Care of the Patient with Diabetes in the Safety Net UCSF CME Care - PDF document

2/22/20 Care of the Patient with Diabetes in the Safety Net UCSF CME Care of Vulnerable Populations Elizabeth J. Murphy, MD, DPhil February 22, 2020 I have no financial interests or relationships to disclose. 1

2/22/20 Case 43 yo Hispanic man with obesity and newly diagnosed DM2 (no CKD or CAD) presents to your clinic. He was recently seen seen in the ED with an A1C of 13 and glucose of 575. He got treated and was given a prescription for Lantus and metformin. Now he comes to see you. He’s taking metformin and stopped soda but couldn’t afford his Lantus. Random BG 325. You decide he needs insulin and more orals meds. What do you do? a) Switch him to NPH which is covered but feel badly about it. b) Happily switch him to NPH. c) Fill out a PA to get him glargine. d) Give him a coupon or get him free glargine some other way 3 Case In addition to insulin and metformin you will add: a) A sulfonylurea but feel badly about it b) Happily add a sulfonylurea c) I don’t like SU so I’ll use some combination of other oral meds if I don’t have to fill out a PA to get them d) I don’t like SU so I’ll use some combination of other oral meds even if I have to fill out a PA e) Add a GLP-1 analog f) None of the above. I’ll just start with insulin and metformin. 4 2

2/22/20 A1C COST 10/2019 Sulfonylurea 1-2% $5 Metformin 1-2% $4 Pioglitazone 0.5-1.5% $20 TZD Exenatide 0.5-1.5% $731 $450 GLP-1 agonist Canagliflozin 0.5-0.8% $330 SGLT2i $498 DPP-IVi Sitagliptin 0.5-0.8% $320 $455 Acarbose 0.5-0.8% $30 5 JAMA Intern Med. 2019;179(10):1376-1385. doi:10.1001/jamainternmed.2019.2396 3

2/22/20 RETAIL PRICE HUMOLOG (LISPRO) $300 $250 $200 $150 $100 $50 $- 1995 2000 2005 2010 2015 2020 A1C COST 10/2019 Good Rx.com 10/2014 Sulfonylurea 1-2% $5 Metformin 1-2% $4 Pioglitazone 0.5-1.5% $20 TZD Exenatide 0.5-1.5% $450 $731 GLP-1 SGLT2i Canagliflozin 0.5-0.8% $330 $498 DPP-IV Sitagliptin 0.5-0.8% $320 $455 Acarbose 0.5-0.8% $30 8 4

2/22/20 PIOGLITAZONE • In some patients has profound A1C lowering without hypoglycemia when used alone. • It can take a month or more to see effects. • Absolutely contraindicated in CHF. • Long term adverse bone effects and may increase risk of bladder cancer in men. DPPIV Inhibitors • Horrible at A1C lowering. • Don’t have the weight loss benefits of GLP-1 agonists. • May have unexpected AE • If it’s not working don’t continue it. 5

2/22/20 Concerns with Inexpensive DM Meds • Metformin – Renal failure, congestive heart failure, gastrointestinal side effects • Sulfonylureas – Increased cardiovascular risk – Hypoglycemia (low blood sugar) • Insulins – Hypoglycemia DO SULFONYLUREAS INCREASE RISK OF CARDIOVASCULAR DISEASE? 12 6

2/22/20 MEDPAGE TODAY 7

2/22/20 Forest plot summarising the primary analysis and all sensitivity analyses Antonios Douros et al. BMJ 2018;362:bmj.k2693 77,138 Metformin Monotherapy Users 25,699 Adding or switching to SU 13,217 9,800 Switching to SU Adding SU 8

2/22/20 Adjusted HR Myocardial Infarction (95% CI) Adding SU Switching to SU Ischemic Stroke Adding SU Switching to SU CV Death Adding SU Switching to SU All Cause Mortality Adding SU Switching to SU 0.5 2.5 4.5 6.5 8.5 Stopping Metformin Increases the Risk of Cardiovascular Disease Adding a sulfonylurea to metformin does not increase the risk of cardiovascular disease but replacing metformin with a sulfonylurea does 9

2/22/20 GLARGINE (LANTUS) COMPARED TO NPH a) Lowers A1C more b) Has less clinically significant hypoglycemia c) Both d) None of the above Name Brand Status Manufacturer Cost Name glargine Lantus Sanofi $278-429 glargine Basiglar Biosimilar Lilly $235-331 glargine Lusduna Biosimilar Merck Not available glargine Toujeo U-300 Sanofi $295-393 detemir Levemir Novo Nordisk $446-465 degludec Tresiba Novo Nordisk $490-511 NPH (vial) Humulin Lilly NA-$474 NPH (pen) Humulin Lilly $301 NPH (vial) Novolin Novo Nordisk $24-144 Good Rx.com 2018 and 5/2019 10

2/22/20 Insulin Degludec • Has a much longer duration of action than glargine • More flexible about what time of day it is given • May be useful in patients with DM1 with poor med adherence who might not remember to take insulin every day to prevent DKA Name Brand Status Manu-facturer Cost Name aspart Novolog Novo Nordisk $300-560 aspart Fiasp Novo Nordisk NA-$294 glulisine Apidra Sanofi $423-551 lispro Humalog Lilly $178 -$334 lispro (vial) Admelog Biosimilar/ Sanofi $470-239 Interchangeable lispro “generic” Lilly NA - $137 R (vial) Humulin Lilly $99-155 R (vial) Humulin Novo Nordisk NA-$144 R (pen) Humulin Lilly $578 R (pen) Kwikipen U-500 Lilly ? $540 Good Rx.com 2018 and 5/2019 11

2/22/20 Name Manufacturer Cost 70/30 70 N/30 R Novo Nordisk/Lilly $300-560 70/30 70 N/30 aspart Novo Nordisk NA-$294 (Novolog) 75/25 70N/25 lispro Lilly $423-551 (Humalog) 50/50 50N/50R Novo Nordisk/Lilly $178 -$334 lispro (vial) Biosimilar/ Sanofi $470-239 Interchangeable R (pen) U-500 Lilly ? - $540 Good Rx.com 2018 and 5/2019 Advantages of Insulin Analogues – in DM2 § Rapid acting insulin o Better mimics human physiology o Improved A1C o Fewer lows § Long acting analogues o Fewer lows o Less of a peak o Take fewer shots in basal bolus o Better A1C 24 12

2/22/20 Advantages of Insulin Analogues – in DM2 § Rapid acting insulin o Better mimics human physiology? o Improved A1C o Fewer lows § Long acting analogues o Fewer lows o Less of a peak o Take fewer shots in basal bolus o Better A1C 25 Cochraine Review NPH versus Basal Analogues • 6 studies comparing glargine to NPH • 2 studies comparing detemir to NPH • A1C and adverse effects did not differ in a clinically relevant way. • No difference for severe hypoglycemia • Statistically significant lower rates of nocturnal hypoglycemia with glargine/detemir with target glucose < 100 • No effect on mortality, morbidity, QOL Horvath et al, Cochrane Database of Systematic Reviews 2007, Issue 2. Art. No.: CD005613. DOI: 10.1002/14651858.CD005613.pub3 13

2/22/20 ED visits or Hospital Admissions for Hypoglycemia with Basal Insulin Analogs vs NPH in Type 2 Diabetes JAMA. 2018;320(1):53-62. doi:10.1001/jama.2018.7993 Reduction in A1C * 1.48 1.26 NPH Insulin Analogs JAMA. 2018;320(1):53-62. doi:10.1001/jama.2018.7993 14

2/22/20 Advantages of Insulin Analogues – in DM2 § Rapid acting insulin o Better mimics human physiology? o Improved A1C o Fewer lows § Long acting analogues o Fewer lows (clinical relevance???) o Less of a peak ? o Take fewer shots in basal bolus (depends) o Better A1C 29 Advantages to NPH • Can be used as a bridge to correct once daily basal dose timing. • It can be adjusted twice a day allowing for more rapid titration to goal • Allows for more basal insulin in the day for snackers • Allows for more basal insulin during the day for steroid induced hyperglycemia which preferentially results in peripheral insulin resistance • Allows for less basal insulin at night with renal failure/cirrhosis • May be more affordable for patients 15

2/22/20 Viewpoint E d July 4, 2017 i t o r i a J l u Human Insulin for Type 2 Diabetes l y 3 , 2 0 Revisiting NPH Insulin for Type 2 Diabetes 1 8 An Effective, Less-Expensive Option Is a Step Back the Path Forward? Kasia J. Lipska, MD, MHS 1 ; Irl B. Hirsch, MD 2 ; Matthew C. Riddle, MD 3 Matthew J. Crowley, MD, MHS 1,2 ; Matthew L. Maciejewski, PhD 1,3,4 JAMA. 2017;318(1):23-24. doi:10.1001/jama.2017.6939 J A M A . 2 0 1 8 ; 3 2 0 ( 1 ) : 3 8 - 3 9 . d o i : 1 0 . 1 0 0 1 / j a m a . 2 0 1 8 . 8 0 3 3 16

2/22/20 The Sunshine Act 2018 Starting Insulin • On average 3 year delay between needing and starting insulin • Insulin resistance 17

2/22/20 Insulin Start Groups • 2 hr “insulin introduction” groups • Facilitated by advance practice nurses and patients on insulin • First hour addressing fears, myths • Second hour hands on teaching, mock injection A1C Reduction Spanish Group 11.0% 10.5% * 10.0% ** Baseline 9.5% English Group 6 months 9.0% 11.0% 8.5% 10.5% 8.0% Insulin group Usual Care 10.0% * ** 9.5% Baseline 6 months 9.0% * P < 0.05 compared to baseline 8.5% ** P < 0.001 compared to baseline 8.0% Insulin group Usual Care Kuo et al, J Clin Nurs. 2017, 1705-1713. doi: 10.1111/jocn.13577. 18

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2/22/20 INSULIN INTRO VIDEO ENGLISH http://bit.ly/InsulinIntro-Eng INSULIN INTRO VIDEO SPANISH http://bit.ly/InsulinIntro-Spa Glycemic Targets Over the Years 9% 8% Before DCCT, 7% UKPDS After DCCT After DCCT, UKPDS Sulfonylurea + Metformin + TZD Insulin 1980s 1990s 1997 20

2/22/20 DCCT/EDIC - Cumulative Incidence CVD Outcomes 42% reduction in CVD risk 57% reduction in risk of nonfatal MI, stroke or CVD death 8.0 v 8.1 % A1C [----------------------------------------------] At 30 y Follow up 30% reduction in CVD risk 32% reduction in risk of nonfatal MI, stroke or CVD death 7.2 v 9.1 % A1C N Engl J Med 2005;353:2643-2653 Glycemic Targets Over the Years 9% 8% Before DCCT, 7% UKPDS 7% After DCCT ? 6% After After DCCT, ACCORD UKPDS Sulfonylurea + Metformin + TZD + Incretin + Mortality Insulin 2008 1980s 1990s 1997 2006 21