Against All Odds Improving Insulin Use in T2DM Through Individualized Clinical Decision Making June 16, 2014 1:00 pm 2:30 pm Washington State Convention Center Seattle, WA Educational Partner
Session 4: Against All Odds: Improving Insulin Use in T2DM through Individualized Clinical Decision Making Learning Objectives 1. Summarize the clinical evidence supporting the use of basal insulin therapy, with and without GLP-1 receptor agonists, in the management of type 2 diabetes. 2. Incorporate strategies to overcome barriers to insulin use in the treatment of type 2 diabetes. Faculty Richard E. Pratley, MD Professor, Sanford Burnham Medical Research Institute Senior Scientist Florida Hospital Sanford Burnham Translational Research Institute Orlando, Florida Richard E. Pratley, MD, serves as the medical director of the Florida Hospital Diabetes Institute. He is also a senior scientist at the Florida Hospital /Sanford- Burnham Translational Research Institute for Metabolism and Diabetes, and a professor at the Sanford-Burnham Medical Research Institute at Lake Nona. He is board certified in internal medicine, received his medical degree from Wayne State University in Detroit, and completed fellowships in geriatric medicine and gerontology at the University of Michigan, John Hopkins University and the National Institute on Aging. Dr Pratley is an internationally recognized expert in diabetes. He hosts frequent lectures, has conducted numerous research studies on the pathogenesis, prevention, and treatment of diabetes and published over 150 peer-reviewed articles on diabetes. Dr Pratley is currently a member of the editorial board of The Lancet Diabetes and Endocrinology. Jeff Unger, MD American Board of Family Medicine Director, Metabolic Studies Catalina Research Institute Chino, California Jeff Unger, MD, is currently director of metabolic studies at the Catalina Research Institute in Chino, California. The research center incorporates primary care with clinical research in areas related to diabetes, sexual dysfunction, diabetic neuropathy, diabetic nephropathy, hyperlipidemia, hypertension, pain, obesity and mental illness. A board-certified family physician and a fellow of the American Association of Clinical Endocrinologists, Dr Unger is an international primary care thought leader in the field of diabetes. He has educated patients and clinicians around the world regarding intensive diabetes management through both speeches and his textbook Diabetes Management in Primary Care. An avid writer, Dr Unger has published more than 160 peer-reviewed articles on headaches and diabetes. He also serves on the editorial boards of several medical journals. Carol H. Wysham, MD Clinical Associate Professor of Medicine University of Washington School of Medicine Section Head, Rockwood Center for Diabetes and Endocrinology Spokane, Washington Carol H. Wysham, MD, is the clinical associate professor of medicine at the University of Washington School of Medicine, the research professor at the College of Pharmacotherapy at Washington State University, and the section head of Rockwood Center for Diabetes and Endocrinology in Spokane. She received her medical degree from the University of Iowa College of Medicine, Iowa City. She completed her residency and internship in internal medicine at Oregon Health Sciences University, Portland, and a fellowship in endocrinology and metabolism at the University of Iowa Hospitals and Clinics. Dr Wysham has served as chair of the Professional Practice Committee of the American Diabetes Association and has been involved in multiple clinical trials, including the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial and the Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes (AIM-HIGH) trial.
Faculty Financial Disclosure Statements The presenting faculty reported the following: Richard E. Pratley, MD, receives research grants from Gilead Sciences, GlaxoSmithKline, Lilly, Mannkind Corporation, Merck & Co., Novo Nordisk, Pfizer, Inc., and Takeda Pharmaceuticals. He participates in speakers' bureau for Boehringer Ingelheim, Merck & Co., Novo Nordisk, and Takeda Pharmaceuticals. He receives honoraria from AstraZeneca/BMS, Boehringer Ingelheim, Eisai, GlaxoSmithKline, Janssen Pharmaceuticals Ltd., Lexicon, Mannkind Corporation, Merck & Co., Novo Nordisk, Profil Institute, Sanofi-Aventis US, LLC, and Takeda Pharmaceuticals. He serves as a consultant for Amylin Pharmaceuticals, LLC, AstraZeneca/BMS, Boehringer Ingelheim, Eisai, Gilead Sciences, GlaxoSmithKline, ICON Clinical Research, Inc., Janssen Pharmaceuticals Ltd., Ligand Pharmaceuticals, Inc., Lilly, Mannkind Corporation, Merck & Co., Novo Nordisk, ONO Pharmaceuticals, Profil Institute, Sanofi-Aventis US, LLC, and Takeda Pharmaceuticals. Jeff Unger, MD, participates in speakers' bureau for Janssen Pharmaceuticals, Novo Nordisk and Valeritas. He serves as an advisor or consultant for Dance Pharmaceuticals, Halozyme, Johnson and Johnson, Novo Nordisk, Sanofi-Aventis and Valeritas. He receives grants for clinical research from BI, GSK, Johnson and Johnson, Lilly, Novo Nordisk, Pfizer and Sanofi- Aventis. He receives payment for clinical trials program from Catalina Research Institute. Carol H. Wysham, MD, participates in speakers bureau for AstraZeneca/BMS Boehringer-Ingelheim, Janssen, Pharmaceuticals, Novo Nordisk, and Sanofi Aventis. She participates in advisory boards for AstraZeneca/BMS, Eli Lilly, and Janssen Pharmaceuticals. Education Partner Financial Disclosure Statement The content collaborators at Vindico Medical Education have reported the following: Ronald A. Codario, MD, FACP, RPVI, FNLA, CCMEP, medical director, has no relevant financial relationships to disclose. Jennifer Frederick, PharmD, scientific director, has no relevant financial relationships to disclose. Suggested Reading List Garber AJ, Abrahamson MJ, Barzilay JI, et al. AACE comprehensive diabetes management algorithm 2013. Endocr Pract. 2013;19(2):327-336. American Diabetes Association. Standards of medical care in diabetes 2013. Diabetes Care. 2013;36(Suppl 1):S11-S66. Siminerio L. Barriers, solutions to insulin injection therapy for type 2 diabetes. Endocrine Today. February 2013. http://www.healio.com/endocrinology/diabetes/news/print/endocrine-today/%7beaff2ca5-d457-4f76-8b63-24d6f9d02760%7d/barriers-solutions-to-insulin-injection-therapy-for-type-2-diabetes Coulter FC. Early Insulin Initiation A Review of the Literature and Case Studies. The Internet Journal of Family Practice. 2012;10(1). Meneghini LF. Intensifying insulin therapy: what options are available to patients with type 2 diabetes? Am J Med. 2013;126(9 Suppl 1):S28-S37. Mohebi S, Azadbakht L, Feizi A, et al. Review the key role of self-efficacy in diabetes care. J Educ Health Promot. 2013;2:36.
SESSION 4 1 2:30pm Against All Odds: Improving Insulin Use in T2DM Through Individualized Clinical Decision Making SPEAKERS Richard Pratley, MD Jeff Unger, MD, FACE Carol Wysham, MD Presenter Disclosure Information The following relationships exist related to this presentation: Richard Pratley, MD, receives research support from Gilead, Lilly, Novo Nordisk, sanofi, Takeda and is a consultant for Astra-Zeneca, BMS, Boehringer Ingelheim, Gilead, GSK, Lilly, Merck, Novo Nordisk, Sanofi- Aventis, and Takeda. Jeff Unger, MD, FACE, participates on the speakers bureau for Janssen Pharmaceuticals, Novo Nordisk and Valeritas; advisory board for Novo Nordisk, Johnson and Johnson, Valeritas, Halozyme, Sanofi-Aventis, Dance Pharmaceuticals; and receives research grants from Boehringer Ingelheim, Novo Nordisk, GSK, Lilly, Johnson and Johnson, Pfizer, and Sanofi-Aventis. Carol Wysham, MD, participates on the speakers bureau for Bristol-Myers Squibb/Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Novo Nordisk, Sanofi-Aventis; and receives consulting fees from Bristol-Myers Squibb/Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen, and Sanofi- Aventis. Presenter Disclosure Information Off-Label/Investigational Discussion In accordance with pmicme policy, faculty have been asked to disclose discussion of unlabeled or unapproved use(s) of drugs or devices during the course of their presentations. Against All Odds: Improving Insulin Use in T2DM Through Individualized Clinical Decision Making Learning Objectives Summarize the clinical evidence supporting the use of basal insulin therapy, with and without GLP-1 receptor agonists, in the management of type 2 diabetes. Incorporate strategies to overcome barriers to insulin use in the treatment of type 2 diabetes. Incorporating the New AACE Comprehensive Diabetes Management Algorithm Richard Pratley, MD Samuel Crockett Chair in Diabetes Research Director, Florida Hospital Diabetes Institute Senior Scientist, Translational Research Institute Adjunct Professor, Sanford Burnham Medical Research Institute Orlando, FL 1
Goals and Objectives 1. Utilize a case based, practical approach to allow you to effectively employ basal insulin in your patients with T2DM 2. Interactive cases will illustrate: a) How to use the latest guidelines b) When and how to use basal insulin with and without GLP-1 receptor agonists and in combination with other anti-diabetic agents c) What you need to know about safety issues Case 1: Maria 52-year-old Latina woman obese with T2DM for 14 years She is presently taking metformin 1000 mg BID, glimepiride 4 mg BID, sitagliptin 100 mg daily She comes to the office complaining of increased tiredness and elevated fasting blood sugars in the 180 to 200 mg/dl range Her A1C now is 9.8% (eag 235 mg/dl) eag=estimated average glucose Decline in -Cell Function with Diabetes Progression: UKPDS How to Start Insulin Therapy When Oral Antidiabetic Drugs Fail in Patients with T2DM 100 75 Rx: Insulin, Metformin, Sulfonylurea Basal Insulin Therapy -Cell Function (%) 50 25 IGT Postprandial Type 2 Hyperglycemia Diabetes Phase I Type 2 Diabetes Phase II Type 2 Diabetes Phase III 0-12 -10-6 -2 0 2 6 10 14 Years from Diagnosis Dashed line shows extrapolation forward and backward from years 0 to 6 based on HOMA data from UKPDS. Lebovitz H. Diabetes Rev. 1999;7(3):139-153. UKPDS 16. Diabetes.1995;44:1249-1258. OADs = oral antidiabetic drugs Combination of 2 or 3 OADs Lifestyle changes plus metformin Idealized Profiles of Basal Insulin Analogs So, When Do You Add Insulin? Plasma Insulin Levels NPH Detemir Glargine ADA/EASD and AACE consensus statements agree: Lifestyle modification + 1 to 2 oral/non-insulin injectable (in 3-month increments/changes) and fail to achieve goal A1C level 0:00 2:00 4:00 6:00 8:00 10:00 12:00 14:00 16:00 18:00 20:00 22:00 24:00 Time Rosenstock, Goldstein BJ, et al, eds. Textbook of Type 2 Diabetes. London, UK, and New York, NY: Martin Dunitz; 2003:131-154; Plank J et al. Diabetes Care. 2005;28:1107-1112. Practical Insulin: A Handbook for Prescribing Providers. ADA. Third Edition. 2011. Start basal insulin to achieve glucose targets Inzucchi SE, et al. Diabetes Care. 2012;35:1364-1379. Garber AJ, et al. Endocr Pract. 2013;19(2):327-336. 2
Are There Any Other Reasons to Start Insulin Sooner? Reasons for Clinical Inertia Individuals presenting with very high glucose levels (>300 mg/dl) Glucotoxicity A1C >9% Symptomatic patients with ketonuria and in a catabolic state Lack of education, training, and practice organization to achieve goals Need for combination therapy Familiarity with algorithms Use of preventive medicine checklists Courtesy of Frank Lavernia, MD Phillips LS, et al. Ann Intern Med. 2001;135(9):825-834. Reasons for Clinical Inertia How to Adjust Insulin Overestimation of care Soft reasons for lack of intensification Perception of improving control Dietary non-adherence Translatability of clinical research findings Drug side effects and interaction Patient aversion to medical therapy Identify target blood glucose goals Emphasize importance of eating consistently when trying to determine insulin adjustment and pattern management, especially carbohydrates Determine basal insulin doses by looking for blood glucose patterns Phillips LS, et al. Ann Intern Med. 2001;135(9):825-834. Case 1: Maria Following a discussion of the advantages and precautions about using insulin therapy, you begin Maria on a long-acting basal insulin analog, continuing metformin 1000 mg BID, glimepiride 4 mg BID, sitagliptin 100 mg daily She is advised to self monitor her fasting After 4 weeks her A1C now is 8.0% (eag 183 mg/dl) Initiating and Titrating Basal Insulin Detemir INITIATION: 10 units or 0.1 to 0.2 units/kg daily TITRATION: Assess mean 3-day fasting plasma glucose and adjust every 3 days according to the following schedule: If fasting plasma glucose goal is 70 to 90 mg/dl: 1) Add 3 units if FPG is >90 mg/dl 2) No Change if FPG is 70 to 90 mg/dl 3) Reduce dose by 3 units if FPG is <70 mg/dl If fasting plasma glucose goal is 80 to 110 mg/dl: 1) Add 3 units if FPG is >110 mg/dl 2) No Change if FPG is 80 to 110 mg/dl 3) Reduce dose by 3 units if FPG is <80 mg/dl eag=estimated average glucose Blonde L, et al. TITRATE STUDY GROUP. Diabetes Obes Metab. 2009;116:623-631. 3
Initiating and Titrating Basal Insulin Glargine Take Home Points INITIATION: 10 units daily TWO SUGGESTED TITRATION OPTIONS: 1) Increase dose by 2 units every 3 days until individualized target fasting plasma glucose is achieved OR 2) Increase by 1 unit every day until fasting plasma glucose <100 mg/dl or individualized target fasting plasma glucose is achieved AACE algorithms recommend use of insulin if not at goal within the first year of treatment Basal insulin is titrated to a target FPG Insulin can be used in combination with other agents Stop titration of basal insulin when fasting plasma glucose goals are achieved or with warning signs of Nathan DM, et al. Diabet Med. 2009:52(10):17-30. Davies M, et al. ATLantus Study Group. Diabetes Care. 2005:28(6) 1282-1288. Gerstein HC, et al. Diabet Med. 2006;23(7);736-742. Yki-Jarvinen H, et al. Diabetes Care. 2007:30(6):1364-1369. Case 2: Eloise Addressing Post-Prandial Hyperglycemia in Patients Taking Basal Insulin Jeff Unger, MD, FACE Medical Director Unger Primary Care Medical Center Chino, CA 60-year-old African-American female with hypertension and T2DM for 11 years Current medications: metformin 1000 mg BID, glipizide XL 10 mg once daily, insulin detemir 25 units daily and olmesartan/hct 20/12.5 once daily She tells you: Doctor, I am always hungry, and my sugar is frequently in the 200 to 225 range after supper. Lab data: BMI 30 kg/m 2 ; BP 146/94 mmhg bilaterally A1C 8.2%; Post supper glucose 201 to 243 mg/dl; Pre-breakfast glucose 108 to 125 mg/dl Triglycerides: 249 mg/dl; HDL-C 42 mg/dl; LDL-C 113 mg/dl; Total cholesterol 205 mg/dl egfr 85 ml/min When Basal Insulin, Metformin, and Secretagogues are Not Enough: What is the Next Strategy? Individualize treatment to patient s needs: Add or substitute premix insulin Add bolus insulin analogue Add GLP-1 receptor agonist Add SGLT2 inhibitor Optimizing Insulin Therapy for Maintenance of Glycemic Control When Basal is Not Enough Basal Bolus Add prandial insulin before meals Basal Plus Add prandial insulin at main meal Basal Add basal insulin and titrate SGLT2 Inhibitors Basal plus DPP-4 inhibitors or GLP-1 receptor agonists Raccah D, et al. Diabetes Metab Res Rev. 2007;23:257-264. Garber AJ, et al. Endocr Pract. 2013;19(2):327-336. Lifestyle changes plus metformin (± other agents) 4
Insulin in Combination With Other Agents SGLT2 Inhibitors Insulin + GLP-1 receptor agonists Insulin + DPP-4 inhibitors Insulin + SGLT2 inhibitors Oral agents: canagliflozin, dapagliflozin Efficacy: Moderate A1C improvement (average A1C reductions 0.6% to 0.9%) Reduce systolic and diastolic blood pressure Weight loss (2 to 4 kg) Safety: No added unless used with secretagogues and/or insulin Increases LDL-C and non-hdl-c (canagliflozin) Dapagliflozin not indicated for egfr < 60 ml/min/1.73m 2 Canagliflozin not indicated for egfr < 45 ml/min/1.73m 2 Yale J, et al. Diabetes Obes Metab. 2013;15:463-473. DPP-4 Inhibitors 24-Hour Plasma Glucose Curve: Normal and Type 2 Diabetic Subjects Efficacy: Moderate A1C improvement Higher potency when combined with metformin Weight neutral Improved CV risk profile Safety: No added unless used with sulfonylurea No GI side effects Dosing adjustments for renal dysfunction EXCEPT linagliptin Deacon CF and Holst JJ. Expert Opin Pharmacother. 2013;14:2047-2058. Glucose (mg/dl) Courtesy of J. Skyler 400 300 200 100 0 0600 1000 1400 1800 2200 0200 0600 Time of Day Adapted from Polonsky KS, et al. N Engl J Med. 1988;318(19):1231-1239. Diabetic Normal Plasma Insulin Levels Idealized Profiles of Human Insulin and Analogs Rapid-acting: lispro, aspart, glulisine Regular insulin NPH Detemir 0:00 2:00 4:00 6:00 8:00 10:00 12:00 14:00 16:00 18:00 20:00 22:00 24:00 Time Glargine Rosenstock J, et al, eds. Textbook of Type 2 Diabetes. Martin Dunitz;2003:131-154. Plank J, et al. Diabetes Care. 2005;28:1107-1112. Hypoglycemic Events: NPH vs Detemir Hypoglycemia event number All events 400 350 300 250 200 150 100 50 0 0 2 4 8 12 16 20 24 Time (Study Week) NPH Detemir Compared with NPH insulin, the risk for all with insulin detemir was reduced by 47% (P<0.001) and nocturnal by 55% (P<0.001) Hypoglycemia defined as plasma glucose 72 mg/dl with symptoms or single plasma glucose <56 mg/dl. Hermansen K, et al. Diabetes Care 2006; 29:1269 1274. 5
Ideal Insulin Replacement Pattern Patients With Type 2 Diabetes May Spend 12 Hours Per Day in the Postprandial State 75 Breakfast Lunch Dinner Postprandial Postabsorptive Fasting Duration of Postprandial State Plasma Insulin (U/mL) 50 25 Basal Mealtime Breakfast Lunch Dinner Midnight 4 AM Breakfast 4:00 8:00 12:00 16:00 20:00 24:00 4:00 Time Mudaliar S, et al. Endocrinol Metab Clin North Am. 2001;30:935-982. 8 AM 11 AM 2 PM 5 PM Adapted from Monnier L. Eur J Clin Invest. 2000;30(suppl 2):3-11. Contribution (%) 80 60 40 20 Relative Contributions of Postprandial and Fasting Hyperglycemia Related to A1C PPG Becomes More Important to Control in Type 2 Diabetes as A1C Level Improves PPBS FBS 0 1 (<7.3) Monnier L, et al. Diabetes Care. 2003;26:881-885. 2 3 (7.3 to 8.4) (8.5 to 9.2) A1C quintiles 4 (9.3 to 10.2) PPBS FBS 5 (>10.2) Insulin Analogs Rapid-acting (mealtime) Insulin aspart Insulin glulisine Insulin lispro Long-acting (basal) Insulin detemir Insulin glargine Insulin Analogs (cont d) 1.2.3 Study: Glargine Plus 1, 2, or 3 Doses of Glulisine Pre-mixed analogs Insulin aspart protamine and insulin aspart Insulin lispro protamine and insulin lispro HbA 1c (%) 10.0 9.0 8.0 Evolution of A1C in the randomized population (n=343) Glargine (alone) 10.19 10.19 10.16 Glargine plus glulisine (patients with A1C >7%) Glulisine 1x Glulisine 2x Glulisine 3x 7.44 7.40 7.29 7.0 Run in Randomization Wk 8 Wk 16 Wk 24 } 0.15 Davidson MB, et al. Endocr Pract. 2011;17(3):395-403. 6
How to Initiate Basal-Plus 1 Regimen Start with one dose at largest/main meal - generally dinner Continue metformin + stop insulin secretagogues Encourage patient to keep journal to track BG patterns Testing in pairs bedtime and AM Start with 4 units or 10% of basal dose Consider decreasing basal dose by same amount Instruct patient to increase by 1 to 2 units every 1 to 3 days until HS BG is in goal (120 to 150 mg/dl) Adapted from Nathan DM, et al. Diabetes Care. 2009;32(1):193-203. Use of Twice-Daily Exenatide in Basal Insulin Treated Patients with T2DM Change in HbA1c Level (%) 0.0 0.5-1.0-1.5-2.0-2.5 Change in A1C Over 30 Weeks Insulin glargine + placebo Insulin glargine + exenatide * * 0 10 20 30 Week Change in A1C over 30 weeks. Data are least-squares means estimated from a mixed model, in which the post-baseline response variable = treatment + pooled investigator + visit + baseline + (treatment visit), and the participant is treated as a random effect with an unstructured covariance matrix. Error bars are 95% CIs. * P <.001 for between-group comparisons. Buse JB, et al. Ann Intern Med. 2011;154(2):103-112. Using Basal Insulin with GLP-1 Receptor Agonists Case 2: Eloise Complementary features of basal insulin and GLP-1 receptor agonists Primary effects Mechanisms Basal Insulin Fasting glucose Interprandial glucose Hepatic glucose production Non-glucose dependent endogenous insulin Glucagon secretion Insulin concentration GLP-1 receptor agonist Postprandial glucose excursions Fasting glucose Effect on weight Body weight Body weight Glucose-dependent insulin secretion Glucagon secretion Hepatic glucose production Gastric emptying rate Satiety Food intake Eloise would initially like to try a GLP-1 receptor agonist added to her basal insulin She does not have any contraindications, is already using a basal insulin pen, and likes the idea of possibly losing weight in addition to having something to curb her appetite. Balena R, et al. Diabetes Obes Metab. 2013;15(6):485-502. Therapeutic Rationale Using Insulin and GLP-1 Receptor Agonists Advantages of GLP-1 receptor agonist compared to other possible therapies in this patient: 1. Weight reduction (weight gain with insulin; weight neutral with DPP-4 inhibitor) 2. Reduced postprandial lipemia and hypertriglyceridemia (increased LDL-C and non-hdl-c with SGLT2 inhibitors) 3. Low risk of (increased risk with secretagogues and insulin) 4. Blood pressure reduction (SGLT2 inhibitors also lower blood pressure no direct effects with other agents) 5. Increased satiety (not seen with other agents) the patient needs help curbing her appetite Balena R, et al. Diabetes Obes Metab. 2013;15(6):485-502. Intensive insulin regimens are associated with a higher risk of and weight gain Perfetti R. Diabetes Technol Ther. 2011;13(9):873-881. Basal insulin in combination with GLP-1 receptor agonists improve A1C and postprandial glucose with weight loss and no marked increase in the risk of 7
Which to Use First Insulin or GLP-1 Receptor Agonist? Take Home Points Starting with GLP-1 receptor agonist and then adding insulin (if necessary): 1) May allow potential nausea associated with GLP-1 receptor agonist to diminish before starting insulin 2) Avoids challenges of down-titrating insulin 3) May avoid or delay insulin use Adding GLP-1 receptor agonist to basal insulin: 1) Attenuates weight gain 2) Improves post prandial glycemic control and lowers A1C Patients can successfully self-titrate basal insulin Basal insulin analogues provide a relatively peakless, more physiological time-action profile than NPH insulin GLP-1 receptor agonists plus long-acting basal insulin provide an attractive combination to control fasting and postprandial glucose, while attenuating weight gain and suppressing appetite An individualized approach is always best, balancing convenience of basal-only or premix regimens with the control achievable by more complex regimens including combinations with other agents Grunberger G. J Diabetes. 2013;5:241-253. Vora J, et al. Diabetes Metab. 2013;39:6-15. Insulin Therapy: Addressing Safety and Patient Concerns Carol Wysham, MD Clinical Associate Professor of Medicine University of Washington School of Medicine Research Professor at the College of Pharmacotherapy Washington State University Section Head, Rockwood Center for Diabetes and Endocrinology Spokane, WA Objectives Review the evidence regarding diabetes therapies and their effects on weight gain and Advance your skills in counseling patients on insulin injections, devices, and techniques Improve your approaches for individualizing diabetes therapy to improve adherence Case 3: Alice 58-year-old African-American female with 7 year history of T2DM on metformin 1000 mg BID and glimepiride 4 mg QAM. She works as a salesperson in a department store. She struggles with her weight. Finances are tight. At her previous visit, 6 months ago, her A1C was 7.6%. You suggested insulin, but she begged you to try diet and exercise. You reluctantly agree. Case 3: Alice Follow-up Visit She returns for follow up. She admits that she has not been able to make significant changes in her diet and exercise. Her weight is unchanged at 198 lbs. Her A1C is 7.9%. Again you suggest basal insulin as an option. She starts to cry. 8
Patient Barriers to Insulin Therapy Patient Willingness to Start Insulin Therapy Fear of injection Fear of Weight gain Feelings of failure Association of insulin with poor prognosis Stigma Concerns about fitting it into their lifestyle Cost More frequent monitoring What you say (and how you say it) makes a difference! Peyrot M. Diab Care 2005;28:2673-2679. Provider Barriers To Insulin Therapy Addressing Patient Barriers to Insulin Initiating insulin takes time Management more complicated Lack of resources Increased risk for Fear of increased CVD risk ORIGIN study refutes this Weight gain, worsening insulin resistance Patient resistance Explain progressive nature of disease and need for progressive changes in treatment at initial and follow up visits Discuss likely need for insulin from the outset If patient elicits a negative response, explore it and try to dispel concerns Never use insulin as a threat Take care with your words/actions Weight Has Negative Impact Beyond Therapeutic Goals in Those With T2DM Weight Changes with Antihyperglycemic Agents Added to Metformin: Meta-Analysis Worry about weight has been associated with poorer outcomes, such as greater likelihood of 1 Symptomatic hyperglycemia Suboptimal therapy adherence Poor psychological well-being Diabetes-specific stress Weight gain has been associated with 2 Lower treatment satisfaction Lower health-related quality of life 1 Peyrot M, et al. Curr Med Res Opin. 2009;25:1985-1993. 2 Marrett E, et al. Diabetes Obes Metab. 2009;11;1138-1144. Liu SC, et al. Diabetes Obes Metab. 2012;14:810-820. 9
Weight Gain Minimized by Metformin Change in Weight in Treat-to-Target Studies Using Basal Insulin Mean weight gain (kg) Without metformin 2.8 With metformin 0 Yki-Järvinen Avilés- Santa Bergenstal Insulin Insulin + metformin Insulin Insulin + metformin Insulin Insulin + metformin Number of subjects 24 19 22 21 22 20 Duration of study (months) 12 12 6 6 4 4 Insulin dosage at end (U/d) 53 36 120 92 136 99 A1C at end (%) 7.9 7.2 7.6 6.5 7.0 7.1 Weight gain (kg) 4.6 0.9* 3.2 0.5 0.5-1.4 Change in weight from baseline (kg) 3.5 3 2.5 2 1.5 1 0.5 0 Riddle 2003 1 24 weeks * P < 0.001 Hermansen 2006 2 24 weeks Glargine pm NPH pm Detemir pm NPH twice daily Yki-Järvinen H, et al. Ann Intern Med. 1999;130:389-396. Avilés-Santa L, et al. Ann Intern Med. 1999;131:182-188. Bergenstal RM, et al. Diabetes. 1998;47(suppl 1):A89. Abstract 347. * P < 0.0001 P = 0.07 1 Riddle MC, et al. Diabetes Care. 2003 ;26(11):3080-6. 2 Hermansen K, et al. Diabetes Care. 2006 ;29(6):1269-74. Classification of Hypoglycemia Hypoglycemia in Insulin Treated Patients with T2DM Severe Documented symptomatic Asymptomatic Probable symptomatic Pseudo Assistance required from another person Typical symptoms of with measured plasma glucose 70 mg/dl No typical symptoms of but measured plasma glucose 70 mg/dl Typical symptoms of but no measured plasma glucose available Typical symptoms of with measured plasma glucose > 70 mg/dl Mild (events per week) 0.4 to 0.7 Hypoglycemia unawareness (%) 49 to 64 Patient rarely or never reports to providers (%) 50 to 59 Provider does not ask about during routine appointment (%) 26 Note: pseudo was previously defined by Cryer et al (2009) as an artifact after a blood sample was drawn. Pseudo as defined here was previously called relative. Cryer PE, et al. J Clin Endocrinol Metab. 2009;94:709-728. Seaquist ER, et al. Diabetes Care. 2013;36:1384-1395. Ostenson C. Diabet Med. 2014;31(1):92-101. Hypoglycemia: Antihyperglycemic Agents Added to Metformin Increased risk vs placebo Case 3: Alice Starting Insulin She agrees to try basal insulin Due to finances, you start her on NPH insulin 10 units at bedtime You ask your medical assistant to show her how to inject, using a pen, and to review self-titration. She gives herself a small dose in the office You ask her to return in 4 weeks Liu S, et al. Diabetes Obes Metab. 2012;14:810-820. 10
Appropriate Titration Is Critical to the Success of Insulin Therapy ADA/EASD consensus algorithm for the initiation and adjustment of a basal insulin regimen is indicated as follows: Simplest Titration Option (The Goal Should be Individualized) Increase by 1, REPEAT unit every day; continue until FPG Target 130 mg/dl* (or higher, as appropriate) Start with a long-acting basal insulin Initiated at 10 units/day or 0.2 units/kg/day NOTE: Dosage should not be increased that week if there are any episodes of documented (<72 mg/dl) during the preceding week. Check fasting glucose daily and increase dose by: 2 units every 3 days until fasting levels are in target range (70 to 130 mg/dl) Nathan DM, et al. Diabetes Care. 2009;32(1):193-203. In the Treat to Target Study Median Insulin dose = 0.48 U/kg *Adjust dose subsequently to patient s need. Modified from Gerstein HC, et al. Diabet Med. 2006;23:736-742. Case 3: Alice Follow-up Visit She did well for two years, but changed to insulin detemir due to occasional nocturnal. Current dose is 50 units at bedtime. Weight: 201 pounds A1C: 7.9% As requested, she brings in SMBG records. Case 3: Alice SMBG RESULTS B FAST LUNCH DINNER HS MON 128 TUES 118 WED 136 THURS 128 FRI 88 162 175 307 SAT 142 226 SUN 123 188 265 WHAT NEXT? Objectives Insulin Syringes Review the evidence regarding diabetes therapies and their effects on weight gain and Advance your skills in counseling patients on insulin injections, devices, and techniques Improve your approaches for individualizing diabetes therapy to improve adherence Insulin syringes come in 3 volumes: 1 cc (100 units), ½ cc (50 units), and 0.3 cc (30 units) 11
Steps to Injecting Insulin with a Pen Insulin Delivery Modes Insulin Pens/Devices Put a needle on the pen Dial up and discard 2 units to prime the pen Dial up dose Inject (no pinch needed) in abdomen, arm or leg Count five seconds before withdrawing Pen Needles Not All The Same! Objectives Nano Mini Short Original Equivalent glycemic control REGARDLESS of BMI Strong preference for shorter needles Ease of use, pain, overall preference Hirsch LJ. Curr Med Res Opin. 2010;26:1531 1541. Review the evidence regarding diabetes therapies and their effects on weight gain and Advance your skills in counseling patients on insulin injections, devices, and techniques Improve your approaches for individualizing diabetes therapy to improve adherence (Not actual size) Keys to Facilitating Behavior Change Strategies to Address Patients Concerns About Insulin Therapy Patient-Centered Communication Focus on the person, not the disease Explore feelings many patients with diabetes feel shock, guilt, anger, anxiety, depression, and helplessness Goal-Setting Model Explore the problem Clarify feelings and meaning Develop a plan Commit to action Experiment with and evaluate the plan Communication Model Ask Listen Empathize Encourage Ask open-ended questions to help patient: 1. Reflect on areas of concern or behaviors 2. Identify actions to address the problem or behavior Barrier Sense of control Belief that means diabetes more serious Sense of personal failure Injection-related anxiety Fear of weight gain Fear of Strategies to Address Concerns Insulin treatment helps control glucose Explain progressive insulin deficiency Show that insulin can be used at any point Beta-cells are failing, not the patient Show patient a needle Hurts less than finger sticks Insulin pens are very easy to use Starting insulin early less weight gain Start with basal insulin (? detemir) Lifestyle efforts can mitigate weight gain Discriminate between minor and serious Use insulin analogues Address adjustment of regimen for activity, diet Funnell MM. Family Practice. 2010;27:i17 i22. Modified from Peyrot M. Prim Care Diab 2010 4(suppl 1) S11 S18. 12
Take Home Points Treatment goals and insulin regimens must be individualized. Use shared decision making. Basal insulin is usual first option Basal + 1 or premixed are reasonable next step Consider when: A1C >7% and FBG < 130 mg/dl Basal insulin dose >0.5 units/kg HS BG >> FBG Consider addition of GLP-1 receptor agonist, especially short-acting ones Remember you can always negotiate a 1 month trial Questions? 13