Are you ready for more insulin formulations? Shara Elrod, PharmD, BCACP, BCGP Learning Objectives Review pharmacology and dosing of new insulin formulations Compare and contrast new insulin formulations with usual care in patients with extreme insulin resistance Based on a patient case, calculate correct dosing of new insulin formulations 2 http://incedo.unthsc.edu 1
There are lots of new insulins! 3 T2DM Pathophysiology Diabetes 2009 Apr; 58(4): 773-795 4 http://incedo.unthsc.edu 2
Treatment of T2DM 5 Insulin Resistance Diabetes 2009 Apr; 58(4): 773-795 6 http://incedo.unthsc.edu 3
Generic (Brand Names) Regular insulin U-500 (Humulin U-500) Insulin glargine U-300 (Toujeo ) Insulin glargine and lixisenatide (Soliqua ) Insulin degludec (Tresiba ) Insulin degludec and insulin aspart (Ryzodeg 70/30) Insulin degludec and liraglutide (Xultophy 100/3.6) Insulin lispro U-200 (Humalog U-200) 7 Regular insulin U-500 Available since 1950s Increased popularity due to increases in insulin resistance and obesity Cheaper per unit than U-100 5x more concentrated than regular insulin U-100 Approved for use in continuous subcutaneous infusion insulin systems (i.e. insulin pumps) J Diabetes Sci Technol. 2012;6(2):412-420; Diabetes Care. 2011;34:2496 2501. 8 http://incedo.unthsc.edu 4
Regular insulin U-500 Similar onset of action to U- 100 Longer duration of action than U-100 Subcutaneous depot Similar to NPH Bolus that thinks it s a basal 9 Regular insulin U-500 Am J Health-Syst Pharm. 2010; 67: 1526-35. 10 http://incedo.unthsc.edu 5
Regular insulin U-500 11 Regular insulin U-500 Am J Health-Syst Pharm. 2010; 67: 1526-35. 12 http://incedo.unthsc.edu 6
Regular insulin U-500 Prescriber writes inject 30 units of U-500 insulin Do the directions mean Draw up 30 (actual) units of U-500 OR Draw up U-500 insulin up to the 30-unit mark on a U-100 syringe (corresponding to an actual insulin dose of 150 units) Avoid errors by Not using as directed or similar directions Writing insulin units AND unit markings for U-100 syringe Use U-500 syringe Am J Health-Syst Pharm. 2010; 67: 1526-35. 13 Regular insulin U-500 Insulin pen 500 units/ml; 3 ml/pen Each click is 5 units Patients should not count clicks Can give up to 300 units per injection 14 http://incedo.unthsc.edu 7
Checkpoint Question 1. When compared with regular insulin U-100, regular insulin U-500 has a: a) Similar onset of action and longer duration of action b) Similar onset of action and similar duration of action c) Longer onset of action and similar duration of action d) Longer onset of action and longer duration of action 15 Insulin degludec 16 http://incedo.unthsc.edu 8
Insulin degludec Ultra-long basal insulin Long duration of action (25-40 hours) More consistent profile Less nocturnal hypoglycemia versus glargine U-100 Once daily administration Flexibility in administration times Need at least 8 hours between doses Adjust doses every 3-4 days Diabetology & Metabolic Syndrome (2015) 7:57 17 Insulin degludec Only available as a pen 100 units/3 ml 300 units max of 80 units/injection 200 units/3 ml: odd number of units not allowed 600 units max of 160 units/injection In use pens can be used for up to 8 weeks Starting dose is 0.2 units/kg Insulin glargine U-100 recommended to start at 10 units or weight-based dosing 18 http://incedo.unthsc.edu 9
Insulin degludec Diabetology & Metabolic Syndrome (2015) 7:57 19 Insulin glargine U-300 Long-acting basal insulin 3x more concentrated than insulin glargine U-100 Only available as a pen 1.5 ml per pen 450 units per pen 80 units per injection Can substitute on a unit-to-unit basis for glargine U-100 Patients will likely need a higher U-300 dose to achieve glycemic goals Adjust dose every 3-4 days Longer duration of action versus glargine U-100, less nocturnal hypoglycemia Glargine U-100 up to 24 hours versus ~30 with U-300 20 http://incedo.unthsc.edu 10
Insulin glargine U-300 21 Insulin glargine U-300 Diabetes Care. 2015. 38:637-645. 22 http://incedo.unthsc.edu 11
Checkpoint Question 2. In comparison with insulin glargine U-100, insulin glargine U-300 has a: a) Shorter duration of action b) Similar duration of action c) Longer duration of action 23 Checkpoint Question 3. WH is a 57-year-old male newly diagnosed with type 2 diabetes mellitus (weight 110 kg). His hemoglobin A1c is 9.5% and he is complaining of increased hunger and thirst. Based on his clinical markers and insurance coverage, insulin glargine U-300 will be initiated. The correct starting dose of insulin glargine U-300 for WH is: a) 10 units b) 11 units c) 22 units d) 30 units 24 http://incedo.unthsc.edu 12
PK/PD Comparison Thera Clinic Risk Mgmt. 2016:12 389 400. 25 Insulin lispro U-200 Rapid acting insulin analog 2x more concentrated than insulin lispro U-100 Only available as an insulin pen 200 units/ml 3 ml insulin pen 600 total units per pen Up to 60 units per injection 1 unit per click In use pen must be used within 28 days Bioequivalent to insulin lispro U-100 at 20 units 26 http://incedo.unthsc.edu 13
Concentrated Insulin Pens 27 COMBINATION PRODUCTS 28 http://incedo.unthsc.edu 14
Insulin degludec and insulin aspart Approved by FDA in Sept 2015 Not yet launched in US Ultra-long acting plus bolus insulin (70/30) Ratio is fixed Cannot adjust basal vs prandial dosing 29 Insulin degludec and insulin aspart 30 http://incedo.unthsc.edu 15
GLP-1 agonists 31 Insulin degludec and liraglutide Ultra-long acting basal insulin plus GLP-1 agonist Should be administered at same time every day Without regard to meals Weight loss or maintain weight with no increase in hypoglycemia In use pens must be discarded after 21 days 16 units = 16 units of insulin degludec and 0.58mg liraglutide Max dose 50 units = 50 units of insulin degludec and 1.8 mg liraglutide 32 http://incedo.unthsc.edu 16
Insulin glargine U-100 and lixisenatide Long-acting basal insulin plus GLP-1 agonist Should be taken within 1 hour of 1 st meal of the day In use pens must be discarded after 14 days Nausea is a concern More common during initial treatment Can improve over time 33 Insulin glargine and lixisenatide Diabetes Care 2016 Nov; 39(11): 1972-1980. 34 http://incedo.unthsc.edu 17
Insulin glargine and lixisenatide 35 Conclusion Many new insulin formulations are available Some concern remains for adverse effects if products are not well known by prescribers Patients with high dose of less concentrated insulins may benefit from switching to more concentrated insulins Ultra-long acting basal insulins can provide a more consistent basal insulin profile and less hypoglycemia Basal insulins are now available with other type of injectables 36 http://incedo.unthsc.edu 18