1. Consider this Combo: GLP-1 Receptor Agonists and Basal Insulin Matt Heinsen, PharmD PGY2 Pharmacotherapy Resident Butler University & Community Health Network This speaker has no actual or potential conflicts of interest to disclose in relation to this presentation

2. Discuss the rationale, benefits and literature behind combining glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and basal insulin Identify the place in therapy for combination basal insulin and GLP-1RAs Objectives

3. An Emerging Strategy American Diabetes Association. Diabetes Care. 2015;38(suppl 1):S1-93

4. An Emerging Strategy Endocrine practice 2015; 21(S1):1-64

5. Minimize weight gain Minimize risk of hypoglycemia Target treatment to both fasting and postprandial glucose Eliminate the need for prandial insulin Reduce insulin requirements Rationale for Basal Insulin and GLP-1RAs Trujillo JM and Nuffer W. Pharmacotherapy. 2014;34(11):1174-1186

6. Buse, et al. Buse, et al. Ann Intern Med. 2011;154:103-112 Study Design Randomized, double-blind, placebo-controlled Primary outcome: change in A 1 c Groups: exenatide 10 mcg SQ BID or placebo + insulin glargine Results A 1 c decreased 1.74% with exenatide and 1.04% in the placebo + insulin group Between group difference: -0.69% [CI, -0.93% to -0.46%], p < 0.001 Weight loss and less insulin required in exenatide group Applicability Improved glucose control with addition of GLP-1RA High incidence of GI AEs with GLP-1RAs

7. Diamant, et al. Study Design Randomized, open-label, noninferiority Primary outcome: change in A 1 c Groups: exenatide 5-10 mcg SQ BID or mealtime insulin lispro + insulin glargine Results Demonstrated noninferiority Between group difference in A 1 c was -0.04% [95% CI, -0.18% to 0.11%] Improved treatment satisfaction in exenatide group, p < 0.001 Applicability Support exenatide as a noninsulin addition for patients Short acting GLP-1RAs may be preferred over bolus insulin Diamant, et al. Diabetes Care. 2014;37:2763-2773

8. Rosenstock, et al. Study Design Randomized, open label, noninferiority Primary outcome: change in A 1 c Groups: albiglutide 30 mg SQ weekly (titrated up to 50 mg) or mealtime insulin lispro + insulin glargine Results Demonstrated noninferiority Between group difference in A 1 c was -0.16% [95% CI, -0.32% to 0.00%], p < 0.001 Hypoglycemia occurred twice as much in the insulin lispro group Applicability Once weekly GLP-1RA use simpler and effective Study limitations Rosenstock, et al. Diabetes Care. 2014;37(8):2317-2325

9. Patient Considerations Carris, et al. Drugs. 2014;74:2141-2152 Trujillo JM and Nuffer W. Pharmacotherapy. 2014;34(11):1174-1186 Need for additional A1c lowering Desire to avoid prandial insulin Concern for AEs: weight gain, hypoglycemia Cost considerations

10. Initiating GLP-1RA Therapy Carris, et al. Drugs. 2014;74:2141-2152 Empiric reduction of basal insulin Dose titration Adverse GI effects Caution in elderly Potential renal adjustments Use of delivery devices

11. Combination long acting insulin and GLP-1RA products Insulin degludec and liraglutide recently approved in Europe Insulin glargine and lixisenatide In the Pipeline...

12. Combination GLP-1 Receptor Agonists and Basal Insulin Matt Heinsen, PharmD PGY2 Pharmacotherapy Resident Butler University & Community Health Network Email: mheinsen@ecommunity.com