Quick Guide MEDICATIONS 7th Edition Evan Sisson, Pharm.D., MHA, CDE

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1 Quick Guide to MEDICATIONS 7th Edition Evan Sisson, Pharm.D., MHA, CDE Adapted from The Art and Science of Diabetes Self-Management Education Desk Reference

2 2017, American Association of Diabetes Educators, Chicago, Illinois. Editions: 2016, 2014, 2010, 2008, 2005, 2004 All rights reserved. No part of this publication may be reproduced electronically or mechanically, stored in a retrieval system, or transmitted in any form or by any means. The information contained in these files may not be copied to a diskette, mounted to a server, or otherwise distributed in any form without the express written permission of the American Association of Diabetes Educators. Printed and bound in the United States of America. The views expressed in this publication are those of the authors and do not necessarily reflect the policies and/or official positions of the American Association of Diabetes Educators. Mention of product names in this publication does not constitute endorsement by the authors or by the American Association of Diabetes Educators. The American Association of Diabetes Educators and its officers, directors, employees, agents, and members assume no liability whatsoever for any personal or other injury, loss, or damage that may result from the application of the information contained herein

3 Table of Contents Introduction v Glycemic Control 1 First-Generation Sulfonylureas 3 Second-Generation Sulfonylureas 4 Nonsulfonylurea-Secretagogues 5 Biguanides 5 Thiazolidinediones 7 Alpha-Glucosidase Inhibitors 7 Ergot Derivatives 8 Amylin Analog 8 Bile Acid Sequestrants 8 DPP-4 Inhibitors 9 Incretins 11 SGLT2 Inhibitors 13 Fixed-Dose Combinations 15 Insulin 17 Insulin Available in the US 17 Comparison of Human Insulin Preparations and Analogs 19 Guidelines for Mixing Insulin and Pre-filling Syringes 20 Rapid-Acting Inhaled Insulin 21 Starting Insulin in Adults with Type 1 Diabetes 22 Starting Insulin in Children with Type 1 Diabetes 24 Starting Insulin in Adults with Type 2 Diabetes 25 Blood Pressure Control 27 Recommendations for Blood Pressure Control in Patients with Diabetes 27 ACE Inhibitors 28 Angiotensin Receptor Blockers 29 Diuretics 30 Beta-Blockers 31 Calcium Channel Blockers (Non-Dihydropyridine) 32 Calcium Channel Blockers (Dihydropyridine) 33 Vasodilators 34 Table of Contents iii

4 Cholesterol Management 37 Recommendations for Cholesterol Management in Patients with Diabetes 37 HMG-CoA Reductase Inhibitors statins 39 Statin Dose Limitations with HIV Drugs 40 Simvastatin Dose Limitations 41 Relative LDL-lowering Efficacy of Statin and Statin-based Therapies 42 Fibric Acid Derivatives fibrates 43 Absorption Inhibitor 43 Bile Acid Sequestrants 44 Nicotinic Acid 45 Omega-3 Fatty Acids 46 Proprotein Convertase Subtilisin Kexin type 9 (PCSK9) Inhibitors 47 Miscellaneous Topics 49 Common Agents for Obesity Management in Patients with Diabetes 49 Drug-Disease and Drug-Drug Interactions 51 Treatment of Hypoglycemic Emergency 57 Complementary and Alternative Medicine (CAM) Patient Use Guidelines 59 Commonly Used Complementary and Alternative Medicine (CAM) in Diabetes 60 References 65 Quick Guide to Medications iv

5 Introduction For the majority of people with diabetes, treatment to lower blood glucose requires pharmacologic intervention. Over 80% of people with type 2 diabetes require oral glucose-lowering medications, insulin, or both to reach glycemic goals. 1 In addition to oral medications, pharmacologic therapies for patients with diabetes often include other agents to treat the various associated co-morbid conditions or complications of diabetes. Healthcare professionals must be cognizant of the total range of therapies available for comprehensive diabetes care, not just those used to improve glycemic control. Educators should also be ready to advise patients about the effects of non-diabetes drug therapy on blood glucose levels, diabetes complications, and other aspects of self-management. Introduction v

6 Glucose-Lowering Agents 2,3,4 Drug (Brand name) Tolbutamide (Orinase, Generics) First-Generation Sulfonylureas* Stimulate insulin release Tolazamide (Tolinase, Generics) Chlorpropamide (Diabinese, Generics) Recommended dose 0.25 to 3 g divided doses 100 to 1000 mg in 1 2 divided doses 100 to 500 mg daily Maximum dose 2 to 3 g/day 750 to 1000 mg/day 500 mg/day Half-life, hours 5 to to 48 Onset, hours 1 4 to 6 1 Duration, hours 6 to to Metabolism Hepatic via CYP2C9 with active metabolites Hepatic with active metabolites Excretion Urine (75 85%), Feces Urine (85%), Feces Urine Precautions Adverse Events Comments Hepatic and kidney impairment may require a decreased dose Hypoglycemia, epigastric fullness, nausea, Disulfiram-like reaction, weight gain Divided doses may improve GI tolerance. Hepatic and kidney impairment may require a decreased dose Hypoglycemia, epigastric fullness, nausea, Disulfiram-like reaction, weight gain Doses >500 mg/day should be given in 2 divided doses. *First-generation sulfonylureas are rarely used due to the superior potency and side effect profile of second-generation agents. Hepatic via CYP2C9 with active metabolites Hepatic and kidney impairment may require a decreased dose Hypoglycemia, nausea, Disulfiramlike reaction, weight gain Longest duration of action of firstgeneration sulfonylureas. Glucose-Lowering Agents 3 Glycemic Control

7 Drug (Brand name) Webpage Recommended dose Glyburide (DiaBeta, Micronase, Glynase PresTabs, Generics) to 10 mg in 1 2 divided doses; 0.75 to 12 mg daily (Glynase) Second-Generation Sulfonylureas Stimulate insulin release Glipizide (Glucotrol /Glucotrol XL, Generics) to 20 mg in 1 2 divided doses; single dose for extended release (XL) Glimepiride (Amaryl, Generics) 1 to 4 mg daily Maximum dose 20 mg/day; 12 mg/day (Glynase) 40 mg/day; 20 mg/day (XL) 8 mg/day Half-life, hours Biphasic to ± 1.2 Onset, hours to 3 Duration, hours to Metabolism Hepatic to weakly active metabolites Hepatic via CYP2C9 to inactive metabolites Hepatic via CYP2C9 to M1 (active) and M2 (inactive) metabolites Excretion Feces (50%), Urine (50%) Urine (90%), Feces Urine (60%), Feces (40%) Precautions Hepatic and kidney impairment may require a decreased dose Hepatic and kidney impairment may require a decreased dose Hepatic and kidney impairment may require a decreased dose Adverse Events Hypoglycemia, weight gain Hypoglycemia, weight gain Hypoglycemia, weight gain Comments Administer once daily doses with breakfast or first main meal. Give doses >10 mg/day as 2 divided doses. Administer once daily doses 30 minutes before breakfast. Give doses >15 mg/day (non-xl) as 2 divided doses. Administer with breakfast or first main meal. Quick Guide to Medications 4 Glycemic Control

8 Drug (Brand name) Webpage Recommended dose Nonsulfonylurea-Secretagogues (Glinides) Stimulate insulin release Repaglinide (Prandin ) Nateglinide (Starlix ) Biguanides Inhibit hepatic glucose output Metformin (Glucophage, Generics) to 4.0 mg before meals 120 mg before meals 500 to 850 mg 3 times daily, or 1000 mg 2 times daily Maximum dose 16 mg/day 120 mg before meals 2550 mg/day 2000 mg/day Half-life, hours to 4.9 Metformin Extended Release (Glucophage XR ) to 2000 mg once daily with evening meal, or 1000 mg 2 times daily Onset, hours 0.25 to 0.5 Within 20 minutes Not related to dose Not related to dose Duration, hours 2 to 3 2 to 3 ~6 Up to 24 Metabolism Hepatic via CYP2C8 and CYP3A4 to inactive metabolites Hepatic via CYP2C9 and CYP3A4 Excretion Feces (~90%), Urine Urine (83%; ~16% unchanged), Feces Precautions Poor kidney and hepatic function Poor kidney and hepatic function N/A Urine (as unchanged drug) Renal impairment*, CHF, liver disease, alcohol abuse Adverse Events Hypoglycemia Hypoglycemia Diarrhea (self-limiting 7 10 days), lactic acidosis N/A Urine (as unchanged drug) Renal impairment*, CHF, liver disease, alcohol abuse Diarrhea (self-limiting 7 10 days), lactic acidosis Glucose-Lowering Agents 5 Glycemic Control

9 Drug (Brand name) Webpage Comments Nonsulfonylurea-Secretagogues (Glinides) Stimulate insulin release Repaglinide (Prandin ) Administer 15 to 30 minutes before each meal. Nateglinide (Starlix ) Administer 15 to 30 minutes before each meal. Biguanides Inhibit hepatic glucose output Metformin (Glucophage, Generics) Maximum effective dose is 2000 mg daily. Preferred initial agent for type 2 diabetes. Metformin Extended Release (Glucophage XR ) May have better GI tolerance compared to immediate release. *Metformin is contraindicated in male patients with a serum creatinine >1.5 mg/dl (female >1.4 mg/dl), and should be discontinued if egfr <30 ml/min. Quick Guide to Medications 6 Glycemic Control

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