Diabetes: Three Core Deficits

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Stuart McGee
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Diabetes: Three Core Deficits Fat Cell Dysfunction Impaired

Insulin Resistance in Muscle and Liver Hyperglycemia Impaired

Renal Glucose Reabsorption Insulin resistance Beta-cell

Diabetes Care. 2014;37(Supp1):S81-S90; Wang P, et al.

1 Diabetes: Three Core Deficits Fat Cell Dysfunction Impaired Incretin Function Impaired Appetite Suppression Obesity and Insulin Resistance in Muscle and Liver Hyperglycemia Impaired Insulin Secretion Islet Cell Dysfunction (Alpha/Beta) Increased Renal Glucose Reabsorption Insulin resistance Beta-cell dysfunction Insulin deficiency relative or absolute ADA. Diabetes Care. 2014;37(Supp1):S81-S90; Wang P, et al. Nat Rev Endocrinol. 2015;11:201-12; Abdul-Ghani MA. Am J Manag Care. 2013;13(3 Suppl):S

2 Empower Patients to Become Involved in Their Own Care Help your patients better manage their T2DM by directing them to enroll in PACK Health, free for a limited time. They ll receive: A toolkit in the mail with easy-to-understand information and resources to help them make healthy changes, stick to their medication plan, keep doctor appointments, and more. Plus they ll get a free pedometer Behavior-change support from a dedicated health advisor that understands their condition, how they re feeling, and how to help Have patients visit the URL below and use Promo Code MIQ002 to start better managing their T2DM today Meet Our Patient: Jessica 38-year-old Hispanic woman with a 5-year history of T2DM on maximum sulfonylurea and metformin She could not tolerate TZDs and refused to start insulin Her HbA1C for the past 2 years has been between 7.8% and 8.5%. Most recent: 8.7% Her medical history is significant for dyslipidemia, hypertension, and central obesity (her BMI is 41) She has a strong family history of T2DM; her mother and grandmother are both on dialysis, and a maternal aunt recently died of a CVA What are Jessica s barriers to injectables? How would you overcome these barriers? 2

3 Barriers to Injectables: Clinicians Misconceptions Need to advance treatment is never-ending (therapeutic fatigue) Patients do not want to use injectables Reality-based concerns Time demands of instructing patients about injections Lack of familiarity with the variety of devices (eg, various pens) Misplaced blame If only patients 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 receptor agonists Familiarity with ADA/EASD Ng CJ, et al. Int J Clin Pract. 2015;69: ; Poinski JM, et al. Diabetes Educ. 2013;39:53-65; Benroubi M. Diabetes Res Clin Pract. 2011;93(Suppl 1):S97-9. Barriers to Injectables: Patient / Partner / Caregiver Pain/fear of injections Disease is bad/much worse Misattribution: bad outcomes in others who used insulin Weight gain Loss of control of daily activities (eg, driving, occupation) Hypoglycemia Medication regimen complexity (multi-pill + injection) Loss of privacy (people observe insulin equipment ) Ng CJ, et al. Int J Clin Pract. 2015;69: ; Poinski JM, et al. Diabetes Educ. 2013;39:53-65; Benroubi M. Diabetes Res Clin Pract. 2011;93(Suppl 1):S

4 Combining GLP-1 Receptor Agonists and Basal Insulin Complementary Actions Basal Insulin Analogs Simple to initiate Control nocturnal hyperglycemia and FPG Lower hypoglycemia risk than NPH Can cause weight gain Achieve HbA1C target in ~50% a GLP-1 Receptor Agonists Simple to initiate Can control FPG and PPG Do not impair α-cell response to hypoglycemia (reduce risks of severe hypoglycemia) Weight lowering Achieve HbA1C target in ~60% a Additive Effects Potential for Better Overall HbA1C Control a Percenatge achieving < 7% across baseline HbA1C quartiles for liraglutide and exenatide once weekly vs insulin glargine Buse JB, et al. Diabetes Obes Metab. 2015;17:145-51; Holst JJ, et al. Diabetes Obes Metab. 2013;15:3-14; Vora J, et al. Diabetes Metab. 2013;39:6-15. Comparing GLP-1 Action: GLP-1 Receptor Agonists vs DPP-4 Inhibitors Increases glucose-dependent insulin secretion GLP-1 GLP-1 Receptor Agonist Exenatide Liraglutide DPP 4 Inhibitor Yes Improves first-phase insulin response Yes Yes? Decreases inappropriately elevated glucagon Yes Regulates gastric emptying Yes Yes No Decreases food intake and confers weight loss Yes Yes No Unger J. In: Diabetes Management in Primary Care. Philadelphia, PA: Lippincott, Williams and Wilkins; 2007; DeFronzo RA, et al. Curr Med Res Opin. 2008;24: ; Holst JJ, et al. Diabetes Obes Metab. 2013;15:3-14; Riddle MC, et al. Diabetes Care. 2013;36: ; Richter B, et al. Vasc Health Risk Man. 2008;4:

5 GLP-1 Receptor Agonists: Clinical Characteristics and Glycemic Effects Dosing Frequency HbA1C (%) a FPG (mg/dl) a Magnitude of PPG Effect Exenatide 1,2 Twice a day -0.4 to to Exenatide ER 2-4 Once a week -1.5 to Liraglutide 1,2,5 Once a day -0.6 to to Albiglutide b,6 Dulaglutide b,7,8 Once a week Once a week -0.8 to to to to a Administered as monotherapy or in combination with metformin or other glucose-lowering agents. b Neither albiglutide nor dulaglutide is recommended for first-line therapy. 1. Neumiller JJ. J Am Pharm Assoc (2003). 2009;49:S16-S29; 2. Fineman MS, et al. Diabetes Obes Metab. 2012;14:675-88; 3. Diamant M, et al. Lancet. 2010;375: ; 4. Gerich J. Int J Gen Med. 2013;6:877-95; 5. Buse JB, et al. Lancet. 2009;374:39-47; 6. Pratley RE, et al. Lancet Diabetes Endocrinol. 2014;2:289-97; 7. Dungan K, et al. Lancet. 2014;384: ; 8. Wysham C, et al. Diabetes Care. 2014;37: Intensifying Treatment With Combination Injectable Therapy When added to oral antihyperglycemic therapy, basal insulin alone may not be sufficient for reaching HbA1C goals, especially as FPG approaches normal levels Basal insulin Essential component of the treatment strategy when HbA1C 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 Receptor Agonist Inzucchi SE, et al. Diabetes Care. 2015;38:140-9; Woerle HJ, et al. Diabetes Res Clin Pract. 2007;77:

6 GLP-1 Receptor Agonist and Basal Insulin in T2DM Management: Complementary and Additive Features Basal Insulin GLP-1 Receptor Agonist Primary effects Fasting glucose Postprandial glucose excursions Interprandial glucose Fasting glucose Mechanism Hepatic glucose production Glucose-dependent insulin secretion Non-glucose-dependent endogenous insulin Glucagon secretion Insulin concentration Glucagon secretion Hepatic glucose production Gastric emptying Satiety Food intake Effect on weight Body weight Body weight Modified from Balena R, et al. Diabetes Obes Metab. 2013;15: Efficacy of GLP-1 Receptor Agonist and Basal Insulin Combination Therapy: Meta-Analysis of Randomized Clinical Trials* Outcome Mean difference in HbA1C, % (95% CI) Relative risk of achieving target HbA1C (95% CI) Mean difference in body weight, kg (95% CI) Vs Any Other Antidiabetic Therapy Results No. of Studies Vs Basal-Bolus Insulin Results No. of Studies (-0.60 to -0.29) (-0.17 to -0.02) (1.43 to 2.56) (0.91 to 1.26) (-4.90 to -1.54) (-9.80 to -1.51) 3 Safe and effective Reduces HbA1C without weight gain and with low risk of hypoglycemia Empiric decrease in insulin dose should be made to prevent hypoglycemia in patients with HbA1C 8% *Mean (range) study duration = 24.8 (12-36) weeks; Includes basal-bolus insulin. Eng C, et al. Lancet. 2014;384: ; Carris NW, et al. Drugs. 2014;74: ; Hirsch IB, et al. Postgrad Med. 2014;126:

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7 Comments about today s program? Call toll-free info@med-iq.com To receive credit, read the introductory CME material, watch the Webcast, and complete the evaluation, attestation, and post-test, answering at least 70% of the post-test questions correctly. The evaluation, attestation, and post-test may be accessed by clicking the Get Credit tab at the bottom of the Webcast activity. Please visit us online at for additional activities sponsored by Med-IQ. To sign patients up for the patient engagement program, please click the Patient Engagement Toolkit tab below.elw click the Patient Engagement tab below 2016 Unless otherwise indicated, photographed subjects who appear within the content of this activity or on artwork associated with this activity are models; they are not actual patients or doctors. not actual patients or doctors. 7

8 Abbreviations/Acronyms ADA = American Diabetes Association BMI = body mass index CI = confidence interval CVA = cerebrovascular accident DPP 4 = dipeptidyl peptidase 4 EASD = European Association for the Study of Diabetes ER = extended release FPG = fasting plasma glucose GLP 1 = glucagon like peptide 1 HbA1C = hemoglobin A1C NPH = neutral protamine hagedorn PPG = post prandial glucose T2DM = type 2 diabetes TZD = thiazolidinediones

Multiple Factors Should Be Considered When Setting a Glycemic Goal

Multiple Factors Should Be Considered When Setting a Glycemic Goal Multiple Facts Should Be Considered When Setting a Glycemic Goal Patient attitude and expected treatment effts Risks potentially associated with hypoglycemia, other adverse events Disease duration Me stringent