Objectives 2/13/2013. Figuring out the dose. Sub Optimal Glycemic Control: Moving to the Appropriate Treatment

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1 Sub Optimal Glycemic Control: Moving to the Appropriate Treatment Judy Thomas, MSN, FNP-BC Holt and Walton, Rheumatology and Endocrinology Objectives Upon completion of this session you will be better able to: 1. Describe the various oral agents available for the management of type 2 diabetes and describe strategies for adjusting therapy to optimize patient outcomes. 2. Apply patient specific criteria for ongoing adjustments of the most effective treatment option for type 2 diabetes. 3. Select appropriate insulin formulations and regimens based on pharmacodynamic properties and patients lifestyle. 4. Intensify insulin therapy appropriately in patients with type 2 diabetes. 5. Communicate effectively with patients regarding their needs for insulin therapy, the appropriate use of insulin and blood glucose self-monitoring techniques. Figuring out the dose Depends on level of insulin resistance. Basal insulin should be approximately 40 to 50% of total daily dose, but this may vary from patient to patient How do you know that it is the right dose? No hypoglycemia occurs when patient is fasting 1

2 The Art Of Insulins Type Onset Peak Duration Timing with Meal Rapid Acting Insulins Humalog (Insulin lispro) Novolog (Insulin aspart) Short Acting Insulins (Regular) Humulin R Novolin R Intermediate Acting Insulins 5-15 minutes minutes minutes minutes 3-5 hours Administer 5-15 minutes before a meal 1-3 hours 3-5 hours Administer 5-10 minutes before a meal 1-5 hours 6-10 hours Administer 30 minutes prior to a meal Lente (Novolin L and Humulin L) 1-3 hours 6-14 hours hours Administer 15 minutes prior to meal if mixed with rapid acting insulin Administer 30 minutes prior to meal if mixed with RPH NPH (Novolin N and Humulin N) 1-2 hours 6-14 hours hours Administer 15 minutes prior to meal if mixed with rapid acting insulin Administer 30 minutes prior to meal if mixed with RPH Long-acting Insulins Lantus and Levemir 1 to 2 hrs 24 hrs Does not need to be given in regards to meals Insulin Secretion Adult human pancreas secretes units of insulin per day. Basal concentration in fasting state ~10 µu/ml 8-10 minutes after food ingestion, peripheral insulin begins to increase. At minutes after food ingestion, insulin concentration peaks. Plasma glucose returns to baseline by minutes. Plasma glucose levels below mg/dl do not stimulate insulin release. 2

3 Basal insulin Insulin Onset Peak Duration NPH 1-4 hrs 8-12 hrs hrs Ultralente 3-5 hrs hrs hrs Glargine(Lantus) and Levemir (Detemir) 1-4 hrs None In some pts, mild peak 24 hrs In some pts, may last only hrs Patients with renal insufficiency may have longer durations The Basal/Bolus Insulin Concept Basal Insulin Suppresses glucose production between meals and overnight Nearly constant levels 50 % of daily needs Bolus Insulin (mealtime or prandial) Limits hyperglycemia after meals Immediate rise and sharp peak at one hour 10% to 20% of total daily insulin requirement at each meal Physiologic Insulin Secretion: Basal/Bolus Concept Insulin (µu/ml) 50 Nutritional (Prandial) Insulin 25 0 Basal Insulin Breakfast Lunch Supper Suppresses Glucose Production Between Meals & Overnight Glucose (mg/dl) Nutritional Glucose 50 Basal Glucose A.M. P.M. Time of Day The 50/50 Rule 3

4 Which Insulins are Best for Nutritional Coverage? n Effect Insulin NPH Detemir (Levemir) Glargine (Lantus) Regular Lispro (Humalog) Aspart (Novolog) Glulisine (Apidra) Time (hours) Self-Monitoring of Blood Glucose (SMBG) THERAPEUTIC REGIMEN FREQUENCY Diet... periodically Oral agents x/day QD insulin injections x/day BID insulin injections x/day TID QID insulin or insulin pump x/day Can decrease to 2 3x per week if stable. Notes Results should be recorded in a log (with each column containing glucose values during the same time of day [e.g., fasting, pre supper, etc.]), so that trends can be tracked and acted upon at each visit. Most glucose meters have download capabilities that facilitate recording and displaying glucose values, usually both in log format as well as graphically 2011; Diabetes Facts and Guidelines: Silvio E. Inzucchi, M.D. Benefits are classified according to major effects on fasting glucose, postprandial glucose, and nonalcoholic fatty liver disease (NAFLD). Eight broad categories of risks are summarized. The intensity of the background shading of the cells reflects relative importance of the benefit or risk.* * The abbreviations used here correspond to those used on the algorithm (Fig. 1). ** The term glinide includes both repaglinide and nateglinide. Available at AACE December 2009 Update. May not be reproduced in any form without express written permission from AACE 4

5 LIFESTYLE MODIFICATION A1C > 9.0% AACE/ACE DIABETES ALGORITHM FOR GLYCEMIC CONTROL Drug Naive Under Treatment Symptoms No Symptoms MET + GLP-1 or DPP4 1 ± SU 7 TZD 2 GLP-1 or DPP4 1 ± TZD 2 1 DPP4 if PPG and FPG or GLP 1 if PPG 2 TZD if metabolic syndrome and/or nonalcoholic fatty liver disease (NAFLD) 6 a) Discontinue insulin secretagogue with multidose insulin b) Can use pramlintide with prandial insulin 7 Decrease secretagogue by 50% when added to GLP 1 or DPP 4 Available at AACE December 2009 Update. May not be reproduced in any form without express written permission from AACE LIFESTYLE MODIFICATION A1C % AACE/ACE DIABETES ALGORITHM FOR GLYCEMIC CONTROL Dual Therapy 8 MET + GLP-1 or DPP4 1 or TZD 2 SU or Glinide 4,5 2-3 Mos. *** Triple Therapy 9 *** If A1C goal not achieved safely GLP-1 + TZD 2 or DPP4 1 MET + GLP-1 or DPP4 1 + SU 7 TZD Mos. *** Preferred dinitial iti agent 1 DPP4 if PPG and FPG or GLP 1 if PPG 2 TZD if metabolic syndrome and/or nonalcoholic fatty liver disease (NAFLD) 4 Glinide if PPG or SU if FPG 5 Low dose secretagogue recommended 6 a) Discontinue insulin secretagogue with multidose insulin b) Can use pramlintide with prandial insulin 7 Decrease secretagogue by 50% when added to GLP 1 or DPP 4 8 If A1C <8.5%, combination Rx with agents that cause hypoglycemia should be used with caution 9 If A1C >8.5%, in patients on Dual Therapy, insulin should be considered Available at AACE December 2009 Update. May not be reproduced in any form without express written permission from AACE A1C % ** A1C % A1C > 9.0% Drug Naive Under Treatment Symptoms No Symptoms Monotherapy MET DPP4 1 GLP-1 TZD 2 AGI Mos. *** Dual Therapy GLP-1 ordpp4 1 MET + TZD 2 Glinide or SU 5 TZD + GLP-1 or DPP4 1 Colesevelam MET + AGI Mos. *** Triple Therapy TZD 2 MET + DPP4 1 GLP-1 or + Glinide or SU 4,7 2-3 Mos. *** Dual Therapy 8 GLP-1 or DPP4 1 MET or TZD + 2 SU or Glinide 4,5 2-3M Mos. *** Triple Therapy 9 GLP-1 or DPP4 1 + TZD 2 MET + GLP-1 or DPP4 1 + SU 7 TZD Mos. *** GLP-1 or DPP4 1 ± SU 7 MET + TZD 2 GLP-1 or DPP4 1 ± TZD 2 * May not be appropriate for all patients ** For patients with diabetes and A1C < 6.5%, pharmacologic Rx may be considered *** AACE/ACE Algorithm for Glycemic Control If A1C goal not achieved safely Committee Preferred initial agent Cochairpersons: 1 DPP4 if PPG and FPG or GLP 1 if PPG Helena W. Rodbard, MD, FACP, MACE 2 TZD if metabolic syndrome and/or Paul S. Jellinger, MD, MACE nonalcoholic fatty liver disease (NAFLD) Zachary T. Bloomgarden, MD, FACE 3 AGI if PPG Jaime A. Davidson, MD, FACP, MACE 4 Glinide if PPG or SU if FPG Daniel Einhorn, MD, FACP, FACE 5 Low dose secretagogue recommended Alan J. Garber, MD, PhD, FACE James R. Gavin III, MD, PhD 6 a) Discontinue insulin secretagogue George Grunberger, MD, FACP, FACE with multidose insulin Yehuda Handelsman, MD, FACP, FACE b) Can use pramlintide with prandial insulin Edward S. Horton, MD, FACE 7 Decrease secretagogue by 50% when added to GLP Harold Lebovitz, MD, FACE 1 or DPP 4 Philip Levy, MD, MACE 8 If A1C < 8.5%, combination Rx with agents that Etie S. Moghissi, MD, FACP, FACE cause hypoglycemia should be used with caution Stanley S. Schwartz, MD, FACE 9 If A1C > 8.5%, in patients on Dual Therapy, insulin should be considered Available at AACE December 2009 Update. May not be reproduced in any form without express written permission from AACE 5

6 Basal insulin Insulin Onset Peak Duration NPH 1-4 hrs 8-12 hrs hrs Ultralente 3-5 hrs hrs hrs Glargine(Lantus) and Levemir (Detemir) 1-4 hrs None In some pts, mild peak 24 hrs In some pts, may last only hrs Patients with renal insufficiency may have longer durations 6

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9 Maximum Oral Agents When combination therapy of 2-3 agents are used and patients has poor glycemic control may need insulin. Oral Agent Failure 1. Primary Failure: the patient is prescribed oral agents and their blood glucose not indicate lowered blood glucose after being on the medication for at least 3 months. 2. Secondary Failure: in type 2 patients, we frequently find that that a patient has a therapeutic response to the oral agents for years before secondary failure occurs. Summary of Oral Agents 1. No oral agents are used during pregnancy or breast feeding. 2. Children year old may use metformin. 3. Oral agents which cause weight gain; sulfonylureas, thiozolidiones and meglitinides. 4. Oral agents that may cause hypoglycemia; sulfonylureas, meglitinides. 5. Oral agents which do cause hypoglycemia if used as monotherapy; biguanide, thiozolidiones, alpha glucosidase inhibitors. 6. Previous surgeries may effect how medications are asborbed. 9

10 When A1C Doesn t Correlate to Blood Glucose Readings:Things to Remember About an A1C 1. A1C is not accurate in anemia of chronic disease such as ESRD. Or sample is hemolysed. 2. Consider when an A1C result is within the normal range and reading doesn t correlate, causes such as frequent low blood glucose readings or alcoholism with poor food intake could be the reason for the discrepency of the A1C and BG reading. 3. Consider when is the patient testing e.g. testing only fast or post prandially or immediately after exercising. 4. Consider if testing was done only post prandially. 5. Exam insulin injection technique, needle to short may be giving self injections intradermally, redness or bruising at site of injection indicates need to rotate injections within the site. Consider using use a fructosamine test (glycosylated serum albumin over 2-3 weeks) for more accurate correlation of long term control. 10