Diabetes Medications

Transforming Diabetes Care –

Changes and Choices

April 18, 20151

Objective

Discuss New diabetes medications and their role in

treatment

Conflict of InterestI have no conflict of Interest

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Diabetes

• 40-50% of the US Population is expected to

develop Diabetes in their lifetime.

• If type 2 diabetes were a country it would be

the 3rd largest in the world.

• 90% of the tasks of diabetes management are

done at home by the patient – we better do a

good job of education. 3

Diabetes Medications and

Insurance Companies

• Every Insurance Company has a Formulary

• Tells you what medications they will pay for.

• And they all have this statement “this list of medications may change at any moment without warning or notice”.

• Be alert for the patient who has just changed insurance companies

• They usually don’t know what the new company (or their current insurance company) will pay for. Meters, test strips, meds, pumps, type of insulin.

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The 1st Line Treatment for

Diabetes

• Lifestyle changes• Decrease weight

• Recommend to lose 7-10% of current weight, if overweight

• Increase exercise

• Recommend 150 minutes per week

• Maintain the first two.

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DPP4-I, GLP-1

TZD

SGLT2-I

Metformin, TZDCycloset, GLP-1

Metformin, GLP-1

Metformin, GLP-1, Insulin, food

Insulin,GLP-1,

Sulfonylureas,

Meglitinides

Stimulates production of Insulin

Sulfonylurea

• Glipizide, Glyburide, Glimipride

• Glucotrol, Glynase, Diabeta, Micronase, Glucotrol XL,

• $4 / Month pill

• Low blood sugar

• Nausea / vomiting

• Hypoglycemia is the biggest concern.

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Insulin Sensitizer/Decreases

effect of Glucagon - Metformin

Biguanide• Glucophage, Glucophage XR, Fortamet, Riomet

• Decreases the liver’s glucose production – from inappropriate glucagon release

• Opens the cell and allows the body to use the insulin more efficiently – increases sensitivity.

• GI upset, diarrhea, gas - 30% of people will have this, of that 30% will have to stop the pill. Formulation change?

• Check the Creatinine >1.4 in women & >1.5 in men.

• Stop 24 hours before & after dye test. The most important is after the dye. 12 hour half life.

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Insulin Sensitizer - Metformin

• Use with caution in people with liver or kidney

problems.

• Take the pill with food to help decrease Gas and

decrease irritation to stomach.

• Used in PCOS to break the insulin resistance along

with lifestyle changes. .

• $4 / month pill

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Insulin Sensitizer -Thiazolidinedione

TZD

• Actos (Pioglitazone), Avandia (Rosiglitazone)

• Works at peripheral cells to help open the cells

and allow the body to use the insulin more

efficiently

• Watch for edema, weight gain (sodium shift)

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Insulin Sensitizer TZD’s

• Also may be used in PCOS.

• Might be effective in diabetes prevention

• Big controversy with Avandia so you won’t see this used much. It is on the market.

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Insulin Stimulator

Meglitinade Insulin Secretagogue

• Prandin (Repaglinide), Starlix (Nagletinide)

• Take at the beginning of each meal

• Works for 2 hours after taken

• Low blood sugar

• The problem with these pills is you have to take them at the beginning of the meal, since it works for 2 hours. People would forget.

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Alpha Glucosidase Inhibitor

• Precose, Glyset

• These drugs work in the intestines to slow the digestion of some carbs so that after meal blood sugar peaks are not so high.

• Take at the START of each meals

• GI upset, GAS, abdominal pain very common

• Hypoglycemia must be treated with pure glucose tabs, gel or milk as food absorption is delayed.

• You have to take this with the first bite of food –patients always forgot.

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DPP-4 Inhibitors

• Blocks the DPP4 enzyme so native GLP-s is not degraded, allows GLP-1 to stimulate insulin producation

• Does not interfere with any other medications or foods. This is an enzyme

• Caution using in patients with history of pancreatitis or medulary thyroid cancer

• New study found this has not happened.

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DPP-4

• Januvia (Sitagliptin)

• Onglyza (Saxagliptin)

• Tradgenta (Linagliptin)

• Nesina (Alogliptin)

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SGLT – 2 Inhibitor

• Normally the kidney

reabsorb glucose primarily

via SGLT2, sodium-glucose

co-transporter 2,

protein located in the proximal

tubule of the nephron.

• By inhibiting SGLT2,

these medications block

reabsorption of glucose thereby

increasing urinary glucose excretion.

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Selective Sodium-Glucose

Transporter

• The patient excretes more glucose through the kidneys out the urinary tract

• Will be glucosuria

• Patient may lose 300 calories/day, may decrease BP

• Side effects

• Vaginal infections,

• UTI

• Volume depletion19

SGLT – 2 Inhibitor

• Invokana (canagliflozin)

• Farxiga (dapagliflozin)

• Jardiance (empagliflozin)

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SGLT-2 Inhibitors and Kidney

Function

• Estimated Glomerular Filtration Rate/Kidney

Disease

• GFR > 60 – Great, no problem using the pills

• GFR 45 to 60 – Use the lower dose

• GFR < 45 – Avoid the meds (although some company’s

will say “use with caution” consider a safer alternative.

• If GFR down to 30’s need a nephrologist.

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Medications

Some pills are in combination

• ActoPlus Met – Actos and Metformin

• Avandamet – Avandia & Metformin

• Avandaryl - Avandia and Amaryl

• Duetact – Actos and Glimepiride

• Glucovance – Glyburide & Metformin

• Metaglip – Glipizide & Metformin

• Prandimet – Prandin and Metformin 22

Newer Combination Pills

• Janumet – Januvia and Metformin IR and ER

• Kombiglyze – Onglyza and Metformin ER

• Jentadueto – Tradjenta and Metformin

• Kazano – Alogliptin and Metformin

• Oseni – Alogliptin and Metformin

• Invokamet – Invokana and Metformin

• Xigduo XR – Farxiga and Metformin ER

• Glyxambi – Jardiance and Tradjenta 23

Amylin Symlin

• Symlin – (Pramlintide)

• Amylin is a hormone made in the beta cells.

• Amylin deficiency can make it harder to control glucose levels after meals.

• Reduces fluctuations of blood sugar

• Used with type 1 or 2 at every meal.

• Must eat 250 calories or 30 grams of carbs

• Watch for hypoglycemia

• Problem: Cost and so many shots24

Glucose Like Peptide – 1

GLP-1

• Replaces the GLP-1 hormone that is not being made or used. Responsible for the “incretin effect” 50-70% of insulin release with a meal

• Decreases glucagon release

• Slows gastric emptying

• “Satiety” hormone, helps people feel full faster

• People feel full longer, decrease food intake

• Nausea – transient, or with high fat meal25

GLP-1 - Replaces/Enhances

GLP-1

• Byetta (Exenatide) -Twice a day (2005)

• Victoza (Liraglutide) - Once a day

• Bydureon (Exenatide XR) - Once a week

• Tanzeum (Albiglatide) - Once a week

• Trulicity (Dulaglutide) - Once a week

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Insulin

Replaces what the body

can not make enough of

or does not use properly

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Cost of Insulin

• Sometimes this is the barrier for patients

• Insulin can cost $435 or more/vial

• NPH / Regular / Reli-On Brand cost $25-35/vial

• Sometimes skipping medications is cost related –

always ask them.

• Patient Assistant Programs

• Use of Free or Reduced Drug Cards

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Medications - Insulin

• Insulin is divided into four categories

1. Long Acting – Lantus, Levemir

2. Intermediate Acting – NPH (cloudy insulin)

3. Short Acting - Regular

4. Very Short Acting – Humalog / Novolog / Apidera

• All Insulin is now made in laboratories, not from animals

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Rapid Acting

Humalog / Novolog / Apidra

• Onset 5 to 15 minutes.

• Given at the meal to “cover” the food at the

meal.

• Peak action is 1 hour.

• Duration is 2-3 hours.

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Rapid Acting

Humalog / Novolog / Apidra

• Is Used in the Insulin Pump.

• Is used in the V-GO

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Inhaled Insulin Afrezza

• A rapid acting inhaled insulin

Inhaled powder delivered using a small, discreet and easy to use inhaler – looks like a whistle.

• Administer at the start of the meal.

• Afrezza disolves instantly upon inhalation to the deep lung and delivers to blood stream – OK to use if you have a cold, allergies. Lung clearance very good.

• Peak insulin levels are achieved within 12 to 15 minutes of administration, and decline to baseline by approximately 180 minutes.

• Must be used in combination with a long acting insulin.

• Must have Baseline Spirometry before starting this medication.32

Fast Acting

Regular

• Onset 30 minutes, so should be given 30 minutes before a meal.

• Peak action is 1 – 3 hours.

• Duration is 5 to 6 hours.

• Main uses • Patient with Gastroparesis

• Patient with 24 hour tube feedings

• IV Insulin – 5 minute half life

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Intermediate Acting

NPH

• Onset 1-1 ½ hours

• Peak is 6 – 10 hours

• Duration is 12 – 16 hours

• Generally given at breakfast and bedtime

• Cloudy insulin – Be sure to mix thoroughly.

• May be used in pregnancy – generally at HS to control early morning blood sugars.

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Long Acting

Lantus (Glargine)/Levemir (Detemir)

• Onset in 1 – 1 ½ hours

• Duration is 24 hours

• Needs to be given at a consistent time

• Generally given at bedtime or morning

• Some may need twice a day shots

• May burn at the injection site

• Can Not be mixed with any other insulin

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New

Toujeo (Lantus) U300

• The large insulin molecule (lantus) is shrunk to a

smaller molecule so you have smaller surface area

which releases more consistently

• 1/3 Less volume

• 6 hours to reach peak (if there is a peak)

• 5 days to steady state

• More consistent duration of 24-36 hours – should

not need BID dosing. 36

When to give the Long Acting

Insulin

• At Bedtime

• If there is a peak, it will peak early morning.

• Many people have early morning high blood sugars.

• Judge if this is a good dose by the FBS

• At Breakfast

• If there is a peak it will peak in the evening

• May have a better weight loss with morning shot

• Check blood sugar before bed to determine if this is a good dose.

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Concentrated Insulin

• Regular U500 Insulin

• Is 5X more concentrated than insulin.

• 5 units of U500 is 25 units of U100 insulin

• Comes in 20 mL vials

• Generally given 3 times a day, with the three meals

• Try to spread the meals apart 6+ hours.

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Combination Insulin

• 70/30 – 70% NPH & 30% Regular

• 75/25 – 75% NPH & 30% Humalog

• 50/50 – 50% NPH & 50% Humalog

• Novolog Mix 70/30 – 70% NPH & 30% Novolog

Insulin with the name Novolin or Humulin is usually NPH mixed with regular

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What may be new?

• IDegLira

• Injectable medication that combines Victoza and

an Ultralong acting Basal Insulin degludec (a 42

hour insulin).

• Brand name will be Xultophy

• Fixed dose of GLP-1 and Insulin.

• Cost expected to be high

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What may be new?

• Long Acting DPP4

• All DPP4’s last 24 hours, but they are working on

a once week version.

• Omarigliptin 25 mg, lowers Alc 0.71 mg in a 12

week study.

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FDA approved Liraglutide for Weight

Loss

• Liraglutide (Victoza) now called Saxenda has been

approved as a treatment for chronic weight management

along with reduced calorie diet and physical activity

• Saxenda is a GLP-1 and can not be used with any other

GLP-1.

• Victoza doses is 0.6, 1.2 or 1.8 mg and Saxenda is 3 mg

• Concern will be nausea

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Step wise approach to

Type 2 Treatment1. Lifestyle changes

2. Inititate Metformin (lower Alc by 1-2%)

3. If Alc > 7% after 3 months... (not in any order)

1. Add sulfonylurea (lower Alc by 1-2%)

2. TZD (lower Alc by 0.5 – 1.4%)

3. DPP4-I (lower Alc by 0.7-1.2%)

4. GLP-1 (lower Alc by 0.5 – 1%)

5. SGLT-2-I (lower Alc by 0.7-1.5%)

6. Basal insulin (lower Alc by 1.5%)

7. Mealtime (bolus) insulin (1 or more meals)43

Step wise approach to

Type 2 TreatmentDecision on what medications to use

Based on ADA/EASD Recommendations 2012

Individualized decisions based on 7 factors

Patient attitude and expected treatment effort

Hypoglycemia and other risks

Disease duration

Life expectancy

Comorbidities

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continued

Established vascular complications

Resources, support system

Every medication regimen should be specifically designed for

that person

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Questions

• Rebecca Newberry APRN MS CDE

Diabetes Education Center of the Midlands

Omaha, Nebraska 68124

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