Disclosure GLP-1 Agonists and I have no conflicts of interest to disclose. Long-Acting Insulin Combination Therapy Jeanna Sewell, PharmD, BCACP Assistant Clinical Professor Auburn University Harrison School of Pharmacy Objectives Long-Acting Insulin Lantus ® (insulin glargine) . Lower blood glucose At the end of this presentation, the audience should be (BG) throughout the able to: day Explain the mechanism of GLP-1 agonists Levemir ® (insulin detemir) . Does not target Identify advantages and disadvantages of combination GLP-1 post-prandial BG agonists and long-acting insulin combination products (PPBG) Discuss the potential role in therapy of GLP-1 agonist and long- acting insulin combination products Toujeo ® (insulin glargine U-300) . Dosed once or twice daily Tresiba ® (insulin degludec) Glucagon-like Peptide-1 Agonists (GLP-1) GLP-1 Receptor Agonists exenatide (Byetta®, Bydureon®) Benefits: Weight loss Glucose-dependent mechanism liraglutide (Victoza®) Lower A1C 1-1.5% Side effects: Nausea, HA, diarrhea albiglutide (Tanzeum®) Pancreatitis BBW: Medullary thyroid carcinoma TM Multiple endocrine neoplasia syndrome 2 dulaglutide (Trulicity ) (MEN2) Lixisenatide (Adlyxin®) Image from http://www.gastrojournal.org/article/S0016-5085(07)00580-X/fulltext?refuid=S0002-8223(09)02093-8&refissn=0002-8223 Potential Role in Therapy Soliqua (insulin glargine and lixisenatide) ADA Standards of Care 2017 Available in retail pharmacies January 2017 Safety FDA Approved Indication: patients with Type 2 diabetes who are uncontrolled on basal insulin (<60 units per day) or lixisenatide Efficacy Formulation: Fixed dose insulin glargine 100 units/mL and lixisenatide 33 micrograms/mL Maximum Daily Dose: 60 units insulin glargine/20 mcg of lixisenatide Xultophy (insulin degludec and liraglutide) Combination Therapy Advantages Disadvantages Available in retail pharmacies May 2017 Once daily injection Maximum dosage FDA Approved Indication: Once daily as adjunct to diet and exercise in Works on fasting and post- Cost prandial blood glucose patients with Type 2 diabetes inadequately controlled on basal insulin Side effects from GLP-1 (<50 units/day) or liraglutide Lower risk of hypoglycemia Formulation: Fixed dose insulin degludec 100 units/mL and liraglutide Weight loss 3.6 mg/mL Starting: 16 units/0.58 mg liraglutide Maximum Daily Dose: 50 units insulin degludec/1.8 mg liraglutide Conclusion Question 1: Which of the following is an advantage of the use of a GLP1 receptor agonist in type 2 diabetes? GLP-1 agonists are effective therapies for treatment of type 2 diabetes a) Weight loss GLP-1 agonist and long-acting insulin combination therapies may have a role in therapy in treatment of type 2 diabetes b) Improvement in fasting blood glucose Uptake into practice still to be determined c) Lack of GI side effects Question 1: Which of the following is an Question 2: What is a disadvantage of the use advantage of the use of a GLP1 receptor of a GLP1 + LA insulin combination therapy agonist in type 2 diabetes? when compared to LA insulin + bolus insulin? a) Excess hypoglycemia a) Weight loss b) Maximum dose b) Improvement in fasting blood glucose c) Weight gain c) Lack of GI side effects Question 2: What is a disadvantage of the use Question 3: Which of the following patients of a GLP1 + LA insulin combination therapy would the most appropriate candidate for the when compared to LA insulin + bolus insulin? use of a GLP1 + LA insulin combination therapy? a) Excess hypoglycemia a) 45 yo M with A1C 8.2% on Lantus 20 units once daily and metformin 1000 mg twice daily b) Maximum dose b) 62 yo F with A1C 6.5% on metformin 1000 mg twice daily c) Weight gain and empagliflozin 10 mg once daily c) 36 yo M with A1C 9.0% Lantus 40 units twice daily Question 3: Which of the following patients References would the most appropriate candidate for the Lexicomp Online. Hudson, Ohio: Lexi-Comp, Inc.; September 10, 2017. Standards of medical care in diabetes – 2017. American Diabetes Association. use of a GLP1 + LA insulin combination Diabetes Care 2017. 40(1);Jan 17. therapy? Rhinehart AS. Adding GLP-1 Receptor Agonist Therapy to Basal Insulin for Postprandial Glucose Control. Clinical Diabetes : A Publication of the American Diabetes Association. 2015;33(2):73-75. doi:10.2337/diaclin.33.2.73. a) 45 yo M with A1C 8.2% on Lantus 20 units once daily Rosenstock J, Fonseca VA, Gross JL, et al. Advancing basal insulin replacement in and metformin 1000 mg twice daily type 2 diabetes inadequately controlled with insulin glargine plus oral agents: a comparison of adding albuglutide, a weekly GLP-1 receptor agonist, versus thrice- daily prandial insulin lispro. Diabetes Care. 2014 Aug;37(8):2317-25. doi: 10.2337/dc14-0001. Epub 2014 Jun 4. b) 62 yo F with A1C 6.5% on metformin 1000 mg twice daily Eng C, Kramer CK, Zinman B, Retnakaran R. Glucagon-like peptide-1 receptor agonist and basal insulin combination treatment for the management of type 2 and empagliflozin 10 mg once daily diabetes: a systematic review and meta-analysis. Lancet. 2014 Dec 20;384(9961):2228-34. doi: 10.1016/S0140-6736(14)61335-0. Epub 2014 Sep 11. Diamant M, Nauck MA, Shaginian R, et al. Glucagon-like peptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes. Diabetes Care. c) 36 yo M with A1C 9.0% Lantus 40 units twice daily 2014 Oct;37(10):2763-73. doi: 10.2337/dc14-0876. Epub 2014 Jul 10..