TREATMENT OF MELLITUS

DIABETES is a condition that affects how the body makes energy from food. Food is broken down into () in the body and released into the blood. When the blood sugar level rises after a meal, responds to let the sugar into the cells to be used as energy. In diabetes, the body either does not make enough insulin or it stops responding to insulin as well as it should. This results in sugar staying in the blood and leads to serious health problems over time.

DIAGNOSIS OF DIABETES1 • A1C Test: Lab test measuring average blood sugar over past two to three months • Fasting Blood Sugar Test: Lab test measuring blood sugar after eight hours of no food or drink • Oral Glucose Tolerance Test (OGTT): Measures blood sugar before and two hours after drinking a specific sugary liquid • Random Blood Sugar Test: Measures blood sugar at a moment in time, without any kind of preparation (like fasting)

FASTING BLOOD ORAL GLUCOSE TOLERANCE RANDOM BLOOD RESULT A1C TEST SUGAR TEST TEST SUGAR TEST Diabetes ≥ 6.5% ≥126 mg/dL ≥ 200 mg/dL ≥ 200 mg/dL 5.7 – 6.4% 100 – 125 mg/dL 140 – 199 mg/dL N/A Normal < 5.7% ≤99 mg/dL < 140 mg/dL N/A

NON-DRUG TREATMENTS2

THERAPY COST WHAT TO EXPECT Diet (Mediterranean diet) and exercise (30 minutes a day, five days a week of moderate- Weight loss $-$$ intensity exercise); 7% weight loss decreases risk of diabetes3

Psychological intervention $$-$$$ Psychotherapy may reduce diabetic distress and improve glycemic control4,5

nationalcooperativerx.com

PRESCRIPTION TREATMENTS

THERAPY SUB-CATEGORY NOTES FORMULARY TIER

Insulins – increase uptake of sugar into cells; in general, vials are less expensive than pens for those who pay a percentage of prescription costs; exceptions are noted below (NOVOLOG©, Used just before meals (“bolus”) or in insulin FIASP©) Rapid-acting pumps; effect lasts about three to five hours Tier 2 ($$$$) Vials and Pens Used 30 minutes before meals; less convenient Insulin Regular (NOVOLIN R©) Short-acting but a lower-cost option Tier 2 ($$) Vials and Pens Insulin Regular (HUMULIN RU- Concentrated version of insulin regular; used 30 500) Short-acting minutes before meals Tier 2 ($$) Vials and Pens Doesn’t last as long as long-acting ; peak Insulin NPH (NOVOLIN N©) Intermediate-acting effect in four to 10 hours Tier 2 ($$) Vials and Pens (BASAGLAR©) Lasts about 24 hours with steady action Long-acting Pens throughout the day Tier 2 ($$) Doesn’t always last 24 hours (may need twice (LEVEMIR©) Long-acting daily dosing); vials and pens are same price per Tier 2 ($$$) Vials and Pens mL (TRESIBA©) Longest-acting (once daily dosing); vials and Ultra long-acting Vials, U100 Pens, U200 Pens pens same price per unit of insulin Tier 2 ($$$) Insulin Aspart Protamine and Insulin Aspart (NOVOLOG MIX Given 15 minutes before a meal, two to three Tier 2 ($$$) Combination 70/30©) times per day; can last up to 24 hours Vials and Pens Insulin NPH and Insulin Regular Given 30 minutes before a meal, two to three (NOVOLIN 70/30©) Combination times per day; can last up to 24 hours Tier 2 ($$$) Vials and Pens

Amylin Analogs – slow stomach emptying, reduce appetite, lessens blood sugar spikes from meals

Taken with meals; lowers appetite, slows stomach emptying, lessens mealtime sugar spikes; must take fast-acting oral medicines one (SYMLINPEN©) Tier 2 ($$$$) hour before or two hours after Symlin; not widely used because of side effects in the GI tract and low blood when used with insulin GLP-1 Receptor Agonists – slow digestion and lower blood sugar; low risk of ; common side effects are and ; rare occurrence of Shown to lower risk of cardiovascular (TRULICITY©) Weekly injections events in people with and without Tier 2 ($$$) history of previous event Shown to lower risk of cardiovascular (VICTOZA©) Daily injections events in those with heart disease; Tier 2 ($$$$) may have risk of gallbladder disease

TREATMENT OF DIABETES MELLITUS

Shown to lower risk of cardiovascular (OZEMPIC©) Daily injections events in those with heart disease; Tier 2 ($$$) may have risk of retinopathy Only oral GLP-1 product; must be Semaglutide (Rybelsus®) Daily Tier 2 ($$$) taken on empty stomach

Sulfonylureas – helps body secrete more insulin; tends to lose effectiveness after a while

Causes more hypoglycemia and weight gain than second generation First generation Tier 1 ($$) ; should not be used in the elderly or those with poor function Once daily dosing; very little benefit Second generation Tier 1 ($) above 4mg daily Twice daily dosing; very little benefit Second generation Tier 1 ($) above 10mg daily Causes more hypoglycemia and weight Glyburide Once or twice daily with food Tier 1 ($) gain than glipizide or glimepiride Cause more hypoglycemia and weight First generation gain than second generation Tier 1 ($$) sulfonylureas Cause more hypoglycemia and weight gain than second generation First generation Tier 1 ($$) sulfonylureas; increased risk of death from cardiovascular events

Biguanides – lowers the body’s sugar production and improves the body’s use of insulin

First-line treatment for most people with diabetes type II; does not cause weight gain; can cause diarrhea, but usually goes away within a couple Tier 1 ($) weeks; start at low dose and slowly increase to minimize this; can cause vitamin B12 deficiency, so need to monitor Analogs – works like sulfonylureas, faster-acting; can cause hypoglycemia and weight gain; less hypoglycemia than sulfonylureas and more dosing flexibility

Nateglinide Very little data on cardiovascular risk, but seems to be neutral Tier 1 ($$)

Repaglinide No data on cardiovascular benefit or risk Tier 1 ($$)

Alpha-Glucosidase Inhibitors – prevent digestion of sugars; may cause gas and diarrhea; low risk of hypoglycemia; do not cause weight gain

nationalcooperativerx.com

Acarbose Neutral effect on cardiovascular risk Tier 1 ($)

Miglitol No data on cardiovascular risk Tier 1 ($$)

Dipeptidyl Peptidase-4 (DPP-4) Inhibitors – help body secrete more insulin, slow digestion of food

Sitagliptin (JANUVIA®) Seems to have neutral cardiovascular risk Tier 2 ($$$)

Thiazolidinediones - improve body’s use of insulin; cause weight gain and risk of fracture; low risk of hypoglycemia

May reduce risk of heart attack or stroke; may improve ; may (Actos®) Tier 1 ($) increase risk of and bladder cancer

Rosiglitazone (Avandia®) May increase LDL (bad cholesterol) and risk of heart failure Tier 3 ($$)

Sodium Glucose Co-Transporter 2 (SGLT2) Inhibitors – prevent body from taking sugar into blood; may help with weight loss; may cause urinary tract and yeast infections, low , increased LDL (bad cholesterol), increased potassium, increased risk of fractures and amputations

Dapagliflozin (FARXIGA®) May increase risk of bladder cancer and kidney injury Tier 2 ($$$)

Empagliflozin (JARDIANCE®) Lowers risk of cardiovascular events Tier 2 ($$$)

Combinations - see notes about effectiveness and safety above for each drug Insulin Degludec and Liraglutide Combination of Tresiba® and Victoza®; more cost-effective than taking both Tier 2 ($$$) (XULTOPHY©) drugs separately Insulin Glargine and Combination of Lantus/Basaglar® and Adlyxin®; more cost-effective than Tier 2 ($$$) (SOLIQUA©) taking both drugs separately and Metformin Combination of Januvia® and metformin; combination tablet cost-neutral to Tier 2 ($$$) (JANUMET©) the separate products and Metformin Combination of Farxiga® and metformin; combination tablet cost-neutral to Tier 2 ($$$) (XIGDUO©) the separate products and Metformin Combination of Jardiance® and metformin; combination tablet cost-neutral to Tier 2 ($$$) (SYNJARDY©) the separate products Empagliflozin and Combination of Jardiance® and Tradjenta®; combination tablet cost-neutral to Tier 2 ($$$) (GLYXAMBI©) the separate products

Glipizide and Metformin Combination tablet more expensive than separate products Tier 1 ($$)

Glyburide and Metformin Combination tablet more cost-effective than taking both drugs separately Tier 1 ($)

Pioglitazone and Glimepiride Combination tablet more expensive than taking both drugs separately Tier 1 ($$$)

Pioglitazone and Metformin Combination tablet more expensive than taking both drugs separately Tier 1 ($$)

TREATMENT OF DIABETES MELLITUS

1. American Diabetes Association. Diagnosis. https://www.diabetes.org/a1c/diagnosis. Accessed March 10, 2020. 2. Wexler DJ. Initial management of blood glucose in adults with mellitus. In: UpToDate, Mulder JE, UpToDate, Waltham, MA, 2019. 3. Knowler WC, Barret-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346(6):393-403. 4. Ismail K, Winkley K, Rabe-Hesketh S. Systematic review and meta-analysis of randomised controlled trials of psychological interventions to improve glycaemic control in patients with type 2 diabetes. Lancet. 2004;363(9421):1589-97. 5. Safren SA, Gonzalez JS, Wexler DJ, et al. A randomized controlled trial of cognitive behavioral therapy for adherence and depression (CBT-AD) in patients with uncontrolled type 2 diabetes. Diabetes Care. 2014;37(3):625-33. 6. Dispel Concerns About CV Safety With Sulfonylureas. Pharmacist’s Letter, December 2019. 7. Diabetes and Cardiovascular Impact. Pharmacist’s Letter/Prescriber’s Letter. January 2019

nationalcooperativerx.com