GROWING OUR FUTURE IN DIABETES CARE: WHERE ARE WE NOW AND WHERE ARE WE GOING? Ashley Firm, Pharm.D. Lindsey Meston, Pharm.D. Disclosure Neither Dr. Firm nor Dr. Meston have anything to disclosure concerning possible financial or personal relationships with commercial entities (or their competitors) mentioned in this presentation. Objectives ■ Summarize key differences and updates to guidelines related to the care of diabetic patients, especially updates in the 2018 American Diabetes Association Standard of Medical Care in Diabetes ■ Select most appropriate treatment regimens for sample patients based on diabetic presentation and co-morbid conditions ■ Evaluate new products to the market for the treatment of diabetes, including place in therapy, pros and cons of use, major adverse effects, and other pertinent pharmacokinetic and pharmacodynamic properties. SOC-36238233 Socrative Join Code Which of the following correctly pairs a basal insulin and GLP1-RA coformulation? A. Insulin glargine- semaglutide B. Insulin determir- dulaglutide C. Insulin degludec- liraglutide Which new agent was accepted by the FDA for regulatory filing as a dual inhibitor of SGLT-2 in the treatment of type 1 diabetes? A. Sotagliflozin B. Empagliflozin C. Dapagliflozin D. Canagliflozin Under the ADA Standards of Care 2018, a patient with a history of a myocardial infarction would be recommended for which class of medication in addition to metformin? A. Thiazolidinediones B. Sulfonylureas C. Sodium Glucose Co-Transporter 2 Inhibitor D. Alpha Glucosidase Inhibitor Under the updated guidelines of the American Association of Clinical Endocrinologists, a patient failing to achieve A1C goal with metformin would be most appropriately treated with a medication from which class? A. Glucagon-like Peptide 1 Receptor Agonist B. Meglitinides C. Bolus insulin D. Amylin Analog Diabetes in America ■ According to the CDC, more than 30 million Americans have diabetes – 1 in 4 don’t even know – Total direct and indirect cost is more than $240 billion/year – Seventh leading cause of death in the United States in 2015 ■ According to the American Diabetes Association, 1 in 3 Americans has prediabetes – That's more than 84 million Americans! – 90% of these patients do not know their risk https://www.cdc.gov/diabetes/basics/quick-facts.html National Diabetes Statistics Report, 2017 Diabetes in America ■ In the last 20 years, the number of diagnosed cases of diabetes has tripled as the population has aged CDC's Division of Diabetes Translation. United States Diabetes Surveillance System. http://www.cdc.gov/diabetes/data Diabetes in America Sotagliflozin Dapagliflozin/metformin Lixisenatide *Pending approval 10/2014 7/2016 2019 dapagliflozin/saxagliptin empagliflozin/metformin 2/2017 8/2015 Insulin degludec/liraglutide Empagliflozin/linagliptin Insulin glargine/lizisenatide 2/2015 11/2016 Semaglutide Ertugliflozin Insulin degludec Ertugliflozin/metformin Insulin degludec/insulin aspart Ertugliflozin/sitagliptin 9/2015 12/2017 NEW MEDICATIONS NEW INDICATIONS ■ Regular Insulin U-500 Pen ■ Insulin Lispro U-200 Pen Insulin and Insulin Changes ■ Insulin Glargine U-300 Pen ■ Insulin Degludec (Tresiba) Regular Insulin U-500 Pen ■ Class – Regular Insulin (Humulin-R) ■ Delivery Method – Kwikpen – U-500 syringes ■ Clinical Pearls – Useful for severely insulin-resistant patients requiring >200 units/day – Contains both basal and prandial properties ■ Can be used as monotherapy ■ Requires 2-3 injections per day – Can reduce insulin volume by 80% compared to U-100 Regular Insulin U-500 Vial and Syringe Pen ■ Syringe calibrated for 500U/1ML ■ Dial doses in increments of 5 units ■ No conversion needed ■ No conversion needed ■ Reduced risk for dosing errors ■ Reduced risk for dosing errors ■ Use with 20ml vial ■ Ease of administration with pens ■ 1500 units/3 ml pen, 2 pens per box https://www.humulin.com/hcp/delivery-options.aspx#u-500-kwikpen Insulin Lispro U-200 Pen ■ Class – Rapid Acting Insulin (Humalog) ■ Delivery Method – 200 units/1ml pen, can dial doses in 1-unit increments – Max dose per injection is 60 units – Box contains 2 x 3ml pens ■ Clinical Pearls – Rapid-acting meal time insulin given 15 minutes before a meal – One-half the volume of U-100 insulins – Consider switching when meal time insulin needs >20 units/meal – No dosing conversion needed from U-100 to U-200 https://www.humalog.com/hcp/humalog-u200/ Insulin Lispro Junior Pen ■ Class – Rapid acting insulin (Humalog Junior) ■ Delivery Method – Insulin lispro pen device delivering 0.5-unit increments! ■ Clinical Pearls – Self- contained delivery unit only requiring an additional pen needle – Can dial between 0.5 units and 30 units per injection https://www.humalog.com/hcp/humalog-u100-and-junior-kwikpen/#junior_kwikpen Insulin Lispro U-100 ■ Class - Rapid-acting insulin (Admelog) ▪ "Follow on" to Humalog ■ Delivery Method - Available in Solostar or vial ▪ Discard open insulin after 28 days ■ Clinical Pearls - Identical amino acid sequence to Eli Lilly insulin lispro leading to similar PK profile - 1:1 dosing conversion from other insulin lispro products - ADE: similar to other rapid acting insulins- hypoglycemia, hypokalemia, lipodystrophy Insulin Aspart U-100 ■ Class – Rapid-acting insulin (Fiasp) ■ Delivery Method – Available in Flextouch or vial ▪ Max 80 units per injection with pen ▪ Discard open insulin after 28 days ■ Clinical Pearls – Insulin aspart with two excipients allowing ultra-rapid acting characteristics ▪ Enters blood stream in ~2.5 minutes ▪ Can be taken with start of meal or within 20 minutes of starting – 1:1 dosing conversion from other rapid acting insulin products – Not approved for pediatric population – ADE: similar to other rapid acting insulins- hypoglycemia, hypokalemia, lipodystophy Insulin Glargine U-300 Pen ■ Class – Basal insulin (Toujeo Max Solostar) ■ Delivery Method – Same insulin glargine U-300 in original pen device – Pen device has changed to hold 900 units of insulin per pen – Packages as 2 x 3ml pens – Dose 2-160 units per injection ■ Clinical Pearls – Insulin glargine U-100 to U-300 conversion- 1:1 – 42-day expiration after opening, removal from refrigeration Insulin Degludec ■ Class – Basal Insulin (Tresiba) ■ Delivery Method – Available as U-100 or U-200 insulin pens ■ Clinical Pearls – Unique PK: T ½ 25 hours ■ Provides 42-hour coverage ■ Allows for a more flexible dosing schedule – 1:1 dose conversion from other basal or intermediate insulins – Insulin naïve patients: start with 10 units nightly DEVOTE Trial ■ Non-inferiority safety outcomes trial in risk of major cardiovascular events (MACE) with insulin degludec U-100 compared to insulin glargine U-100 ■ Treat to target study design of 7600+ patients with inadequately controlled diabetes and atherosclerotic cardiovascular disease ■ Primary endpoint: time to first MACE – 8.5% in degludec group vs 9.3% in glargine group ■ Secondary confirmatory endpoint: number and incidence of severe hypoglycemic events Insulin degludec/ insulin aspart ■ Class – basal insulin/ rapid acting insulin combination (Ryzodeg) ■ Delivery Method – Available in Flextouch pens – 0.7 units insulin degludec and 0.3 units insulin aspart in each 1 unit of insulin ■ Clinical Pearls – Unlike other mix insulins, solution should be clear and cloudless – Titrate to goal basal dosing- may need to supplement bolus doses ■ Place in Therapy (PiT): reduce needle sticks by combining injections ■ Samaglutide New Non-insulin ■ Lixisenatide Therapies ■ Sotagliflozin ■ Ertugliflozin Semaglutide injection ■ Class – Glucagon-like peptide-1 receptor agonist (Ozempic) ■ Delivery Method – Different pens for 0.25 and 0.5mg doses vs 1mg doses – Dosing ■ 0.25mg SQ weekly x 4 weeks ■ Week 5: Increase to 0.5mg SQ weekly ■ Week 9: May increase to 1mg SQ weekly ■ Clinical Pearls – Take missed dose if remember within 5 days – Adverse Drug Effects (ADE): Nausea, vomiting, diarrhea, abdominal pain, constipation – Warnings: possible thyroid tmors, including cancer Semaglutide injection ■ Semaglutide outperformed dulaglutide in head-to-head A1C lowering (SUSTAIN 7) – 40 weeks, randomized, open-label, active control of 1201 adults – Semaglutide 0.5mg vs dulaglutide 0.75mg ■ A1C lowered 1.4% vs 1.1% (baseline 8.2 vs 8.3) – Semaglutide 1mg vs dulaglutide 1.5mg ■ A1C lowered 1.6% vs 1.3% (baseline 8.2) ■ Semaglutide outperfomed sitagliptan and exenatide extended release in head-to-head A1C lowering (SUSTAIN 2 & SUSTAIN 3) Semaglutide Injection ■ Semaglutide was evaluated for CV safety in a 2-year cardiovascular outcomes trial (CVOT) ■ SUSTAIN 6- 104 week, randomized, multinational, multicenter, double blind, placebo controlled, parallel group, noninferiority, CV safety trial of 3297 adults – Randomized 1:1:1:1 to semaglutide 0.5mg or 1 mg or plaecbo 0.5 or 1mg – All received Diabetes and cardiovascular standards of care – Primary endpoint: first occurance of MACE ■ Standard of care: 8.9% ■ Semaglutide: 6.6% ■ No additional clinical studies establishing reduction in MACE Lixisenatide Injection ■ Class – GLP-1 Receptor Antagonist (Adlyxin in US, Lyxumia in EU) ■ Delivery Method – Dosing: Starter pack of 10 mcg SQ daily for 14 days then increase to 20 mcg SQ daily (Starter pack contains one 10mcg pen and one 20mcg pen) – Maintenance pack contains two 20mcg pens ■ Clinical Pearls – MACE: no reduction shown – Similar ADE and warnings to other members of the class Sotagliflozin ■ FDA has accepted regulatory filing with a target action date of March 2019 ■ Class – Oral dual inhibitor of SGLT-1 and