Anna Gibson, Pharm D. Lead Pharmacist, Deaconess Specialty Clinics September, 2015 I have no actual or potential conflicts of interest to disclose. 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/dc142441 Individualize goals based on: ◦ ◦ ◦ ◦ ◦ ◦ Risks of hypoglycemia Disease duration Life Expectancy Important Comorbidities Vascular complications Patient attitude and support system http://diabetesmanager.pbworks.com/w/page/17680289/Oral%20Pharmacological%20Agents%20for%20Type%2 02%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. http://diabetesmanager.pbworks.com/w/page/17680289/Oral%20Pharmacological%20Agents%20for%20Type%2 02%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 a. b. c. d. Promote the release of endogenous incretins Inhibit the breakdown of endogenous incretins Act synergistically with exogenous GLP-1 agonists Promote glucose excretion in the kidneys a. b. c. d. Promote the release of endogenous incretins Inhibit the breakdown of endogenous incretins Act synergistically with exogenous GLP-1 agonists Promote glucose excretion in the kidneys http://diabetesmanager.pbworks.com/w/page/17680289/Oral%20Pharmacological%20Agents%20for%20Type%2 02%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 http://diabetesmanager.pbworks.com/w/page/17680289/Oral%20Pharmacological%20Agents%20for%20Type%2 02%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 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 a. b. c. d. 48 year old woman, newly diagnosed type 2 diabetic with a history of chronic UTI 66 year old man, 10 year history of diabetes, Creatinine clearance 40 ml/min 52 year old woman, 5 year history of diabetes, previously well controlled on metformin, now with Hgb A1C 8.4. 67 year old man with uncontrolled diabetes who currently takes furosemide to control hypertension a. b. c. d. 48 year old woman, newly diagnosed type 2 diabetic with a history of chronic UTI 66 year old man, 10 year history of diabetes, Creatinine clearance 40 ml/min 52 year old woman, 5 year history of diabetes, previously well controlled on metformin, now with Hgb A1C 8.4. 67 year old man with uncontrolled diabetes who currently takes furosemide to control hypertension 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 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. 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 ◦ ◦ ◦ ◦ ◦ 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. Oral insulin (Oral-Lyn®) 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 Basal Insulin Peglispro Studies Demonstrate Superiority to Insulin Glargine Across Multiple Measures in People with Type 1 Diabetes. http://www.prnewswire.com/newsreleases/basal-insulin-peglispro-studies-demonstrate-superiority-to-insulin-glargine-across-multiple-measures-in-people-with-type-1-diabetes-300095202.html. Accessed 8/13/15 0904. Buffery, MA, ABD. Specialty Drugs Top the Trends in the 2014 Pipeline. American Health & Drug Benefits. April 17, 2014. http://www.ahdbonline.com/issues/2014/march2014-volume-7-special-feature-fifth-annual-payers-guide-to-new-fda-approvals/1704-specialty-drugs-top-the-trends-in-the-2014-pipeline. Accessed 8/12/2015 1111. Busco, M. FDA Approves Weekly Injectable Diabetes Drug: Albiglutide. http://www.medscape.com/viewarticle/823645. Accessed 10/15/2014 1459. Comer, B. What’s in the pipeline for 2014?. Drug Topics. http://drugtopics.modernmedicine.com/print/379145. Accessed 9/24/2014. Evans, J and Rushakoff, R. Oral Agents, Incretins, and other “Non-Insulin” Pharmacologic Interventions for Diabetes. http://diabetesmanager.pbworks.com/w/page/17680289/Oral%20Pharmacological%20Agents%20for%20Type%202%20Diabetes. Accessed 10/14/2014 1624. Fennel, D. Oral Insulin Conditionally Approved by FDA. http://www.diabetesselfmanagement.com/Blog/Diane-Fennell/oral-insulin-conditionally-approved-by-fda/. Accessed 10/15/2014 1633. Fiore, C. Sanofi submits U300 to FDA. http://www.medpagetoday.com/Endocrinology/Diabetes/46690. Accessed 10/3/2014 1415. Fennell, D. Oral Insuline Conditionally Approved by FDA. http://www.diabetesselfmanagement.com/blog/oral-insulin-conditionally-approved-by-fda/. Accessed 9/8/2015 1904. Foster, M. Basal Insulin Peglispro vs. Insulin Glargine in Type 1 Diabetes. http://www.endocrinologyadvisor.com/ada-75th-scientific-sessions-2015/insulin-peglisproglargine-type-1-diabetes/article/419161/. Accessed 9/8/2015 1900. Garde, D. Lilly’s new insulin is likely DOA after latest delay, analyst says. http://www.fiercebiotech.com/story/lillys-new-insulin-likely-doa-after-latest-delay-analystsays/2015-02-23. Accessed 9/8/2015 Garde, D. Merck takes aim at Sanofi with a Lantus biosimilar of its own. http://www.fiercebiotech.com/story/merck-takes-aim-sanofi-lantus-biosimilar-its-own/2014-02-10. Accessed 10/3/2014 1400 Heinzman, S. ADA 2013. Sanofi will Maintain Dominance with U300. http://www.datamonitorhealthcare.com/ada2013_sanofi_u300_opinion/ Accessed 10/3/2014 1421 Holst, Jens Juul and Orskov, Cathrine. The Incretin Approach for Diabetes Treatment. Diabetes. December 2004. Vol. 53. No suppl 3 S197-S204. http://diabetes.diabetesjournals.org/content/53/suppl_3/S197.full. Accessed 8/12/2015 1441 http://www.humalog.com/humalog-u200-hcp.aspx. Accessed 9/8/2015 1838 The Incretin Effect. http://www.glucagon.com/incretineffect.html. Accessed 8/12/2015 1450. Inzucchi, S. et al. Management of Hyperglycemia in Type 2 Diabetes, 2015: A Patient-Centered Approach: Update to a Position Statement of the American Diabetes Associaton and the European Association for the Study of Diabetes. DiabetesCare. January 2015 38:1 140-149;doi:10.2337/dc14-2441 Irons, B. New Pharmacotherapies for Type 2 Diabetes. Pharmacotherapy Self Assessment Program 2013. Book 1. Cardiology/Endocrinology. American College of Clinical Pharmacy. 2013. pp5-21. Lowes, R. Diabetes Drug Empagliflozin (Jardiance) wins FDA OK on second try. http://www.medscape.com/viewarticle/829326. Accessed 10/15/2014 1527. Nainggolan, Lisa. First Biosimilar Insulin, Glargine, Approved in EU. Medscape Multispecialty. http://www.medscape.com/viewarticle/831441. Accessed 8/12/2015 1540. Palmer, Eric. Novo’s Tresiba news injects uncertainty in insulin market, particularly for Sanofi. http://www.fiercepharma.com/story/novos-tresiba-news-injects-uncertaintyinsulin-market-particularly-sanofi/2015-04-08. Accessed 8/13/15 0859 https://www.saxendapro.com/. Accessed 9/8/2015 1918 https://www.toujeo.com/?utm_source=google&utm_medium=cpc&utm_campaign=Brand-%20Toujeo_General_Exact&utm_term=toujeo_TJOCO23027WB_86184398-VQ660841520462-VQ15-1t1-VQ16-c&moc=TJOCO23027WB. Accessed 9/8/2015 1839 Tucker, M. FDA Approves Once-Weekly Dulaglutide for Type 2 diabetes. http://www.medscape.com/viewarticle/831969. Accessed 10/15/2014 1509. Tucker, M. FDA Approves Dapagliflozin (Farxiga) for Type 2 Diabetes Treatment. http://www.medscape.com/viewarticle/818858. Accessed 10/15/2014 1524. Tucker, M. FDA Rejects Novo Nordisk’s Insulin Degludec. http://www.medscape.com/viewarticle/779077. Accessed 9/8/2015 1906 Diabetes and Heart Research Center. http://dhrcindia.com/diabetes_e_10.html. Accessed 10/15/2014 1642