Type 2 Diabetes Update For 2015

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Dorothy Webster
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1 Type 2 Diabetes Update For 2015 Jerry Meece, RPh, CDE, FACA, FAADE Plaza Pharmacy and Wellness Center jmeece12@cooke.net Learning Objectives At the conclusion of this presentation, the participant will be able to: 1. Review the role of 6 new drugs to treat Type 2 diabetes 2. Describe the mechanism of action the newest medications on the market for managing diabetes 3. List 4 indications, contraindications and precautions for 3 new classes of diabetes medications Challenges in Type 2 Diabetes Why The Need For More Drugs? Large number of patients Diabetes million people PREDIABETES 79 million people Weight gain (2 to 10 lbs) Progressive worsening of disease ( ability to secrete insulin) (Need to add more drugs) Controlling fasting and postprandial glucose Glucose fluctuations (variability) CDC National Diabetes Fact Sheet. US Department of Health and Human Services. Cefalu, WT. Am J Med. 2012;343(1): Diabetes: Here and Now Presentation downloaded from: 1

2 A Few More Reasons Managing complications and co-morbidities (balloon theory) Durability--sustaining optimal long-term glycemic control Hypoglycemia (Do we take it serious enough?) Durability How long does a oral med work? How do we know when it stops working? Variability: More Harm Than We Thought? Several studies to back up theory Needs more studies 2

3 Ideal Diabetes Drug No hypoglycemia No weight gain Well tolerated Good A1C lowering ability Given orally q d Helps with lipid profile and BP Low cost How Do We Choose A Drug What are the patient s glycemic goals? How far are they from these goals? What is their current diabetes regimen and/or what have they taken in the past? How long have they had diabetes? What is the principal problem? Fasting or postprandial Is there unacceptable risk from hypoglycemia Non glycemiceffects:cv,weight,lipids,bloodpressure Contraindications, special populations, comorbidities, etc. Cost What Is FDA Looking For In Approving A New Diabetes Medication? Low Incidence of Hypoglycemia Low CV risks Possible CV improvement 3

4 Hypoglycemia and Mortality Self-report or admission to ED for severe hypoglycemia is associated with 3.4-fold increased risk of death. HbA1c and Risk of Severe Hypoglycemia in Type 2 Diabetes: The Diabetes and Aging StudyKasia J. Lipska, E. Margaret Warton, Elbert S. Huang, Howard H. Moffet, Silvio E. Inzucchi, Harlan M. Krumholz, Andrew J. KarterDiabetes Care November; 36(11): T2DM: The 3-Legged Stool Nutrition Physical Activity Medications Blood Glucose Monitoring A1C = glycosylated hemoglobin, BP = blood pressure; HDL-C = high-density lipoprotein-cholesterol; LDL-C = low-density lipoprotein-cholesterol; TG = triglycerides American Diabetes Association (ADA). Diabetes Care. 2013;36(suppl 1):S11-S66. New Sites Of Action Six different sites Beta cells of pancreas Alpha cells Brain Muscle and adipose tissue Liver GI tract 4

5 GLP-1 Agonists Glucose dependent Decrease glucagon Increase Insulin from beta cells Delay absorption from stomach Decrease insulin resistance GLP-1 Agonists Exenatide Byetta Exenatide Extended Release Bydureon Thyroid C cell tumors Acute Pancreatitis? Once a week dosing vs daily dosing? liraglutide Victoza medullary thyroid carcinoma (MTC) New Indication of weight loss GLP-1 Agonists Dulaglutide Trulicity Medullary thyroid carcinoma Acute pancreatitis? Injection pen Albiglutide Tanzeum MTC Pancreatitis 5

6 DPP-4 Inhibitors Raise the drawbridge or lower the water? Protect a natural enzyme DPP-4, from breaking down GLP-1 DPP-4 Inhibitors Sitagliptin Alogliptin Saxagliptin Linagliptin Januvia Nesina Onglyza Trajenta What Once Was Bad In Some Cases Is OK Yesterday Today Glucose in Urine Glucose in Urine 1. Cowart SL, Stachura ME. In: Walker HK et al, eds. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd ed. Boston, MA: Butterworths; 1990:

7 Kidney and Glucose Produces glucose Utilizes glucose Filters glucose Reabsorbs glucose Normal Renal Handling of Glucose Sodium-Glucose Co-transporters (SGLT2s) 180 g/day/1.73 m 2 (filtered glucose load) 1 SGLT2 transports 90% of filtered glucose out 1-4 SGLT1 transports the remaining 10% 1-4 SGLT = sodium-glucose co-transporter. 1. Wright EM et al. J Intern Med. 2007;261(1): Kanai Y et al. J Clin Invest. 1994;93(1): You G et al. J Biol Chem. 1995;270(49): Wright EM. Am J Physiol Renal Physiol. 2001;280(1):F10-F18. Normal Kidney: Glucose Reabsorption (Plasma Glucose 180 mg/dl) Glucose reabsorption into systemic circulation Adapted with permission from Rothenberg PL et al. SGLT = sodium-glucose co-transporter. 1. Kanai Y et al. J Clin Invest. 1994;93(1): You G et al. J Biol Chem. 1995;270(49): Rothenberg PL et al. Poster presented at: 46th European Association for the Study of Diabetes Annual Meeting; September 20-24, 2010; Stockholm, Sweden. 7

8 Urinary glucose excretion (g/day) Urinary glucose excretion (g/day) 4/20/2015 SGLT2 Inhibitors Reduce Renal Glucose Reabsorption and Increase Urinary Glucose Excretion Glomerulus Proximal Convoluted Tubule Early Distal Glucose in urine Decreased glucose reabsorption into systemic circulation Glucose SGLT2 SGLT2 inhibitor SGLT1 Adapted with permission from Rothenberg PL et al. SGLT = sodium-glucose co-transporter. 1. Rothenberg PL et al. Poster presented at: 46th European Association for the Study of Diabetes Annual Meeting; September 20-24, 2010; Stockholm, Sweden. 2. Cowart SL, Stachura ME. In: Walker HK et al, eds. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd ed. Boston, MA: Butterworths; 1990: Abdul-Ghani MA, DeFronzo RA. Endocr Pract. 2008;14(6): Oku A et al. Diabetes. 1999;48(9): Renal Threshold for Glucose Excretion (RT G ) 125 in Healthy Adult Subjects Healthy 180 mg/dl 50 RT G Plasma glucose (mg/dl) 1. Cowart SL, Stachura ME. In: Walker HK et al, eds. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd ed. Boston, MA: Butterworths; 1990: Abdul-Ghani MA, DeFronzo RA. Endocr Pract. 2008;14(6): Nair S, Wilding JP. J Clin Endocrinol Metab. 2010;95(1): a Renal Threshold for Glucose Excretion Is Increased in T2DM 125 Renal glucose reabsorption is increased in T2DM 100 Healthy T2DM 180 mg/dl 240 mg/dl RT G RT G Plasma glucose (mg/dl) T2DM = type 2 diabetes mellitus. 1. Cowart SL, Stachura ME. In: Walker HK et al, eds. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd ed. Boston, MA: Butterworths; 1990: Abdul-Ghani MA, DeFronzo RA. Endocr Pract. 2008;14(6): Nair S, Wilding JP. J Clin Endocrinol Metab. 2010;95(1): INVOKANA [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc.;

9 The Flozin Family Canagliflozin Invokana Dapagliflozin Farxiga Empagliflozin Jardiance Limitations of SGLT2 Inhibitor Therapy Increased risk of genito-urinary infections Increase in UTIs but treatable, with no recurrence Increased mycotic genital infections, more so in women or with history of genital infections Risk of dehydration Some dehydration in patients with very high glucose levels ( osmotic diuresis) Very few cases of dehydration reported Electrolyte disturbances--hyperkalemia Potassium-sparing diuretics Group Considerations Caution in Elderly patients at risk of dehydration Women with history of infections Compromised renal function Stage 3 or 4 of chronic kidney disease 9

10 Actoplus MET Avandamet Duetact Glucovance Metaglip Kazano Oseni Prandimet. Combo Drugs metformin/pioglitazone rosiglitazone/metformin glimepiride/pioglitazone Glyburide/metformin metformin/glipizide metformin/alogliptin Alogliptin/pioglitazone repaglinide/metformin Other New Combos dapagliflozin/metformin Xigduo canagliflozin Invokamet/metformin New Insulins Insulin Glargine Injection Toujeo-300 True 24 hour Unit for unit for pens Versus U-500? Inhaled Human Insulin Afrezza Ultra rapid acting (peaks min) Duration 2-3 hours Easy To Teach 10

11 Inhaled Human Insulin--Afrezza Candidates : Who? When? Metformin not tolerated (approx. 15%) 1 Metformin no longer works Add on to initial oral therapy (2 nd or 3 rd ) Added to basal + with or without metformin? Need of added benefits of weight loss (or weight neutral) and and slightly above goal for hypertension 1 Parulkar AA, Pendergrass ML, Granda-Ayala R, Lee TR, Fonseca VA: Nonhypoglycemic effects of thiazolidinediones. Ann Intern Med 134:61 71, 2001 Patient Case: Roy Presentation: 47 yr old AA male Type 2 Dm x 8 yr Social/Lifestyle Hx: Truck Driver x 20 yrs. Limited P/A and lots of fast food Wt loss of 5 lbs in last month due to trying to eat smarter and just working harder at it A trial on a sulfonylurea caused frequent hypoglycemia due to erratic eating habits and he refuses any kind of shots. Diabetes Self-Management: Checks 3-4 times a week at different times FPG avg 139 mg/dl PPG avg 188 mg/dl Hx, Physical Lab: Ht/Wt: lb, BMI 28.5 BP 145/84 mm Hg HbA1c 7.9 % Serum Creatinine 1.2 mg/dl Microalbumin < 30mg/L Meds: Enalapril 10mg q d Atorvastatin 20mg q d Metformin 1000mg bid ASA 81 mg d What would be the next diabetes medication you would add to Roy s regimen? 11

12 Coming Down The Pipe? Newer Insulins? More orals??? Artificial Pancreas? 12

Clinical Assistant Professor. Clinical Pharmacy Specialist Wesley Family Medicine Residency Program. Objectives

Clinical Assistant Professor. Clinical Pharmacy Specialist Wesley Family Medicine Residency Program. Objectives What s New in Diabetes Medications? Matthew Kostoff, PharmD, BCPS, BCACP Clinical Assistant Professor Clinical Pharmacy Specialist Wesley Family Medicine Residency Program Objectives Discuss new literature