Diabetes – New Guidelines and Treatments

Anna Gibson, Pharm D.Lead Pharmacist, Deaconess Specialty Clinics

September, 2015

I have no actual or potential conflicts of interest to disclose.

Disclosures

Management of Hyperglycemia in Type 2 Diabetes, 2015: A Patient-Centered Approach

Update to a Position Statement of the American Diabetes Association and the European Association for the Study of Diabetes

Diabetes Care 2015;38:140–149 | DOI: 10.2337/dc14-2441

ADA position statement

Individualize goals based on:◦ Risks of hypoglycemia◦ Disease duration◦ Life Expectancy◦ Important Comorbidities◦ Vascular complications◦ Patient attitude and support system

Treatment Goals

Diabetes agents – site of action

http://diabetesmanager.pbworks.com/w/page/17680289/Oral%20Pharmacological%20Agents%20for%20Type%202%20Diabetes. Accessed 10/14/2014 1624.

Potent insulin regulating hormones◦ Released in response to glucose or fat ingestion◦ Potentiate insulin secretion◦ Additive effects

Glucose-dependent insulinotropic Polypeptide (GIP)

Glucagon-like peptide (GLP-1) Both metabolized rapidly by DPP-4 In Type 2 diabetes, GLP secretion is

decreased and GIP-induced stimulation of postprandial insulin secretion is diminished.

Incretins

GLP-1 agonists

http://diabetesmanager.pbworks.com/w/page/17680289/Oral%20Pharmacological%20Agents%20for%20Type%202%20Diabetes. Accessed 10/14/2014 1624.

Exenatide (Byetta®, Bydureon®)◦ Byetta: 5-10 mcg sq BID before meals◦ Bydureon: 2 mg sq once weekly

Liraglutide ◦ Victoza: 0.6 – 1.8 mg SQ daily◦ Saxenda (weight loss only): Start at 0.6 mg daily,

increase weekly to 3 mg daily Albiglutide (Tanzeum®)

◦ Once weekly SQ injection – 30-50 mg◦ Powder for injection – have to mix with provided diluent

and wait 15 or 30 minutes before administration. Dulaglutide (Trulicity®)

◦ Once weekly SQ injection – 0.75-1.5 mg

GLP-1agonists

a. Promote the release of endogenous incretins

b. Inhibit the breakdown of endogenous incretins

c. Act synergistically with exogenous GLP-1 agonists

d. Promote glucose excretion in the kidneys

What is the Mechanism of action of a DPP-4 inhibitor?

a. Promote the release of endogenous incretins

b. Inhibit the breakdown of endogenous incretins

c. Act synergistically with exogenous GLP-1 agonists

d. Promote glucose excretion in the kidneys

What is the Mechanism of action of a DPP-4 inhibitor?

DPP-4 inhibitors

http://diabetesmanager.pbworks.com/w/page/17680289/Oral%20Pharmacological%20Agents%20for%20Type%202%20Diabetes. Accessed 10/14/2014 1624.

Sitagliptin (Januvia®)◦ 100 mg daily

Saxagliptin (Onglyza®)◦ 2.5-5 mg daily

Alogliptin (Nesina®)◦ 25 mg daily

Linagliptin (Tradjenta®)◦ 5 mg daily

DPP-4 inhibitors

SGLT-2 inhibitors

http://diabetesmanager.pbworks.com/w/page/17680289/Oral%20Pharmacological%20Agents%20for%20Type%202%20Diabetes. Accessed 10/14/2014 1624.

Monotherapy or add-on. Efficacy comparable to sulfonylurea Weight loss Not recommended in patients with history

of bladder cancer Increase glucose excretion in urine –

increased risk for UTI/mycotic infections in genital area

Diuretic effect

SGLT-2 inhibitor

Dapagliflozin (Farxiga®)◦ 5-10 mg once daily◦ Not recommended in creatinine clearance less than 60

ml/min Canagliflozin (Invokana®)

◦ 100-300 mg once daily◦ Dose adjustment required for creatinine clearance less

than 60 ml/min, do not use in less than 45 ml/min. Empagliflozin (Jardiance®)

◦ 10-25 mg once daily◦ Do not use in creatinine clearance less than 45 ml/min

SGLT-2 inhibitor

a. 48 year old woman, newly diagnosed type 2 diabetic with a history of chronic UTI

b. 66 year old man, 10 year history of diabetes, Creatinine clearance 40 ml/min

c. 52 year old woman, 5 year history of diabetes, previously well controlled on metformin, now with Hgb A1C 8.4.

d. 67 year old man with uncontrolled diabetes who currently takes furosemide to control hypertension

Which patient is the best candidate for an SGLT-2 inhibitor?

a. 48 year old woman, newly diagnosed type 2 diabetic with a history of chronic UTI

b. 66 year old man, 10 year history of diabetes, Creatinine clearance 40 ml/min

c. 52 year old woman, 5 year history of diabetes, previously well controlled on metformin, now with Hgb A1C 8.4.

d. 67 year old man with uncontrolled diabetes who currently takes furosemide to control hypertension

Which patient is the best candidate for an SGLT-2 inhibitor?

Insulin Glargine◦ Patent on U100 (Lantus®) expired in 2/2015

Biosimilar approved in Europe Submitted to FDA as new drug in US (Basaglar®)

Tentative approval in 8/14

◦ Insulin Glargine U-300 Toujeo® Longer half-life and flatter activity curve

Less hypoglycemia

Insulin lispro ◦ 200 unit/ml◦ Humalog U-200 Kwikpen®◦ Not for IV use or for use in insulin pumps◦ Can not be mixed with any other insulins

New insulins in the pipeline

Insulin Peglispro◦ Basal insulin

Insulin Degludec (Tresiba®)◦ Ultra long acting◦ 100 unit/ml, 200 unit/ml – pens only◦ 42 hour half life may allow some patients to inject

only 2-3 times per week.

New insulins in the pipeline

Inhaled insulin◦ Afrezza®◦ 4 units per inhalation◦ Contraindicated in patients with chronic lung disease◦ Administer at the beginning of each meal◦ Round up to nearest 4 units◦ Cough, throat pain or irritation◦ Teach on proper inhalation technique

Oral insulin (Oral-Lyn®)◦ Phase 3 trials◦ Insulin spray◦ Absorbed through oral mucosa◦ Onset 5 minutes, peak 30 minutes, duration 2 hours◦ Approved in other countries, In US on Treatment IND only.

New insulins in the pipeline

Implementation of drug therapy

3 months

3 months

Add from any class with differing mechanism of action

May reach goal faster if initiate double therapy at onset◦ Consider especially if Hgb A1C > 9

DPP-4 and GLP-1 have similar mechanisms SGLT-2’s have not been tested with GLP-1’s

Implementation of drug therapy

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