COPYRIGHT. Advancing to Insulin Replacement Therapy: When, Why, and How? Update in Internal Medicine December 5, Richard S.

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1 Advancing to Insulin Replacement Therapy: When, Why, and How? Update in Internal Medicine December 5, 2016 Richard S. Beaser, MD Medical Director, Professional Education Joslin Diabetes Center Associate Professor of Medicine Harvard Medical School

2 Key Messages Insulin Therapy Insulin is a highly effective diabetes treatment Individualize treatment goals and regimens Consider pathophysiology, self-care, and safety Use pattern assessment to adjust dosing and advance therapy To treat Type 2 Diabetes, consider the advancement sequence recommended by nationally-recognized guidelines from basal alone to basal-bolus insulin therapy Recognize and address patient, provider, and practice-level barriers to insulin therapy Some treatment services should be provided in the practice, others obtained by consultation

3 Aggressive Control of Diabetes: Goals of Treatment ADA AACE A1C (%) < Preprandial glucose (mg/dl) < hour postprandial glucose (mg/dl) < 180 < 140 A1C is gold standard measure of diabetes control over previous 2 3 months American Diabetes Association. Diabetes Care. 2016;39(suppl 1):S39-S46. Garber AJ, Abrahamson MA, Barzilay JI, et al. Endocrine Practice 2016;22:

4 Key Parameters Reflecting Glycemic Control A1C Preprandial glucose levels Fasting Sequentially through the day Postprandial glucose levels Absolute level Level relative to pre-prandial

5 Individualizing A1C Targets for People with T2DM Most 6.0% Intensive Less Intensive 7.0% Least Intensive 8.0% Low Moderate Few/Mild Risk from Hypoglycemia and other adverse drug effects High Disease Duration Newly Diagnosed Long-Standing Not usually modifiable Life Expectancy Long Absent Absent Few/Mild Short Important Comorbidities Severe Established Vascular Complications Severe Highly Motivated, Adherent, Excellent Self- Care Capacities Readily available Patient attitude/expected treatment effort Less motivated, Non-adherent, Poor Self-Care Capacities, Resources and Support System Limited Potentially modifiable ADA, EASD Position Statement. Diabetes Care 2015;38;

6 Physiologic Insulin Secretion: 24-hour Profile Insulin (µu/ml) Glucose (mg/dl) Basal insulin Breakfast Lunch Dinner AM PM Time of day Basal glucose

7 Relative Contribution of FPG and PPG to Overall Hyperglycemia Depending on A1C Quintiles Contribution (%) Postprandial glucose Fasting glucose 0 < >10.2 n=58 n=58 n=58 n=58 n=58 A1C (%) Quintiles Monnier L et al. Diabetes Care. 2003;26:

8 When to Consider Insulin in a person with Type 2 Diabetes When a combination of non-insulin antidiabetes medications are unable to achieve A1C target High fasting or postprandial glycemia Unacceptable side effects of other medications Advanced hepatic or renal disease Special considerations (steroids, infection, pregnancy) Hyperglycemia in a hospitalized patient Severely uncontrolled diabetes* * Random Glucose > 300 mg/dl, A1C > 10%, Ketonuria, Symptomatic polyuria/polydipsia, weight loss Nathan DM, et al. Diabetes Care. 2009; volume 32, Inzucchi SE, et al. Diabetes Care. 2012;35(6): ADA Diabetes Care. 2015:38(Suppl 1):S41-S48.

9 Type 2 Diabetes and Need for Insulin UKPDS: at 6 years, more than 50% of patients (newly diagnosed at start of study) need insulin to reach target (FPG 6.0 mmol/l) Patients Requiring Insulin (%) Years from Randomization FPG = fasting plasma glucose Wright A, et al. Diabetes Care. 2002;25:

10 Types of Insulin Rapid-acting: - Inhaled human insulin Rapid-acting analogs: - Aspart, Glulisine, Lispro (U-100 or U-200) Short-acting insulin: Regular (soluble) Intermediate-acting insulin: NPH Human insulin 70/30: - Premix NPH/regular Premixed Analogs: - Insulin lispro mix 75/25, 50/50 - Biphasic insulin aspart 70/ Time (hours) Adapted from Hirsch I. N Engl J Med. 2005;352: Long-acting insulin: - Detemir, Glargine - Glargine U Degludec U-100 or U-200

11 Insulin to provide Basal and Bolus Coverage Basal insulin Replicates normal basal insulin secretion in the fasting and postabsorptive state which regulates hepatic glucose production and limits lipolysis Controls fasting and premeal glucose levels A good basal insulin should have a low risk of hypoglycemia Bolus insulin Replicates acute insulin secretion at mealtimes to both suppress liver glucose production and increase uptake of glucose in peripheral tissues Blunts rise in glucose after meals

12 TDD = Total Daily Dose Reprinted with permission from American Association of Clinical Endocrinologists 2016 AACE. Garber, AJ Abrahamson MJ, Barzilay JI, et al. AACE/ACE comprehensive type 2 diabetes management algorithm Endocr Pract. 2016;22:

13 Desired Characteristics of Replacement Basal Insulin Mimics natural pancreatic basal insulin secretory pattern No distinct peak effect Continued effect over 24 hours Minimizes risk of nocturnal hypoglycemia Administered once daily for optimal patient adherence Reliable absorption pattern

14 Weight Gain with Detemir vs NPH A1C (%) *P< Detemir NPH Weeks +6.2 lb +2.6 lb* At least 70% of subjects in each group achieved A1C 7% Average Body Weight (lb) Hermansen K et al. Diabetes Care. 2006;29:

15 Glargine vs NPH in Treat-To-Target No Difference in A1C but Reduced Hypoglycemia with Glargine A1C 9.0% 8.5% 8.0% 7.5% 7.0% 6.5% 6.0% 756 Patients with Type 2 Diabetes on 1 or 2 Oral Agents Glycemic Control Over Time Glargine NPH Weeks of Treatment Cumulative Number of Events (Documented PG 56 mg/dl) Hypoglycemia Hypoglycemia Reduced 42-46% Time (days) PG = plasma glucose Adapted from Riddle et al. Diabetes Care. 2003;26:

16 Treat-to-Target Trial: Timing and Frequency of Hypoglycemia Hypoglycemia by Time of Day Hypoglycemia Episodes (PG 72 mg/dl) Basal insulin * * * * Insulin glargine NPH insulin B L D * * * 20:00 22:00 24:00 2:00 4:00 6:00 8:00 10:00 12:00 14:00 16:00 18:00 20:00 * P <0.05 (between treatment). PG = plasma-referenced glucose. Time Riddle MC, et al. Diabetes Care. 2003;26:

17 Pharmacodynamics of Glargine U-300 versus U-100 GIR (mg/kg -1 min -1 )* SC Injection Time (hours) U U/kg -1 U U/kg -1 The U-300 glargine has a flatter more prolonged effect The time it takes for 50% of the effect of a single injection U-100 = 12.1 hours U-300 = 16.7 hours U U/kg -1 U U/kg -1 GIR = glucose infusion rate. Shiramoto M et al. Diab Obes Metab. 2015;17:

18 U-300 Insulin Glargine U-300 insulin glargine offers a smaller depot surface area leading to a reduced rate of absorption Provides a flatter and prolonged pharmacokinetic and pharmacodynamic profiles and more consistency Half-life is ~23 hours Associated with less hypoglycemia especially nocturnal hypoglycemia Only available in pens 300 U/mL, 1.5 ml Max dose per shot is 80 units with current pen Garber AJ. Diabetes Obesity Metab 2014;16: Owens DR, et al. Diabetes Metab Res Rev. 2014;30(2): Steinstraesser A, et al. Diabetes Obes Metab. 2014;16: Accessed September 4, 2015

19 Comparison of Glargine U-300 to Glargine U-100 Similar reduction in A1C & FPG Less nocturnal hypoglycemia Likely need 15% higher dose Ritzel R, et al. Diabetes, Obesity and Metabolism 2015;17:

20 Pharmacodynamics of Degludec Glucose Lowering Effect on Day 6 (mg/kg/min) Ideg 0.8 U/kg Ideg 0.6 U/kg Ideg 0.4 U/kg Time since Injection (hours) desb30 insulin acylated (16-c fatty acid chain) at LysB29 Half-life is ~25.4 hours, duration > 42 h Josse RG and Woo V. Diabetes Obes Metab. 2013;15(12): Garber AJ. Diabetes Obesity Metab 2014; 16: Heise et al. Diabetes Obes Metab 2012;14:944 50

21 Variability of Effect Variability in effects of an insulin can cause unexplainable variations in glucose control from day to day Insulin Within Subject Variability (CV% of AUC GIR) NPH 68 Glargine U Detemir 27 Glargine U Degludec 20 Adapted from: Rossetti P, et al. Diabetes Obes Metab, 2014;16: ; Becker RHA, et al. Diabetes Obes Metab, 2015;17:261-7

22 Insulin Titration: Options when control is not adequate using one daily injection of basal insulin Basal plus GLP-1 agonist OR Switch to a premixed insulin analog Divide dose in half and give twice daily (before breakfast and dinner) OR Basal Plus Basal insulin plus a short-acting insulin analogue before the largest meal of the day OR Switch to basal-bolus regimen 23

23 Exenatide BID Added to Insulin Glargine Outcome PBO EXENATIDE BID P- Value Δ FPG (mg/dl) a Δ Insulin dose (U/d) b Δ Weight (kg) <.001 Hypoglycemia c (events/patient-y) Discontinuation due to AEs (% of patients) <.01 a Baseline FPG: 149 and 142 mg/dl for PBO and EXN BID groups, respectively. b Baseline insulin: 47.4 and 49.5 U/d for PBO and EXN BID groups, respectively. c 1 reported event of major hypoglycemia (PBO group). EXN BID or PBO Added to GLAR 30-week trial (N = 259) A1C Change (%) GLAR + EXN BID P < GLAR + PBO Adapted from Buse JB et al. Ann Intern Med. 2011;154:

24 Comparison of GLP-1 RA s vs. Prandial Insulin when used with Basal Insulin A1C, % LIRAGLUTIDE QD 1, a P =.0024 ASPART QD 1, a Noninferior EXENATIDE BID 2, b LISPRO TID Outcome: LIRA vs. ASPART 1 EXEN BID vs. LISPRO 2 ALBIG vs. LISPRO 3 Δ Weight, kg 2.8* * 0.7* 0.8 Hypoglycemia d 1.0* Nausea, % LIRA > ASP, first 2 wks Basal Insulin used Degludec Glargine Glargine Duration / n 26 weeks / weeks / weeks / 566 2,3, b, c Noninferior ALBIGLUTIDE QW 3, c a Added to DEG (26 wk; N = 177) b Added to GLAR (30 wk; N = 637). c Added to GLAR (26 wk; N = 566). d Rates of severe hypoglycemia were low across groups * P < Mathieu et al. Diabetes Obes Metab. 2014;16: Diamant et al. Diabetes Care. 2014;37: Rosenstock et al. Diabetes Care. 2014;37: Eli Lilly and Co. Trulicity (dulaglutide) prescribing information US FDA. Drugs@FDA.

25 Adding GLP-1-RA vs. bolus insulin to optimized basal insulin Rx program for Type 2 diabetes Diamant M et al Diabetes Care 2014;37:

26 Combination Basal Insulin GLP-1 RA Fixed Ratio Formulations DEG-LIRA 1,a,b DEG 1,b LIRA 1,b GLAR-LIXI 2,a,c GLAR 2,c Δ A1C, % Δ BW, KG A1C < 7%, %: d 65 d Noninferior to DEG; Superior to LIRA d 0.5 e -3.0 d d Superior to GLAR Ø 3 severe hypoglycemic episodes per group Ø Lower rate of hypoglycemia for LIRA vs DEG or DEG-LIRA (overall and nocturnal) 1 Ø Lower rate of hypoglycemia for GLAR-LIXI than for GLAR (overall) 2,e Current GLP-1 RAs should not be mixed with or injected adjacent to insulin 3 DEG=Degludec; Lira=liraglutide GLAR=Glargine Lixi=Lixisenatide 1. Gough et al. Lancet Diabetes Endocrinol. 2014;2: Rosenstock et al. Diabetologia. 2014;57(suppl 1) [abstract 241]. 3. US FDA. Drugs@FDA. DA. a Not US FDA approved. b 26-week open-label, treat-to-target RCT; N = 1663 (insulin naïve). c 24-week open-label, treat-to-target RCT; N = 323 (insulin naïve). d P <.001 vs DEG-LIRA; e P <.001 vs GLAR-LIXI.

27 Role for Premixed Insulin Advantages Easy (no mixing, single product, pens avail.) Covers insulin requirements through most of day Disadvantages Not physiologic Less Flexible: requires consistent meal/exercise pattern, and cannot titrate individual insulins unless custom mixed insulin is used Nocturnal hypoglycemia (presupper NPH) Fasting hyperglycemia (presupper NPH wears off) Higher A1C (realistic goal of 8%) Janka HU et al. Diabetes Care. 2005;28: Fritsche et al. Diab Obes Metab. 2010;12(2): ADA, EASD Position Statement. Diabetes Care 2012;35;

28 The Study: Achievement of HbA1c Targets With Premixed Insulin Analog Therapy Subjects (Cumulative %) ITT population* (n = 100) Mean baseline A1C level: 8.6% % (AACE) <7.0% (ADA) 77 QD BID TID *All patients enrolled in the trial. Garber AJ, et al. Diabetes Obes Metab. 2006;8(1):

29 INITIATE: Basal Analog vs Premixed Analog A1C Level (%) Change in A1C Level From Baseline to Study End Baseline Endpoint 9.8% 7.4% Insulin Glargine + OADs P < % 2.8% 9.7% Raskin P, Allen E, Hollander P, et al. Diabetes Care. 2005;28(2): % Biphasic Insulin Aspart 70/30 Episodes per Patient Year Documented Hypoglycemic Episodes (<56 mg/dl) 0.7 Insulin Glargine + OADs P < Biphasic Insulin Aspart 70/30 Total units = with glargine plus OADs vs with premixed insulin OAD = Oral antihypertlycemic agent 30

30 Rate of Hypoglycemic Event Occurrence Description of Event (Adjusted Rate) SMBG < 70 mg/dl (with symptoms) SMBG < 50 mg/dl (with symptoms) Insulin Glargine/ Insulin Glulisine-3 (Events/Patient- Year; n=194) Insulin Glargine/ Insulin Glulisine-1 (Events/Patient- Year; n=194) Premixed Insulin Aspart 70/30 (Events/Patient- Year; n=194) 7.23 (0.99) a 7.11 (0.99) a (1.68) 0.89 (0.15) b 0.83 (0.15) b 1.91 (0.31) SMBG < 36 mg/dl 0.15 (0.03) 0.10 (0.03) a 0.23 (0.05) Severe hypoglycemia c 0.17 (0.05) 0.10 (0.03) 0.17 (0.05) Serious hypoglycemia d N/A N/A N/A Insulin glargine/insulin glulisine-3 and insulin glargine/insulin glulisine-1 groups had lower hypoglycemic event rates than premixed insulin aspart 70/30 group a P<0.01 vs premixed insulin aspart 70/30 b P vs premixed insulin aspart 70/30 c Hypoglycemic events requiring assistance and either BG <36 mg/dl or prompt response to countermeasures d Hypoglycemia with coma/loss of consciousness or seizure/convulsion. N/A = not applicable; SMBG = self-monitored blood glucose. Riddle et al. ADA Scientific Sessions

31 Comparison of Insulin Degludec/Insulin Aspart and Biphasic Insulin Aspart 30 in Uncontrolled, Insulin-Treated Type 2 Diabetes Fulcher, GR, et al. Diabetes Care 2014:37:

32 Clinical Features of Rapid-Acting Analogues: Aspart, Glulisine, and Lispro Administration immediately prior to meals Faster onset of action matches timing of carbohydrate absorption Limits postprandial hyperglycemic peaks Shorter duration of activity Reduced risk of late postprandial hypoglycemia Frequently can have late postprandial hyperglycemia Glulisine can be given after meals if needed * * Garg S et al. American Diabetes Association 64 th Scientific Sessions; June 4-8, 2004; Orlando, FL; Abstract 530-P

33 Fewer Nocturnal Hypoglycemic Events in Patients Treated with Aspart vs Regular Human Insulin Major Nocturnal Hypoglycemic Events per Patient-Year % Aspart P= Regular Human Insulin Adapted from Heller SR et al. Diabet Med. 2004;21:

34 Concentrated Insulin Lispro U-200 vs U-100 Pharmacodynamics of Lispro U-100 & U-200 are comparable Glucose Infusion Rate (mg/min) Insulin Lispro 100 Units/ml Insulin Lispro 200 Units/ml Time From Dose (h) (Mean SE Data) de la Peña A et al. Clin Pharmacol Drug Dev 2016;5:69-75

35 Inhaled Insulin Technosphere insulin (TI) marketed as Afrezza, recently FDA approved Indicated for adults with type 1 or 2 diabetes, in combination with longacting insulin. Ultra-rapid-acting insulin: Onset minutes, peak 60 minutes, duration hr RSS = Rapid-acting analog GIR = Glucose infusion rate Afrezza Package insert; Santos Cavaiola T, Edelman S. Clin Ther. 2014;36:

36 Inhaled Insulin: Limitations and Contraindications Limitations: Inhaled insulin is not a substitute for long-acting insulin. Not recommended for the treatment of diabetic ketoacidosis Not recommended in patients who smoke or who have stopped smoking in last 6 months. Contraindications: During episodes of hypoglycemia In patients who have chronic lung disease such as COPD or asthma inologicandmetabolicdrugsadvisorycommittee/ucm pdf

37 Adding Bolus Insulin Consider adding prandial (mealtime) insulin in about 3 6 months if: A1C is elevated Significant postprandial glucose excursions occur (> 180 mg/dl) There are significant drops in glucose between meals or overnight as the basal insulin dose is increased Likely needed if the total daily insulin dose exceeds 0.5 Units/kg/day. ADA, EASD Position Statement. Diabetes Care 2015;38;

38 Adding Bolus Insulin Add prandial insulin before meal with largest glucose excursion (>180 mg/dl) or the meal with the largest CHO content. Other meals can be covered subsequently. Alternatively start with coverage of all three meals at once. TDD: U/kg; 50/50 basal/prandial Antihyperglycemic medications: Generally, stop insulin secretagogues (SU, DPP-4 inhibitors, glinides) Reduce or stop TZD s Based on: Nathan DM, et al. Diabetes Care. 2009;32: ADA, EASD Position Statement. Diabetes Care 2015;38; AACE/ACE Comprehensive Diabetes Management Algorithm, Endocr Pract. 2015;21(No. 4) TDD=Total daily dose SU = Sulfonlyurea

39 STEPwise Study Do you add injection at the largest meal or the one with the highest postprandial elevation? Overall reduction in HbA1C of 1.2% was achieved with the addition of prandial insulin. Greatest HbA1C reductions were achieved with the first and second bolus injections. Glycemic improvement comparable in both groups. Number of hypoglycemic episodes increased with increasing number of prandial injections. Basal-bolus treatment can be introduced in a more patient-friendly approach, using simple stepwise addition of prandial insulin. Meneghini, et al. Endocr Pract. 2011;17:

40 Adding Prandial Insulin to Basal Therapy Further Improves HbA1C Decrease in A1C (%) Glargine ± OHA (n=534) * Glargine ± OHA + OD Prandial (n=534) Glargine ± OHA + BD Prandial (n=178) Glargine ± OHA + > BD Prandial (n=193) * * * * p<0.001 for baseline to endpoint change: OHA = oral antihyperglycemic agent; OD=once daily; BD=twice daily Davies M et al Diabetes Obes Metab May;10(5):

41 Physiologic Insulin Regimens with basal insulin plus rapid-acting insulin dosing before each meal Checking blood glucose 4 to 6 times a day CHO counting or consistent CHO Intake Premeal insulin dosing by algorithmic scale or, preferably, carbohydrate counting Surveillance and risk for hypoglycemia Record keeping: Monitoring rather than just checking

42 Sample Insulin Adjustment Algorithm: Premeal Rapid-Acting and Bedtime Basal Insulin An option for determining premeal insulin doses if carbohydrate counting is not possible Rapid-Acting Insulin BLOOD GLUCOSE BREAKFAST LUNCH SUPPER BED 0 70* OVER *Treat with food first, retest, then use algorithmic dose. Basal Insulin 20 *Treat with food first, retest, then use algorithmic dose.

43 Carbohydrate Counting, Matching and Postprandial Control Two factors primarily govern the dose of premeal insulin: Grams of carbohydrate Correction doses if premeal hyperglycemia is present Two calculations are useful for initial dosing: Carbohydrate coverage: Total daily insulin dose (TDD) divided into 500 gives the approximate number of carb grams that 1 unit of rapid acting insulin will cover. Correction dose: Divide the TDD into Usually initially target a glucose of 120 mg/dl

44 Carbohydrate Counting, Matching and Postprandial Control: Example Ø Calculating a carbohydrate (CHO) counting insulin dosing program for a total daily insulin dose of 50 units: Basal insulin: 25 units daily at bedtime Premeal coverage based on CHO intake: Total daily insulin dose (TDD) = 50 units 500/50 = 10 Give 1 unit of premeal rapid-acting insulin for every 10 grams of carbohydrate to be consumed. Correction dose: 1500/50 = 30 Give an extra unit of rapid-acting premeal insulin for every 30 points above 120 mg/dl

45 Simple Algorithm vs Carbohydrate Counting For Mealtime Insulin Adjustment A1C % Insulin dose (U/kg/d) Simple Algorithm: 1.9 Carb Counting: 1.7 P < Baseline Simple Algorithm Group Carb-Count Group Weight gain (kg): Simple Algorithm: 3.6 Carb Counting: 2.4 P = 0.06 Bergenstal R, Johnson M, Powers MA et al. Diabetes Care. 2008;31:

46 Glucose Monitoring No one should perform a single glucose test unless he or she knows what to do with the result! There is a difference between glucose checking (testing) and glucose monitoring Individualize monitoring schedule Record-keeping is of crucial importance to the monitoring process

47 External Insulin Pump Using Rapid Acting Insulin Insulin Effect Insulin Bolus Doses B L S Snack HS B Meals Insulin Basal

48 Suggested Sequence for Assessment of Glycemic Patterns Fasting value General premeal and bedtime values and trends throughout the day Postprandial values absolute levels Relative change, pre- to postprandial glycemic levels à Also, continually monitor nocturnal glycemia

49 Continuous Glucose Monitoring Provides a More Comprehensive Picture of the Patterns Glucose (mg/dl) Fingerstick Blood Glucoses (Type 1) Glucose measurement Insulin bolus Target Range 0 12:00 am 6:00 am 12:00 6:00 pm 12:00 am

50 CGM Software Report

51 Factors Influencing Therapeutic Choices Ø Medical needs and treatment goals A1C level and distance from target Postprandial glycemia Ø Safety Ø Need for flexibility in treatment program Ø Patient issues with respect to insulin use Intellect and judgment Psychosocial and cultural considerations Physical capabilities and limitations Other medical conditions and issues relating to use of other non-insulin medications

52 Patient Barriers to Insulin Initiation Ø Needing insulin represents a personal failure Describe the natural progression of type 2 diabetes and the inevitability of the need for insulin Do not use insulin as a threat Ø Insulin is not effective Many patients do not believe insulin is effective Match insulin use to goals that patients can see: Glycemic patterns, symptoms Ø Insulin causes complications Many patients saw relatives/friends start insulin in the context of bad events happening Provide supportive education Ø Impact on lifestyle Perceived causes: Injection schedule, hypoglycemia Provide supportive education Insulin pens Adapted from Funnell MM. Clinical Diabetes. 2007;25(1):36-38.

53 Patient Barriers to Insulin Initiation Ø Injections are painful Perceive that they are the same as inoculations or other painful injection experiences Compare to glucose checking Demonstration injection Discuss needle size; use of pens Ø Fear of hypoglycemia Observing problems in others Education focusing on advantages of newer insulins, hypoglycemia avoidance, appropriate goal setting Ø Insulin causes weight gain Acknowledge the possibility Discuss strategies to avoid: Dietitian, CHO counting Ø Cost Acknowledge/compare cost for insulin vs. DM Meds Explore strategies to reduce costs Adapted from Funnell MM. Clinical Diabetes. 2007;25(1):36-38.

54 Physician Barriers to Insulin Initiation Ø Systems deficiencies Recognizing indications, impact of treatment: EMR reminders Educational support: Train office staff; identify/develop working relationship with additional educational resources Ø Provider education about insulin Optimize your own knowledge and skills Ø Concern about hypoglycemia Similar issues to patients Set individualized goals and design appropriate Rx Provide supportive education Ø Weight gain Use dietitians, physiologic insulin programs Ø Unease in dealing with patient emotions/barriers Develop strategies and practice them! Adapted from Funnell MM. Clinical Diabetes. 2007;25(1): Derr RL, et al. Diabetes Spectrum. 2007; 20(3):

55 A Stepwise Perspective on Insulin Treatment Ability to identify people for whom insulin is indicated and discuss this need with them Capability or identified referral resources to oversee insulin treatment initiation and support Ability to teach insulin use: Techniques Knowledge and Skills for self-management Spectrum of programs, from basal to pumps Ability to identify people for whom the current program is inadequate and advancement of therapy is indicated Troubleshooting Referral management

56 A Stepwise Perspective on Insulin Treatment Ability to identify people for whom insulin is indicated and discuss this need with them Capability or identified referral resources to oversee insulin treatment initiation and support Ability to teach insulin use: Techniques Knowledge and Skills for self-management Spectrum of programs, from basal to pumps Ability to identify people for whom the current program is inadequate and advancement of therapy is indicated Troubleshooting Referral management

57 Take-Away Messages Treatment goals, program design, and monitoring recommendations must be individualized Monitoring of glycemic patterns is a key tool to guide therapeutic decisions Basal-bolus regimens require more injections but provide better insulin coverage and glycemic control Patient, provider, and practice systems barriers to insulin therapy must be recognized and addressed Self-assess office capabilities in the context of insulin treatment support

58 Insulin is a remedy for the wise and not the foolish, be they patients or doctors. Everyone knows it requires brains to live long with diabetes, but to use insulin successfully requires more brains. Elliott P. Joslin, MD, ScD Diabetic Manual, 1959