9/6/18. Clinical Updates for Nurse Practitioners and Physician Assistants: Faculty. Disclosures

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1 Clinical Updates for Nurse Practitioners and Physician Assistants: 218 Combination Basal Insulin and GLP-1 RA Therapy: A Physiologic Approach to Diabetes Care Faculty Robert S. Busch, MD, FACE Director of Clinical Research Albany Medical Faculty: Community Endocrine Group Albany, NY Davida F. Kruger, MSN, APN-BC, BC-ADM Certified Nurse Practitioner Henry Ford Health System Division of Endocrinology, Diabetes, Bone and Mineral Disease Detroit, MI Lucia M. Novak, MSN, ANP-BC, BC-ADM, CDTC Director, Riverside Diabetes Center Riverside Medical Associates Adjunct Assistant Professor Uniformed Services University of the Health Sciences Bethesda, MD Ashlyn Smith, MMS PA-C Endocrinology Associates, P.A. Secretary, American Society of Endocrine Physician Assistants Adjunct Assistant Professor, Midwestern University Scottsdale, AZ Mark Stolar, MD Associate Professor of Clinical Medicine Northwestern University Medical School Chicago, IL Jeff Unger, MD, ABFM, FACE Director, Unger Primary Care Medical Group Rancho Cucamonga, CA 2 Disclosures Dr. Busch serves as a speaker for Novo Nordisk, Sanofi, AstraZeneca and Lilly. He also serves as a researcher for Novo Nordisk, Sanofi and AstraZeneca. Ms. Kruger is employed by NIH. She serves as a member of the advisory board for Novo Nordisk, Abbott, Eli Lilly and Company, Sanofi Aventis, Janssen, Dexcom, and Intarcia. She also serves on the Speakers Bureau for Janssen, Valeritas, AstraZeneca, BI/Lilly, Novo Nordisk, Dexcom, Lilly, Abbott, and Insulet. She has received grants/research support to Henry Ford Health System from AstraZeneca, Eli Lilly, Novo Nordisk, Hemsley Foundation, Dexcom, Lexicon, Abbott. Ms. Kruger has stocks from Dexcom. Ms. Novak serves as a speaker for Novo Nordisk, AstraZeneca and Janssen. She is also a member of the advisory board and is a consultant for Novo Nordisk and Sanofi. Ms. Smith is a member of the speaker s bureau and advisory board for Abbott Nutrition. Dr. Stolar serves as a speaker for AstraZeneca. Dr. Unger is on the advisory board for Abbott Diabetes. He is also a consultant for Novo Nordisk and a speaker for Janssen

2 Learning Objectives: 1. Discuss the benefits of a pathophysiologic vs algorithmic approach to type 2 diabetes (T2D) management 2. Utilize effective strategies to overcome barriers to therapeutic intensification and clinical inertia in T2D management 3. Realize the limits of basal insulin therapy in clinical practice and when there is a greater need to address post-prandial hyperglycemia 4. Identify patients who are most likely to benefit from combined basal insulin-glp-1ra therapy as an effective means of combining endogenous/exogenous insulin therapy 4 PRE-TEST QUESTIONS 5 Pre-test ARS Question 1 Please rate your confidence in your ability to identify patients for whom fixed-ratio basal insulin/glp-1 RAs may be appropriate: 1. Not at all confident 2. Slightly confident 3. Moderately confident 4. Pretty much confident 5. Very confident 6 2

3 Pre-test ARS Question 2 How often do you use a physiologic approach to selecting therapy for T2D? 1. Never 2. Rarely 3. Sometimes 4. Often 5. Always 7 Pre-test ARS Question 3 Approximately how many patients with T2D do you see on a weekly basis, in any clinical setting? 1. None > 25 8 T2DM Significantly Reduces Life Expectancy -6.7 years T2DM years History of MI years History of MI/CVA (1) Emerging Risk Factors Collaboration. JAMA. 215;314:52 6. (2) World Heart Federation. df. Accessed August 1,

4 9/6/18 ADA Position Statement On Managing Hyperglycemia Glycemic targets HbA1c < 7.% (mean PG ~15-16 mg/dl [ mmol/l]) Pre-prandial PG <13 mg/dl (7.2 mmol/l) Post-prandial PG <18 mg/dl (1. mmol/l) Individualization is key: Tighter targets ( %) - younger, healthier Looser targets (7.5-8.%+) - older, comorbidities, hypoglycemia prone, etc. Avoidance of hypoglycemia Diabetes Care 212;35: Diabetologia 212;55: ADA Standards of Medical Care in Diabetes American Diabetes Association Diabetes Care 218;41:S73-S

5 Progressive β-cell Dysfunction Is a Key Driver of Progressive Dysglycemia in T2D Deteriorating β-cell function is partially driven by the incretin defect By the time of diabetes onset, up to 8% of β-cell function may be lost 1,2 PPG FPG Normal Glucose Tolerance β-cell Function Impaired Glucose Tolerance Insulin Resistance Insulin Secretion Diagnosis Severity of Glucose Intolerance Time in Years PPG indicates postprandial plasma glucose; FPG, fasting plasma glucose; T2D, type 2 diabetes; 1. Defronzo RA. Diabetes 29;58: ; 2. Fehse F, et al. J Clin Endocrinol Metab 25;9: ; Figure adapted from Kendall DM, et al. Am J Med 29;122(6 Supp):S37-S5 13 Pre-test ARS Question 5 All of the following mechanisms of hyperglycemia in T2D can be targeted by available antidiabetic therapies, EXCEPT: 1. Increased lipolysis 2. Decreased incretin effect 3. Increased glucose reabsorption 4. Increased hepatic glucose production 14 Ominous Octet DeFronzo RA. Diabetes. 29;58:

6 Using Endogenous Insulin to Treat Diabetes The role of incretin based therapies Dpp-4 inhibitors and Glp-1 RA 16 The Incretin Effect is Diminished in T2DM IR Insulin (mu/l) Control subjects (n=8) Incretin Effect 6 12 Time (min) nmol / L IR Insulin (mu/l) T2DM (n=14) 6 12 Time (min) nmol/l Nauck M et al. Diabetologia. 1986;29: Copyright 1986 Springer-Verlag. 17 GLP-1 Secreted From The L-cells of Gut In Response To Carbohydrate Stimulus Courtesy of Primary Care Network and Jeff Unger, MD 18 6

7 DPP-4 Inhibitors and GLP-1 RAs Increase GLP-1 Activity in Different Ways Active GLP-1 DPP-4 GLP-1 RAs act like GLP-1 but are not readily degraded by DPP-4 < 2 min DPP-4 inhibitors increase GLP-1 by preventing degradation Inactive GLP-1 (1) Baggio L, et al. Gastroenterology. 27;132: (2) DeFronzo RA, et al. Curr Med Res Opin. 28;24: (3) Inzucchi SE, et al. Diabetes Care. 215;38: DPP-4 Inhibitors and GLP-1 RAs Increase GLP-1 Activity in Different Ways GLP-1 activity is higher with GLP-1 RAs ( 9 baseline) vs DPP-4 inhibitors ( 2 baseline) Both classes mediate glucose-dependent changes Increase insulin Decrease glucagon GLP-1 RAs also Slow gastric emptying Increase satiety (1) Baggio L, et al. Gastroenterology. 27;132: (2) DeFronzo RA, et al. Curr Med Res Opin. 28;24: (3) Inzucchi SE, et al. Diabetes Care. 215;38: GLP-1 RA Pharmacologic Activity is Higher with GLP-1 RAs than with DPP-4 Inhibitors 75 Baseline Sitagliptin Exenatide twice daily 64 Plasma Level (pm) Added GLP-1 RA Activity 7 Endogenous GLP-1 RA Activity N=61 metformin-treated, evaluable patients. 21 DeFronzo RA, et al. Curr Med Res Opin

8 Incretin Therapies to Treat T2DM Incretin effect is impaired in T2DM Natural GLP-1/GIP have extremely short half-lives Add GLP-1 analogues with longer half-life: Injectables Exendin-4 Based: Exenatide Exenatide QW Lixisenatide Human GLP-1 based: Liraglutide Dulaglutide Semaglutide Block DPP-4, the enzyme that degrades GLP-1: Oral agents Sitagliptin Saxagliptin Linagliptin Alogliptin Drucker. Curr Pharm Des. 21;7(14): Drucker. Mol Endocrinol. 23;17(2): GLP-1 RAs Mimic and Extend Actions of Endogenous GLP-1 Inactivation Concentration Endogenous GLP-1 Rapid Cleavage by DPP-4 Renal elimination Physiologic GLP-1 RAs Delayed Resistance to DPP-4 Resistance to renal filtration Pharmacologic Timing of effects Prandial/early postprandial Prandial/early postprandial Fasting Meier JJ. Nat Rev Endocrinol. 212 Dec;8(12): Case 1: Meet Cherise Cherise is a 38 year old African American female with a 5 yr history of T2D on Glipizide 2 mg/d and metformin 1 Gram BID. She could not tolerate TZDs due to edema and refused to start insulin. Her A1C for the past 2 years has been between 7.9% and 8.8%. Most recent: 9.% History: Dyslipidemia, hypertension, central obesity (BMI 43 kg/m 2 ). She is not concerned about her weight. Strong family history of T2D as her mother and grandmother are both on dialysis and a maternal aunt recently died of a CVA 24 8

9 Case 1:Helping Cherise Succeed PCP suggests initiating insulin Pt feels frustrated that she cannot get a handle on her diabetes and feels that insulin represents weakness She agrees to begin dulaglutide which has an auto injector Two months later, A1C is unchanged (8.6%) Over the next two months she tried her best to diet and exercise but follow up A1C was still 8.6%. PCP now recommends combining GLP-1 + basal insulin. How can the diabetes team provide Cherise with the tools she needs to succeed? 25 Pre-test ARS Question 6 Which of the following is a common clinician misperception regarding the use of injectable agents in patients with T2D? 1. The need to advance therapy is never-ending 2. Clinicians have little time to provide instruction 3. Cost of injectable agents is an issue for some patients 4. Hypoglycemia is a major patient concern with insulin use 26 Barriers to Injectables: The CLINICIAN Side of the Equation Misperceptions The need to advance therapy is never-ending (therapeutic fatigue) Insulin is most appropriate for end-stage treatment Patients don t want to use injectables Reality-based concerns Time demands of instructing patients about injections Unfamiliarity with the variety of devices (eg, various pens) Misplaced blame If only the patient would exercise and lose weight, they wouldn t need insulin Knowledge gaps Role of glucotoxicity in disease progression and therapeutic failure Typical weight changes (gain): insulin Typical weight changes (loss): GLP-1 RA Familiarity with ADA/EASD and AACE Guidelines 27 9

10 Suggestions for Overcoming Fear of Injections Demonstrate the proper way to inject Duluaglutide has an auto injector Semaglutide can be injected once weekly Patients will likely achieve their glycemic targets PLUS loose weight in the process Injections are painless. Don t believe me lets try! Give first injection in office. No need to refer to a CDE for instructions Praise patient after injection for taking the first step towards improving his glycemic control 28 GLP-1 RA Exenatide, Exenatide LAR, Liraglutide, Dulaglutide, Lixisenatide, Semaglutide Mechanism Activates GLP-1 receptor Primary Glucose-dependent insulin secretion physiological Glucose-dependent glucagon secretion action(s) Satiety Slows gastric emptying Advantages Limitations Cost Postprandial glucose excursions Weight Patient training requirements (injectable therapy) Gastrointestinal side effects (nausea, vomiting [less with longer-acting agents]) Hypoglycemia possible when used with insulin, if insulin doses are not reduced High (relative to other generic agents, ie, metformin) Inzucchi SE, et al. Diabetes Care Short-acting Long-acting Medication Adverse Events Dosing Exenatide BID Lixisenatide Liraglutide Exenatide QW FDA Approved GLP-1 RAs Nausea, vomiting, dyspepsia Nausea, vomiting, diarrhea, headache Start 5 mcg twice daily (1 hour before morning and evening meals), may increase to 1 mcg after 1 month Start 1 mcg daily (1 h before 1 st meal of day), may increase to 2 mcg daily after 14 days Nausea, vomiting, diarrhea, Start.6 mg once daily, may increase to 1.2 headache, dyspepsia, fatigue mg after 1 week. Max dose 1.8 mg daily Nausea, diarrhea, headache, dyspepsia, vomiting Dulaglutide Nausea, diarrhea, vomiting Semaglutide 2 mg once weekly Start.75 mg once weekly, may increase to 1.5 mg once weekly Start.25 mg once weekly, may increase to Nausea, vomiting, diarrhea,.5 mg once weekly. Max dose 1 mg per constipation, abdominal pain week *Albiglutide discontinued July Byetta. Summary of Product Characteristics; 2. Lyxumia. Summary of Product Characteristics; 3. Victoza. Summary of Product Characteristics; 4. Marbury T et al. Diabetes 214;63(Suppl.1):A26(11-P); 5. Kapitza C et al. J Clin Pharm 215;55:497 54; 6. Barrington et al. Diabetes Obes Metab 211;13: ; 7. PI Tanzeum 8. Fineman M et al. Clin Pharmacokinet 211;5:65 74; Ozempic prescribing information; Trulicity prescribing information. 3 1

11 Compounds Half-life Comparing GLP-1 RAs: Shorter-acting vs Longer-acting Effects FPG reduction Postprandial hyperglycemia reduction Fasting insulin secretion stimulation Glucagon secretion Weight reduction Potential for nausea Shorter-acting Exenatide BID, lixisenatide a 2-5 hours Modest Strong Modest Reduction Yes Yes Clinical Pearl: Select GLP-1 RAs for T2DM based on the patient s hyperglycemia profile and preferences a Not approved by the FDA for use in the United States. Brunton S. Int J Clin Pract. 214;68(5): ; Fonseca VA. Clin Ther. 214;36(4): ; Kalra S. Diabetes Ther. 214;5(1): Longer-acting dulaglutide, exenatide QW, liraglutide, semaglutide a 12 hours to several days Strong Modest Strong Reduction Yes Yes 31 GLP-1RA added to Metformin: A1C reduction.2 sita and glimip Glim vs Ex sita and pio vs EX PBO vs Lixi Sita vs Dula QW vs Albi BID DPP-4-LIRA EUREXA DURATION-2 GetGoal-M HARMONY-3 AWARD-5 Change in HbHbA1c (%) * * * *.4.9 * 1.1 * * 1.5 * *Significant vs. all comparators Pratley et al. Lancet 21;375: ; Gallwitz et al. Lancet 212;379: ; Bergenstal et al. Lancet 21;376: ; Ahrén et al. Diabetes Care 213;36: ; Ahrén et al. Diabetes Care 214;37: ; Nauck et al. Diabetes Care 214;37: A1C and Weight Change with Sitagliptin vs. Dulaglutide Once Weekly added to Metformin after 52 weeks (AWARD-5) LS Change in HbA1c (%) A1C Reductions (%) Dulaglutide 1.5 mg P< Dulaglutide.75 mg -.39 Sitagliptin 1 mg LS Change in Weight Weight Loss (kg) -3.3 Dulaglutide 1.5 mg P< Dulaglutide.75 mg Sitagliptin 1 mg Nauck M, et al. Diabetes Care

12 Using Exogenous Insulin to Treat type 2 Diabetes Basal Insulins Fasting hyperglycemia vs postprandial hyperglycemia Overbasalization Combining Glp-1 and insulin: Exogenous/endogenous strategies 34 When to Add GLP-1 RA 35 GLP-1 RAs vs Basal Insulin Change in A1C From Baseline, % st 2nd 3rd 4th Exenatide QW Glargine st 2nd 3rd 4th Liraglutide Glargine -4-4 LEAD-5, Liraglutide Effect and Action in Diabetes. Buse JB, et al. Diabetes Obes Metab. 215;17(2): ; Diamant M. Lancet Diabetes Endocrinol. 214;2(6): ; Russell-Jones D, et al. Diabetologia. 29;52(1):

13 After Basal Insulin, Once-Weekly GLP-1 RA vs. Three Times Daily Prandial Insulin: A1C Control Rosenstock J, et al. Diabetes Care After Basal Insulin, Once-Weekly GLP-1 RA vs. Three Times Daily Prandial Insulin: Weight Rosenstock J, et al. Diabetes Care Rationale for GLP-1 RA and Insulin The combination of a GLP-1 RA and insulin may be highly effective for optimal glucose control, ameliorating the adverse effects often associated with insulin Data from clinical studies support the therapeutic potential of GLP-1 RA-insulin combination therapy, typically showing beneficial effects on: glycemic control body weight with a low incidence of hypoglycemia and, in established insulin therapy, facilitating reductions in insulin dose 39 13

14 Using Endogenous Insulin When Exogenous Insulin is Insufficient. Meet Dave: 52 y/o Construction Foreman T2D for 8 years Meds: metformin 1 mg bid, glipizide 1mg bid, and insulin detemir 8 units at 9 PM Fasting blood glucose mg/dl Sometimes misses evening insulin dose when falling asleep on the couch watching TV. Morning glucose seems no different when he misses his second dose. He doesn t check his blood sugar often in the evening because it was over 24 mg/dl on the few times he checked. CGM demonstrates both fasting and diurnal hyperglycemia 4 More about Dave: Dave works 5-1 hour shifts during season and has to drive an hour each way to work. On his days off he helps his brother remodel a house. He has no other defined exercise as his arthritis of both knees is becoming quite symptomatic. His mother and sisters are all obese and all have type 2 diabetes, but only 2 of 5 are on insulin. He has hypertension and hypercholesterolemia, and is an ex smoker having quit 5 years ago when his grandchildren were born 41 Laboratory Assessment A1C 8.9% Fasting blood glucose 165 mg/dl Creatinine 1.5 mg/dl Microalbumin 75 mg/g creat N <35 Tc 19 mg/dl HDL 35mg/dL TG 19mg/dL LDL 117mg/dL 42 14

15 ARS Question: What have we learned about Dave? Which of the following is correct? 1. Given high CV risk a GLP-1 RA or SGLT2 inhibitor is recommended as part of his therapy 2. His beta cell function is gone since he is not responding to glipizide 3. Bolus insulin would control postprandial glucose in this patient more effectively than a GLP-1 RA 4. Addition of an SGLT-2 inhibitor could get this patient close to target 43 ARS Question: What is the next step for Dave to get him to goal? 1. Add pioglitazone 2. Add an SGLT-2 inhibitor 3. Discontinue glipizide and add bolus insulin 4. Discontinue glipizide and add a GLP-1 RA 5. 1 and and 4 44 Intensifying Treatment with Combination Injectable Therapy When added to oral antihyperglycemic therapy, basal insulin alone may not be sufficient for reaching A1C goals, especially as fasting plasma glucose approaches normal levels Basal insulin Essential component of the treatment strategy when A1C target is not achieved despite intensive therapy with 3 antihyperglycemic agents Combination injectable therapy Options for intensified therapy Basal-bolus insulin Basal insulin + GLP-1 RA Inzucchi SE et al. Diabetes Care. 215;38:14-149; Woerle HJ et al. Diabetes Res Clin Pract. 27;77:

16 Avoiding Overbasalization 46 Insulin Titration: Options When Current Therapy is Not Adequate Using 1 Daily Injection of Basal Insulin Basal plus GLP-1 RA 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 47 Combining GLP-1 RA and Basal Insulin Basal insulin analogs Simple to initiate Control nocturnal hyperglycemia and FPG Lower hypoglycemia risk than NPH Can cause weight gain Achieve HbA1c target in ~5% a Complementary actions GLP-1 RAs Simple to initiate Can control FPG and PPG Do not impair α-cell response to hypoglycemia (reduce risks of severe hypoglycemia) Weight-lowering Additive effects Achieve HbA1c target in ~6% a Potential for better overall A1C control a Percentage achieving <7% across baseline HbA1c quartiles for liraglutide and exenatide once weekly vs insulin glargine. Buse JB, et al. Diabetes Obes Metab. 215;17: ; Holst JJ, Vilsbøll T. Diabetes Obes Metab. 213;15:3-14; Vora J, et al. Diabetes Metab. 213;39:

17 Bolus Insulin vs GLP-1 RA in Combination with Optimized Basal Insulin + Metformin Change in Key Endpoints* Exenatide BID Lispro TID *P<.1 for all key endpoints Percent of Patients Safety -2-3 Body Weight (kg) BMI (kg/m 2 ) Waist Circumference (cm) Hip Circumference (cm) Diamant M, et al. Diabetes Care. 214;37; Minor Hypoglycemia Nocturnal Hypoglycemia Serious AEs 49 Pre-test ARS Question 7 A 48-year-old obese woman, 11-year history of T2D, A1C 7.5%. SMBG log shows FBG mg/dl and PBG mg/dl. Antidiabetic mediations: metformin 1 mg bid, glimepiride 2 mg qd, and insulin glargine U1 46 units qhs. She reports frustration with weight-loss efforts and sometimes skips the insulin because she s busy and worried about weight gain and hypoglycemia. What might be appropriate at this time? 1. Increase dose of basal insulin and add DPP-4 inhibitor 2. Discontinue glimepiride and initiate full basal-bolus insulin 3. Discontinue basal insulin and glimepiride and initiate GLP-1 RA and SGLT-2 inhibitor 4. Discontinue basal insulin and glimepiride and initiate fixed-ratio basal insulin/glp-1 RA 5 Approved Fixed-Ratio Combinations of Basal Insulin and GLP-1 RAs GLP-1 RA Liraglutide GLP-1 RA Lixisenatide Insulin Degludec Insulin Glargine IDegLira IGlarLixi 51 17

18 Using Combination GLP-1 RA/Basal Insulin 52 GLP-1 RA/Basal Insulin Fixed-ratio Combination A1c, % IDegLira IDeg Lira 1.8 mg a Initial A1c a Total Trial Population Final A1c a a a a > > Baseline A1c Category, % a a a a > n= a P<.1. N=166 insulin-naïve adults with T2DM (mean A1c, 8.3%; mean BMI, 31.2 kg/m 2 ) uncontrolled on oral agents assigned to IDegLira, insulin degludec, or liraglutide 1.8 mg daily (DUAL I Extension). Gough SC, et al. Lancet Diabetes Endocrinol. 214;2(11): ; Rodbard HW, et al. Diabetes Obes Metab. 216;18(1): Fixed-Ratio IGlarLixi vs Glargine/GlarLixi Add-on to Metformin in T2D Mean Change in A1C SE, % IGlarLixi (n=161) c Glargine (n=162) LS mean difference, -.17% a 95% CI, -.312, Sc LOCF Weeks Mean Change in Body Weight SE, kg IGlarLixi (n=161) c Glargine (n=162) b LOCF Visit Symptomatic hypoglycemia ( 7 mg/dl): 22% with IGlarLixi vs 23% with glargine Incidence of nausea/vomiting was 7.5%/2.5% with IGlarLixi 54 18

19 Dave: Using Combination Injectable Therapy Dave and his PCP agreed that more insulin was not likely to be effective and he admitted that sometimes he took less insulin as he was afraid of such high doses. Glargine/lixisenatide 3 units qam initiated and glipizide discontinued. After 6 weeks, he was tolerating the medication well and A1C decreased from 8.9% to 8.2%. The dose was increased to 45 units. After 3 months, A1C was down to 7.6% and Dave had lost 6 lbs. What now is more important? Further glycemic lowering or reducing CV risk further? 55 Intensifying Diabetes Therapy: Utilizing GLP-1 RA Effectively The need for insulin is intrinsic to a chronic disease that progresses from relative to absolute insulin deficiency over time Postprandial hyperglycemia plays an important and often unmonitored and undertreated role in the progression of diabetes Use of basal insulin at bedtime is an effective means of lowering fasting and diurnal glycemia but does not address postprandial needs The need for basal insulin implies postprandial deficiency as well. GLP-1 RA analogs and short-acting insulin both meet this often unmonitored need but with very different effects on hypoglycemia, weight gain, and beta cell function GLP-1 RA analogs are a very effective means of providing endogenous insulin and a very effective entry into injectable therapy, as well as adjunct to basal insulin when intensified therapy is needed 56 POST-TEST QUESTIONS 57 19

20 Post-test ARS Question 1 After completing this activity, please rate your confidence in your ability to identify patients for whom fixed-ratio basal insulin/glp-1 RAs may be appropriate: 1. Not at all confident 2. Slightly confident 3. Moderately confident 4. Pretty much confident 5. Very confident 58 Post-test ARS Question 2 After completing this activity, how often do you intend to use a physiologic approach to designing therapy for T2D? 1. Never 2. Rarely 3. Sometimes 4. Often 5. Always 59 Post-test ARS Question 3 At what approximate level of A1C does postprandial glucose make a larger contribution to hyperglycemia than fasting glucose? 1. <7% 2. <7.5% 3. >8% 4. >8.5% 6 2

21 Post-test ARS Question 4 All of the following mechanisms of hyperglycemia in T2D can be targeted by available antidiabetic therapies, EXCEPT: 1. Increased lipolysis 2. Decreased incretin effect 3. Increased glucose reabsorption 4. Increased hepatic glucose production 61 Post-test ARS Question 5 Which of the following is a common clinician misperception regarding the use of injectable agents in patients with T2D? 1. The need to advance therapy is never-ending 2. Clinicians have little time to provide instruction 3. Cost of injectable agents is an issue for some patients 4. Hypoglycemia is a major patient concern with insulin use 62 Post-test ARS Question 6 A 48-year-old obese woman, 11-year history of T2D, A1C 7.5%. SMBG log shows FBG mg/dl and PBG mg/dl. Antidiabetic mediations: metformin 1 mg bid, glimepiride 2 mg qd, and insulin glargine U1 46 units qhs. She reports frustration with weight-loss efforts and sometimes skips the insulin because she s busy and worried about weight gain and hypoglycemia. What might be appropriate at this time? 1. Increase dose of basal insulin and add DPP-4 inhibitor 2. Discontinue glimepiride and initiate full basal-bolus insulin 3. Discontinue basal insulin and glimepiride and initiate GLP-1 RA and SGLT-2 inhibitor 4. Discontinue basal insulin and glimepiride and initiate fixed-ratio basal insulin/glp-1 RA 63 21