Emerging Challenges in Primary Care: Insulin Management of Type 2 Diabetes: Designing Treatments and Overcoming Barriers

Transcription

1 Emerging Challenges in Primary Care: 2016 Insulin Management of Type 2 Diabetes: Designing Treatments and Overcoming Barriers

2 Faculty Richard S. Beaser, MD Senior Staff Physician Chair, Continuing Medical Education Committee Joslin Diabetes Center Associate Clinical Professor of Medicine Harvard Medical School Boston, MA Mark Stolar, MD Associate Professor of Clinical Medicine Feinberg School of Medicine Northwestern University Chicago, IL Robert S. Busch, MD, FACE Director of Clinical Research Albany Medical Faculty: Community Endocrine Group Albany, NY 2

3 Disclosures Richard S. Beaser, MD has no relationships to disclose. Robert S. Busch, MD, FACE serves as a speaker for Astra Zeneca, Eli Lilly, Boehringer Ingelheim and Novo Nordisk. Mark Stolar, MD serves as a speaker for and/or on the advisory board for Takeda, Sanofi, and Astra Zeneca. 3

4 Learning Objectives Summarize the natural progression of type 2 diabetes and how that is reflected in signs such as the glycemic monitoring patterns and other key clinical manifestations Describe the current and newer insulins, and how they may be utilized in the design of an insulin replacement program Provide educational support for individualized insulin regimens to achieve targeted levels of glycemic control for people with diabetes List common obstacles to insulin initiation, treatment, and adherence stemming from patient, provider, and officesystems based issues, and methods to address them 4

5 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 Consider basal-bolus insulin therapy when conventional insulin programs are ineffective Recognize and address patient, provider, and practicelevel barriers to insulin therapy Some treatment services should be provided in the practice, others obtained by consultation 5

6 Insulin Management Case 1: Roger 6

7 Roger: Introduction 47 yo man with 10 years of T2DM who comes for diabetes treatment Significant past history includes: Dyslipidemia & Hypertension, well treated Type 2 diabetes Ø Lifestyle Rx X 4 years Ø Metformin, the glyburide added over the next 3 years Ø Pioglitazone added 3 years ago Ø DPP-4 inhibitor replace glyburide 2 years ago Ø SGLT2 inhibitor added 10 months ago Ø Unaware of any complications With most changes, achieved A1C in the mid 7 s for a while, but then it drifted back into the 8 s 7

8 More on Roger Ø Family history: Mother: 74, with type 2 diabetes, dyslipidemia Father: Died at 71, DM, CAD, PVD Son age 22 in graduate school Daughters age 19 (College) and 17 (High School) Ø Social Hx Work: Manager of a large store in a mall No regular exercise program, but active at work Does not smoke Rare alcohol ingestion 8

9 Roger: Further information Ø Doesn t want insulin An associate at work uses insulin and has frequent hypoglycemia during work hours Father started insulin and died soon after Ø Other issues: Job security Concerned about finances/college tuitions Struggles with nutrition/activity multiple sessions with CDE s to help with these issues 9

10 Roger Ø Current antidiabetes medications: Metformin ER 1000 mg BID Pioglitazone 30 mg QD DPP-4 inhibitor An SGLT-2 inhibitor Ø Physical Examination 5 11", 218 lbs, BMI = 30.5 BP = 138/82 Physical examination otherwise unremarkable Ø Current A1C: 8.1% 10

11 SMBG Results: What would you do? Breakfast Post- Brkfst Lunch Post- Lunch Supper Sunday Post- Supper Bedtime Monday Tuesday 154 Wednesday Thursday Friday Saturday Increase the dose of Pioglitazone and add one more medication 2. Refer to an educator for general review and to discuss injections 3. Change the DPP-4i to a GLP-1 RA 4. Start basal insulin 5. Add fixed mixture insulin BID Metformin ER 1000 mg BID; Pioglitazone 30 mg QD ; DPP-4 inhibitor; SGLT2 inhibitor A1C: 8.1% 11

12 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 12

13 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):

14 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):

15 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):

16 Roger What actually happened Ø Ø Ø Ø Ø Saw educator who addressed barriers Work associate s hypoglycemia issues Father starting insulin and passing away shortly after Job security and finances Struggles with nutrition Other Session with a dietitian Started on basal insulin, initially 12 units at bedtime, and titrated upward Pioglitazone stopped, other meds continued Monitoring plan: Check 3 times/ day, vary checking systematically pre & post prandial 16

17 Aggressive Control of Diabetes: Goals of Treatment ADA AACE A1C (%) < Preprandial glucose (mg/ dl) 2-hour postprandial glucose (mg/dl) < 110 < 180 < 140 A1C is gold standard measure of diabetes control over previous 2 3 months American Diabetes Association. Diabetes Care. 2014;37(suppl 1):S14-S80. Handelsman Y, Mechanick JI, Blonde L et al. Endocrine Practice. 2011;17(Suppl 2):

18 Individualizing A1C Targets for People with T2DM Most 6.0% Intensive Less Intensive 7.0% Least Intensive 8.0% Highly Motivated, Adherent, Knowledgeable, Excellent Self-Care Capacities, & Comprehensive Support Systems Low Moderate Psychosocioeconomic Considerations Less motivated, Non-adherent, Limited Insight, Poor Self-Care Capacities, & Weak Support Systems Hypoglycemia Risk High Patient Age Disease Duration Other Comorbidities None Few/Mild Multiple/Severe None None Established Vascular Complications Cardiovascular Disease Early Micro Advanced Micro Data from Ismail-Beigi F, et al. Ann Intern Med. 2011;154(8): , also published in ADA Standards of Care 2015 Diabetes Care 2015;38(Suppl 1)

19 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 (%) FPG = fasting plasma glucose Years from Randomization Wright A, et al. Diabetes Care. 2002;25:

20 Natural History of Type 2 Diabetes Severity of Glucose Intolerance NGT IGT Frank Diabetes Insulin Resistance Insulin Secretion Postprandial Glucose Fasting Blood Glucose Worsens with Time Risk of Microvascular Complications Risk of Macrovascular Complications Normal Blood Glucose Years to Decades Typical Diagnosis of Diabetes 20

21 Relative Contribution of FPG and PPG to Overall Hyperglycemia Depending on A1C Quintiles 100 Postprandial glucose Fasting glucose Contribution, % < >10.2 n=58 n=58 n=58 n=58 n=58 A1C (%) Quintiles 21 Monnier L et al. Diabetes Care. 2003;26: Monnier L et al. Diabetes Care 2003;26:

22 Key Parameters Reflecting Glycemic Control A1C Preprandial glucose levels Fasting Sequentially through the day Postprandial glucose levels Absolute level Level relative to pre-prandial 22

23 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. 23

24 Insulin in Newly Diagnosed T2DM Percentage of Patients in Remission CSII (N=137) MDI (N=124) OHA (N=121) Treatment was stopped after normoglycemia was maintained for 2 weeks 51% 45% 27% P = Days in Remission Target glycemic control was achieved in less time (4 & 5.6 days) and in more CSII and MDI pts (97.1% & 95.2%) than OHA pts (9.3 days and 83.5%) Weng J, et al. Lancet. 2008;371: CSII = continuous subcutaneous insulin infusion MDI = multiple daily insulin injections OHA = oral hypoglycemic agents 24

25 Current Limitations of Insulin Delivery Lack of closed feedback loop to control dosing Requirement for parenteral administration, or, more recently, inhaled insulin Lack of portal administration Poor reproducibility, site-to-site and day-to-day Limitations in true basal or true bolus kinetics Empiric therapy adjusted for each patient Need for multiple injections/doses or continuous infusion for very good to excellent glycemic control 25

26 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 26

27 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 27

28 Weight Gain with Detemir vs NPH A1C (%) Detemir NPH +6.2 lb +2.6 lb* Average Body Weight (lb) Weeks At least 70% of subjects in each group achieved A1C 7% *P<.001 Hermansen K et al. Diabetes Care. 2006;29:

29 Glargine vs NPH in Treat-To-Target No Difference in A1C but Reduced Hypoglycemia with Glargine A1c Level (%) NPH Glargine Treatment Duration (weeks) Cumulative Number of Events Documented Glucose 56 mg/dl ) Hypoglycemia Reduced 42-46% NPH Glargine Time (days) Adapted from Riddle M, et al. Diabetes Care. 2003;26:

30 Variability in Daily Glucose Values for People Using Insulin Therapy Food quantity Food types (glycemic index) Activity Stress psychological and physical Hypoglycemia and rebound GI absorption rate Insulin absorption rate and other factors that cause daily differences in insulin action 30

31 Pharmacodynamic Profiles of Currently-Available Basal Insulin Analogs Glargine Detemir GIR (mg/kg/min) U/kg T1D 0.35 U/kg T1D 0.4 U/kg T1D 0.5 U/kg T2D 0.8 U/kg T2D GIR (mg/kg/min) U/kg T1D 0.4 U/kg T1D 0.4 U/kg T2D 0.8 U/kg T2D Time (hours) Time (hours) Glucose Infusion Rates (GIR) after Basal Insulin Injection T1D = type 1 diabetes; T2D = type 2 diabetes. Garber AJ, Diabetes Obesity Metab. 2014;16:

32 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 Owens DR, et al. Diabetes Metab Res Rev. 2014;30(2): Steinstraesser A, et al. Diabetes Obes Metab. 2014;16: hjp:// Accessed September 4,

33 Pharmacodynamics of U300 Glargine vs. U100 Glargine GIR (mg/kg -1 min -1 )* SC Injection U U/kg -1 U U/kg U U/kg -1 U U/kg -1 Time (hours) 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 GIR = glucose infusion rate. Tillner J, et al. Poster 920P 73 rd ADA Scientific Sessions June 21-25, 2013, Chicago, IL. Accessed September 4,

34 U-300 Insulin Glargine vs U-100 Insulin Glargine in T2DM Cumulative Number of Confirmed or Severe Hypoglycemic Events/Participant Hypoglycemia GLAR-100 GLAR Time, weeks Mean Weight Change, kg Weight Change GLAR-100 GLAR-300 P =.015 Equivalent A1C reduction for U-300 glargine and U-100 glargine 28-week, open-label, treat-to-target, RCT; N = 818; BL weight, 98.0 kg to 98.7 kg; mean BMI = 34.8 kg/m 2 ; hypoglycemia defined in accordance with ADA criteria (assistance needed or confirmed BG 70 mg/dl). Yki-Jarvinen H, et al. Diabetes Care. 2014;37:

35 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 desb30 insulin acylated (16-c fatty acid chain) at LysB29 Half-life is ~25.4 hours, duration > 42 h Time since Injection (hours) 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:

36 Insulin Degludec: Characteristics Insulin degludec concentration reaches steady state in 3 days 2 IDeg serum concentration Proportion of Day 6 level (%) Type 1 diabetes Days since first dose Proportion of Day 4 level (%) 120 Type 2 diabetes Days since first dose Variability in glucose-lowering effect over 24 hours at steady state 3 Day-to-day variability (coefficient of variation %) IDeg variability is four-fold lower than IGlar IDeg IGlar Area under the GIR curve (time interval, hours) 1. Heise et al. Diabetes Obes Metab 2012;14:944 50; 2. Heise et al. Diabetes 2012;61(Suppl. 1):A259; 3. Heise et al. Diabetes Obes Metab 2012;14:

37 Degludec U-100 and U-200 are Bioequivalent T1DM (n = 33, adults) 0.4 units/kg once daily Korsatko S et al. Clin Drug Investg,

38 Roger subsequent events Recall: Ø Saw educators Ø Started on basal insulin, given at bedtime Ø Pioglitazone stopped, other meds continued Ø Systematic Monitoring plan Subsequently: Ø Basal insulin titrated to 40 units per day Ø A1C: 7.2% Ø Now complains of occasional hypoglycemia: late morning, late afternoon & nocturnal; often associated with increased activity 38

39 What would you recommend at this time? Breakfast Post- Brkfst Lunch Post- Lunch Supper Sunday Post- Supper Bedtime Monday Tuesday Wednesday Thursday Friday Saturday No change in the pharmacologic treatment 2. Reduce the Basal insulin to reduce the risk of hypoglycemia 3. Add GLP-1 RA, reduce basal insulin, and stop DPP-4i 4. Add premeal insulin at suppertime, reduce basal, Stop DPP-4i 5. Change to fixed mixture insulin BID Metformin ER 1000 mg BID; DPP-4 inhibitor; SGLT2 inhibitor Basal Insulin: 40 units daily at bedtime A1C: 7.2%

40 When It May Be Time to Stop Titrating Basal Insulin Therapy in T2DM? Individual is not meeting glycemic targets on basal insulin 1,2 A1C still not at goal with 0.5 U/kg/day of daily basal insulin A1C not at goal despite target fasting plasma glucose (FPG) with basal insulin usually due to increased PPG Large glucose drops overnight or between meals (suggesting excessive amounts of basal insulin) Nocturnal hypoglycemia 1,2 When further increases in basal insulin result in hypoglycemia 1. Inzucchi S, et al. Diabetes Care. 2012;35: ADA. Practical Insulin: A Handbook for Prescribing Providers. 3rd ed. 2011:

41 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 41

42 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:

43 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 2015;38;

44 A1C Level (%) INITIATE: Basal Analog vs Premixed Analog Change in A1C Level From Baseline to Study End Baseline Endpoint 9.8% 7.4% Insulin Glargine + OADs 2.4% P < % 6.9% Biphasic Insulin Aspart 70/30 Raskin P et al. Diabetes Care. 2005;28(2): % Episodes per Patient Year Documented Hypoglycemic Episodes (<56 mg/dl) Insulin Glargine + OADs P < Biphasic Insulin Aspart 70/30 Total units = 51.3 ± 26.7 with glargine plus OADs vs ± 39.5 with premixed insulin 44

45 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. 45

46 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:

47 Prandial Insulin Lispro: U-200 Humalog [SmPC]. Houten, The Netherlands: Eli Lilly and Company,

48 Concentrated Insulins Brand Product Generic Concentration Device Dosing Max Units/ Increment dose s Units/Device # Devices /Package Expiration After 1st Use Humalog Insulin lispro 200 units/ ml Kwikpen 1 unit 60 units 600 units/pen 2 pens/pkg (1200 units) 28 days Humulin Human 500 units/ Regular ml Vial ,000 units/ vial Kwikpen 5 unit 300 units 1500 unit/pen 1 vial/pkg (10,000 units) 2 pens/pkg (3000 units) 40 days 28 days Toujeo Insulin 300 units/ glargine ml Solostar pen 1 unit 80 units 450 units/pen 3 pens/pkg (1350 units) & 5 pens/pkg (2250 units) 28 days Tresiba Insulin 200 units/ degludec ml FlexTouc h pen 2 units 160 units 600 units/pen 3 pens/pkg (1800 units) 56 days Complements of Alissa R. Segal, PharmD, CDE, CDTC, FCCP 48

49 Inhaled Insulin Indicated for adults with type 1 or 2 diabetes, in combination with long-acting insulin. Ultra-rapid-acting insulin: Onset minutes, peak 60 minutes, duration hrs An inhaled alternative to vial and syringe for meal-time insulins. Type 1 diabetes patients will need a long-acting insulin in addition to prandial insulin. RSS = Rapid-acting analog GIR = Glucose infusion rate Afrezza Package insert; Santos Cavaiola T, Edelman S. Clin Ther. 2014;36:

50 Inhaled Insulin: Limitations and Contraindications Limitations: Inhaled insulin is not a substitute for longacting 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 (Black Box warning) endocrinologicandmetabolicdrugsadvisorycommittee/ucm pdf 50

51 Adding Bolus Insulin Ø Consider adding prandial (mealtime) insulin in about 3-6 months if: A1C is elevated Significant postprandial glucose excursions occur (> 180 mg/dl or > 50 point rise from preprandial) 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;

52 Adding Prandial Insulin to Basal Therapy Further Improves HbA1C Davies M et al Diabetes Obes Metab May;10(5):

53 Adding Bolus Insulin Ø Add prandial insulin before meal with largest glucose excursion (>180 mg/dl) or the meal with the largest CHO content. Ø Other meals can be covered subsequently. Ø Alternatively start with coverage of all three meals at once. Ø TDD: U/kg; 50/50 basal/prandial Ø 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) 53

54 Carbohydrate Counting: Summarized Carbohydrate is the food component that most affects blood glucose Tracks grams of carbohydrate consumed to adjust insulin doses The more carbohydrate consumed, the more insulin taken Particularly useful for people treated with variable premeal doses of rapid-acting insulin Requires pre- and postprandial glucose checks When converting from basal plus, calculate doses from scratch For more information, see: 54

55 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 55

56 Paired Glucose Testing Can Provide Valuable Information to Patients Post-meal Delta Value >50 mg/dl >100 mg/dl <50 mg/dl Interpretation Not enough insulin used to cover carbs Insulin lag time not utilized Illness (flu) Snacking between the meal and 2-hour check time Forgot to give insulin (especially if delta >200 mg/dl) Insulin has expired or is denatured Insulin antibodies forming Insulin-to-carb mismatch Too much insulin (watch for hypoglycemia) Alcohol use (decreases gluconeogenesis) Insulin stacking: consider this option when the delta is NEGATIVE at 2 hours! 56

57 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 57

58 Roger: Summary 47 yo man with 10 years of T2D Also Dyslipidemia Meds initially Metformin Glyburide Pioglitazone SGLT2 inhibitor FH DM Store manager, moderately active at work Initially didn t want insulin 58

59 Roger subsequent events Ø Started on basal insulin, given at bedtime Ø Pioglitazone stopped Ø Other oral antidiabetes medications continued unchanged Ø Monitoring plan: Check 3 times/ day, vary checking systematically pre & post prandial Ø Basal insulin titrated to 40 units per day Ø A1C: 7.2% Ø Now complains of occasional hypoglycemia: late morning, late afternoon & nocturnal; often associated with increased activity 59

60 What would you recommend at this time? Breakfast Post- Brkfst Lunch Post- Lunch Supper Sunday Post- Supper Bedtime Monday Tuesday Wednesday Thursday Friday Saturday No change in the pharmacologic treatment 2. Reduce the Basal insulin to reduce the risk of hypoglycemia 3. Add GLP-1 RA, reduce basal insulin, and stop DPP-4i 4. Add premeal insulin at suppertime, reduce basal, Stop DPP-4i 5. Change to fixed mixture insulin BID Metformin ER 1000 mg BID; DPP-4 inhibitor; SGLT2 inhibitor Basal Insulin: 40 units daily at bedtime A1C: 7.2% 60

61 What would you recommend at this time? Breakfast Post- Brkfst Lunch Post- Lunch Supper Sunday Post- Supper Bedtime Monday Tuesday Wednesday Thursday Friday Saturday Hypos and drops overnight. Postprandial >50 higher à DPP-4i à GLP-1 RA, basal: This targets postprandial time frame more effectively, flexible schedule, Gluc dep insulin sec., hypo s à Basal plus, basal, stop DPP-4i: ± Flexible, hypo risk Ø Consider long-acting basal insulin for more consistency of patterns Metformin ER 1000 mg BID; DPP-4 inhibitor; SGLT2 inhibitor Basal Insulin: 40 units daily at bedtime A1C: 7.2% 61

62 Take-Away Messages Insulin is highly effective but can pose a challenge for both patients and physicians Basal-bolus and CSII insulin regimens require more injections/use of a device, but optimize insulin coverage and glycemic control Insulin regimens and dosing design should be individualized For type 2 diabetes, advance from basal only to fixmixture, or basal plus GLP-1 RA, Basal Plus and then basal/bolus, as indicated Monitoring of glycemic patterns is a key tool to be used to guide therapeutic decisions 62

63 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,