrine neoplasia syndrome type 2 Pancreatitis Gastroparesis or severe GERD CLcr ≥30 mL/min for exenatide
Benefits ASCVD: Victoza, Trulicity, Ozempic
*Requires prior authorization
CARDIOVASCULAR OUTCOMES TRIALS (CVOT): GLP-1 AGONISTS
Liraglutide (Victoza): ↓ MACE and CV-related mortality.
Dulaglutide (Trulicity): ↓ Risk of primary composite outcome of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes.
Semaglutide (Ozempic): Favorable effects on MACE endpoint in high-risk subjects.
Liraglutide, dulaglutide, and semaglutide:
↓ Progression of albuminuria.
Neutral effect for hospitalization for HF. MACE: Major adverse cardiovascular events
According to ADA guidelines, which of the following medications are preferred 2nd line agents after metformin for patients with type 2 diabetes and established ASCVD?
A. GLP-1 agonists (Victoza, Trulicity, Ozempic)
B. SGLT2 inhibitors (Jardiance, Invokana)
C. DPP 4 inhibitors (alogliptin, Januvia)
D. Both A & B
E. All of the above
ASCVD: coronary heart disease, cerebrovascular disease, or peripheral arterial disease (PAD) presumed to be of atherosclerotic origin
POLL QUESTION #3
Glucose-lowering medication in type 2 diabetes: overall approach.
American Diabetes Association Dia Care 2019;42:S90-S102 ©2019 by American Diabetes Association
DPP4 INHIBITOR Drug Class Alogliptin, Tradjenta, Januvia, Onglyza
MOA Inhibits dipeptidyl peptidase-4 ↓ Incretin metabolism ↑ Insulin synthesis/release ↓ Glucagon levels
ADR Nausea/diarrhea, URI, headache, joint pain
Caution Renal impairment- dose adjustment (except Tradjenta) Pancreatitis Heart failure (Onglyza, alogliptin)
Due to overlapping mechanism of action, guidelines recommend against the use of which two classes in combination:
A. DPP-4 Inhibitor + GLP-1 Agonist (alogliptin + Trulicity)
B. GLP-1 Agonist + SGLT 2 Inhibitor (Trulicity + Steglatro)
C. SGLT 2 Inhibitor + DPP-4 Inhibitor (Steglatro + alogliptin)
POLL QUESTION #4
Glucose-lowering medication in type 2 diabetes: overall approach.
American Diabetes Association Dia Care 2019;42:S90-S102 ©2019 by American Diabetes Association
THIAZOLIDINEDIONES (TZD) Drug Class Pioglitazone, Avandia
MOA ↑ Insulin sensitivity in adipose tissue, skeletal muscle, and the liver
ADR Weight gain, URI, edema
Caution BBW: Congestive heart failure ↑ Bone fracture risk in postmenopausal females and elderly males Renal impairment: potential for fluid retention
ALPHA-GLUCOSIDASE INHIBITORS Drug Class Acarbose, Miglitol
MOA Inhibits pancreatic alpha-amylase and intestinal alpha-glucoside hydrolase Delays glucose absorption
ADR Nausea, abdominal pain, bloating, flatulence, diarrhea
Caution GI conditions: malabsorption, IBD, intestinal obstruction Kidney function
SULFONYLUREAS Drug Class Glimepiride, Glipizide, Glyburide
MOA ↑ Pancreatic islet beta cell insulin release ↑ Insulin sensitivity at peripheral target sites
ADR Weight gain, nausea, vomiting, diarrhea
Caution ↑ Hypoglycemia Renal impairment: avoid glyburide
According to ADA guidelines, which agents are recommended to minimize hypoglycemia for patients without established ASCVD or CKD?
A. SGLT2 inhibitors (Steglatro)
B. DPP 4 inhibitors (alogliptin)
C. GLP1 agonists (Trulicity)
D. TZDs (pioglitazone)
E. All of the above
POLL QUESTION #5
Intensifying to injectable therapies.
American Diabetes Association Dia Care 2019;42:S90-S102 ©2019 by American Diabetes Association
PRANDIAL BASAL
RAPID-ACTING SHORT-ACTING INTERMEDIATE-ACTING
LONG-ACTING
Admelog Vials & Solostar pens Humalog Novolog Fiasp
Regular insulin: Humulin R vials Novolin R vials
NPH: Humulin N vials Novolin N vials
Basaglar Kwikpen Lantus Levemir Toujeo Tresiba
INSULIN
PREMIXED INSULIN VIALS
Novolin 70/30 Humulin 70/30 Humalog Mix 75/25 Humalog Mix 50/50 Novolog Mix 70/30
*Red: requires prior authorization
Prandial Insulin Max units/ inj Basal Insulin Max units/ inj
Admelog Solostar 80 units Basaglar Kwikpen 80 units
Humalog Kwikpen U-100, U-200
60 units Lantus Solostar 80 units
Humalog Jr Kwikpen
30 units (0.5 unit increments)
Levemir FlexTouch 80 units
Novolog 60 units Toujeo Solostar 80 units
Fiasp FlexTouch 80 units Toujeo Max Solostar 160 units (2 unit increments)
Tresiba FlexTouch 80 units
Tresiba FlexTouch U-200
160 units (2 unit increments)
INSULIN PENS
OLDER ADULTS
Avoid hypoglycemia and overtreatment.
Consider less stringent goal if multiple coexisting chronic illnesses, cognitive impairment, or functional dependence.
Avoid hyperglycemia leading to symptoms or risk of acute hyperglycemia complications.
Deintensification of complex regimens is recommended to reduce the risk of hypoglycemia, if it can be achieved within the individualized A1C target.
Alliance Preferred Antidiabetic Medications Summary
• Biguanide
Metformin (Glucophage)
Metformin ER (Glucophage XR)
• SU
Glipizide
Glimepiride
Glyburide
• AGi
Acarbose
• TZD
Pioglitazone
• GLP-1 Agonist
Trulicity*
• SGLT-2 Inhibitor
Steglatro
• DPP-4 Inhibitor
Alogliptin
• Prandial Insulin
Admelog Pen and Vial
• Basal Insulin
Basaglar Pen and Vial
* Requires Prior Authorization
The Alliance provider webpage has valuable resources:
Pharmacy Formulary
Quick Reference Guides: Diabetes
Prior Authorization Form
Prior Authorization Criteria
http://www.ccah-alliance.org/pharmacy.html
ALLIANCE FORMULARY DOCUMENT AND PRIOR AUTHORIZATION CRITERIA/SUBMISSION
REFERENCES
American Association of Clinical Endocrinologists © 2019. Endocr Pract.2018;24:90-120.
American Diabetes Association. Diabetes Care 2019 Jan; 42(Supplement 1): S1-S183.
Clinical Pharmacology.
QUESTIONS?
Meena Qazizada, Pharm.D, BCMAS: mqazizada@ccah-alliance.org
Yasuno Sato, Pharm.D: ysato@ccah-alliance.org
Alliance Pharmacy Department: (831) 430-5507
Alliance Care Management: (800) 700-3874 ext. 5512
Alliance Provider Services: (800) 700-3874 ext. 5504