Dr. John Bucheit, Pharm.D., BCACP, CDE Clinical Assistant Professor Mercer University College of Pharmacy

Transcription

1 Dr. John Bucheit, Pharm.D., BCACP, CDE Clinical Assistant Professor Mercer University College of Pharmacy

2 Disclosures to Participants Requirements for Successful Completion: For successful completion, participants are required to be in attendance in the full activity, complete and submit the program evaluation at the conclusion of the educational event. Conflicts Of Interest and Financial Relationships Disclosures Planners: Katie Mick, MS, RD, LD, CDE- None Vicki Karnes, RD, CDE- None LaShonda Hulbert, MPH- None CaSonya Green, MA, CHES- None Benicia Malone, MEd., ACSM CEP, CHES- None Bethany Jagdharyy, RN, BSN, CDE- None Presenter: Dr. John Bucheit, Pharm.D., BCACP, CDE Disclosure of Relevant Financial Relationships and Mechanism to Identify and Resolved Conflicts of Interest: Educational Planning Table was reviewed for bias and found to be unbiased. Keeping the presentation unbiased was discussed with presenter multiple times, AADE speaker guidance letter was sent, speaker signed Bio/COI form, slides will be reviewed prior to program to assess bias, and class will be closely monitored for bias. Sponsorship / Commercial Support: None Non-Endorsement Of Products: Accredited status does not imply endorsement by AADE, ANCC, ACPE or CDR of any commercial products displayed in conjunction with this educational activity. Off-Label Use: Participants will be notified by speakers to any product used for a purpose other than that for which it was approved by the Food and Drug Administration. Activity-Type : Knowledge-based or Application based (pick one activity type)

3 1. Compare and contrast the current guideline approaches for the management of type 2 diabetes 2. Describe the pharmacological agents for Type 2 diabetes including long-term safety and efficacy outcomes 3. Construct patient-centered pharmacotherapy plans for patients with type 2 diabetes

4 High prevalence, cost, and mortality! Adapted from: A Snapshot Diabetes in the United States.Infographic.Cdc.gov/diabetes/data/statistics/2014statisticsreport.html.Accessed July 1, 2015

5 Adherence Non-Adherence Education Patient Factors Regimen Changes Medication Factors Communication Provider Factor Good Outcomes Diabetes Educator Poor Outcomes

6 incretin effect pancreatic insulin secretion gut carbohydrate delivery & absorption - HYPERGLYCEMIA? - + hepatic glucose production peripheral glucose uptake Adapted from: Inzucchi SE, Sherwin RS in: Cecil Medicine 2011

7 Diabetes Care 2015;38:

8 Monotherapy Dual Therapy Triple Therapy Entry A1c <7.5% 1.Metformin 2.GLP-1 RA 3.SGLT-2i 4.DPP-4i 5.AGi 6.TZD 7.SU/GLN AGi=alpha glucosidase inhibitor TZD=thiazolidinediones GLN=glitinides Metformin + 1.GLP-1 RA 2.SGLT-2i 3.DPP-4i 4.TZD 5.Basal Insulin 6.Colesevelam 7.Bromocriptine QR 8.AGi 9.SU/GLN Entry A1c >7.5% Progression of Disease Metformin + 2 nd line agent + 1.GLP-1 RA 2.SGLT-2i 3.DPP-4i 4.TZD 5.Basal Insulin 6.Colesevelam 7.Bromocriptine QR 8.AGi 9.SU/GLN

9 American Diabetes Association 2015 Patient-Centered Approach A1c goal < 7% for most patients No preference after Metformin Fewer agents recommended Initial therapy with metformin recommended at diagnosis American Association of Clinical Endocrinologists 2015 Patient-Centered Approach A1c goal 6.5% for most patients Preference given based on safety and efficacy All agents for diabetes included Initial therapy with metformin or dual therapy based on A1c Avoid clinical inertia and both guidelines will lead to similar A1c control

10 Diabetes Care 2015;38: CDEs can impact these factors!

11 S.T.E.P.S. Safety Tolerability What about cardiovascular outcomes? Efficacy Considerations Comorbidities Adverse Effects Pharmacokinetics Costs Price Simplicity

12 The U.S. Food and Drug Administration recommended today that manufacturers developing new drugs and biologics for type 2 diabetes provide evidence that the therapy will not increase the risk of such cardiovascular events as a heart attack. The recommendation is part of a new guidance for industry that applies to all diabetes drugs currently under development. December 17, 2008

13 Relative Risk Diabetic retinopathy Nephropathy Severe nonproliferative or proliferative retinopathy Neuropathy Microalbuminuria Microvascular Outcomes *Based on DCCT data A1C Endocrinol Metab Clin North Am. 1996;25:243

14 S) Risk for lactic acidosis in renal insufficiency Low risk for hypoglycemia T) Nausea and diarrhea common E) High: A1c reduction 1-2% Weight neutral/loss P) Inexpensive: $4.00 or less S) Twice daily Diabetes Care 2015;38:

15 S) May inhibit ischemic preconditioning Moderate risk for hypoglycemia T) Weight gain E) High: A1c reduction 1-2% P) Inexpensive: $4.00 or less S) Once or twice daily Twice daily medications cover post prandial glucose Meglitinides have similar S.T.E.P.S. profile Diabetes Care 2015;38:

16 Lebovitz HE. Diab Rev. 1999;7(3):

17 S) Heart Failure and Bone fractures Liver disease Low risk for hypoglycemia T) Weight gain E) High: A1c reduction 1-2% Insulin sensitizer May take up to 3 months for maximum effects P) Inexpensive S) Once daily Diabetes Care 2015;38:

18 S) Medullary Thyroid Carcinoma (animal studies) Low risk for hypoglycemia T) Nausea/diarrhea E) High: A1c reduction 1-2% Weight loss P) Brand only: Expensive Does this improve adherence??? S) Twice daily, once daily, and once weekly Diabetes Care 2015;38:

19 DPP-4 Inhibitor Rev Diabet Stud, 2008, 5(2):73-94

20 S) Heart failure hospitalizations? Low risk for hypoglycemia T) Rare adverse effects E) Intermediate: A1c reduction 0.5-1% Weight neutral P) Brand only: Expensive S) Once daily Diabetes Care 2015;38:

21 Saxagliptin Risk for Heart Failure Hospitalizations No difference in composite CV death, M.I., or ischemic stroke SAVOR-TIMI 53.Circulation.2014;130: Is this a class effect?

22 Drug DPP-4 Inhibitors Cardiovascular Outcome Trials Trial Rate of HF Hospitalizations Drug vs. Placebo HR 95% CI P-value Alogliptin EXAMINE 3.1% vs. 2.9% 1.07 ( ) Sitagliptin TECOS 3.1% vs. 3.1% 1.00 ( ) 0.98 Saxagliptin Savior_TIMI_53 3.5% vs. 2.8% 1.27 ( ) Risk is not a class effect No other cardiovascular risks, but no improvement in cardiovascular outcomes either SAVOR-TIMI 53.Circulation.2014;130:

23 DPP-4 Inhibitors A1c Reduction (%) Weight Reduction (kg) 100 mg Sitagliptin (-) (-)1.5 5 mg Saxagliptin GLP- 1 Receptor Agonists 10 mcg Exenatide Twice Daily (-1) (-)3.6 2 mg Exenatide Once Weekly (-) (-) mg Liraglutide once daily -1.1-(-) (-) mg Liraglutide once daily -1-(-) (-)3.38 Adapted from: Scheen AJ, et al. Lancet 2010; 375: Weight Loss

24 BH is a 58 yo female with a PMH hypertension, dyslipidemia, and type-2 diabetes is seen for diabetes management. You have optimized her lipid and blood pressure management. Unfortunately, BH s A1c has steadily increased and is now 8.3%. What agent would you add to treat this patient s hyperglycemia? BP: 136/80 mmhg A1c:8.3% BMI:38 kg/m 2 egfr: 71 ml/min/1.73m 2 Microalbumin/Creatinine: 250 mcg/mg Medications: HCTZ 25 mg daily Amlodipine 5 mg daily Rosuvastatin 20 mg daily Aspirin 81 mg daily Metformin 1000 mg BID Lisinopril 20 mg daily A. GLP-1 Agonists C. DPP-4 inhibitor B. Thiazolidinedione D. Sulfonylurea

25 S) Diabetic ketoacidosis? Dehydration Low risk for hypoglycemia T) Genitourinary infections E) Intermediate: A1c reduction 0.5-1% Weight loss P) Brand only: Expensive S) Once daily

26 Diabetes Care.2014;32(1):4-11

27 Primary Outcome: CV death, non-fatal M.I., and non-fatal stroke ARR: 1.6% NNT: 63 N Engl J Med Epub ahead of print. Accessed 11/02/215 Will this be the new 2 nd -line agent in the management of type 2 diabetes?

28 BH is a 58 yo female with a PMH hypertension, dyslipidemia, and type-2 diabetes is seen for diabetes management. You have optimized her lipid and blood pressure management. Unfortunately, BH s A1c has steadily increased and is now 8.3%. What agent would you add to treat this patient s hyperglycemia? BP: 136/80 mmhg A1c:8.3% BMI:38 kg/m 2 egfr: 71 ml/min/1.73m 2 Microalbumin/Creatinine: 250 mcg/mg Medications: HCTZ 25 mg daily Amlodipine 5 mg daily Rosuvastatin 20 mg daily Aspirin 81 mg daily Metformin 1000 mg BID Lisinopril 20 mg daily A. GLP-1 Agonists C. DPP-4 inhibitor B. SGLT-2 Inhibitor D. Sulfonylurea

29 Preferred Glargine (U-100) Detemir NPH Non-Preferred Glargine (U-300) Degludec

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31 % CONTRIBUTION Postprandial Glucose Contribution 100% 80% 60% 70% 50% 45% 40% 30% 40% 20% 0% 50% 55% 60% 70% 30% < >10.2 A1C RANGE (%) PostPrandial Plasma Glucose (PPG) Fasting Plasma Glucose (FPG) Data from Monnier L, et al. Diabetes Care 2003; 26:

32 Holman et al. N Engl J Med 2009; 361:

33 Lowest weight gain and hypoglycemia risk Holman et al. N Engl J Med 2009; 361: Grade 2 = symptoms with SMBG <56 mg/dl; Grade 3 = (major) if third party assistance required

34 NPH Glargine Detemir Glargine Degludec U-100 U-300 U-100 U-200 =2015 Approvals

35 FDA Approval: February 2015 Long acting (up to 36 hours) U-100 U-300: convert 1:1 U-300 U-100: dose reduce by 20% Image source: 11/05/15

36 Outcomes Glargine U-100 Glargine U-300 Less Weight Gain??? Lower Insulin Dose Superior A1c Lowering Lower Hypoglycemia Rates Lower Cost *Generic for glargine U-100 expected this year* Toujeo prescribing information. Accessed 11/02/15 Diab Obes and Met. Edition ;14:

37 Steve-55 y.o. white male PMH: T2DM, HTN, and COPD Medications Lisinopril 20 mg daily Metformin 1000 mg twice daily Insulin glargine: 25 units at bedtime Labs: A1c: 9.4% FBG: 230 mg/dl Scr: 0.9 mg/dl Weight: 250 lbs BMI: 33 What should we do? A. Add an oral agent B. Increase insulin by 4 units C. Add bolus insulin D. Lifestyle modifications only linagliptin 5 mg daily (DPP-4I) Tiotropium 2 puffs daily Blood Glucose Log Pre-Breakfast 200 mg/dl 223 mg/dl 165 mg/dl 179 mg/dl Average 192 mg/dl

38 FDA Approval: September 2015 U-100 and U-200 formulations Biphasic 70/30 with insulin aspart Clin Drug Investig (2013) 33: Similar pharmacokinetic profile

39 Insulin Peak (hours) Duration (hours) NPH Detemir 3-9 hours 6-24 Glargine U-100 No Peak 24 Glargine U-300 No Peak 36 Degludec Degludec? Glargine U-300? Am Fam Physician.2011;84(2):

40 FDA Approval: June 2014 Type 1 and Type 2 diabetes Contraindicated in COPD and Asthma Product Onset (Min) Peak (Min) Duration of Action (hr) Inhaled Insulin ,8, and 12 unit cartridges Small delivery device Insulin naïve patients start at 4 units with meals

41 Hemoglobin A1c Control 8.1 P-VALUE < Baseline 12 weeks 24 weeks Affrezza Placebo Titration occurred over first 12 weeks Diabetes Care Epub ahead of print. Accessed 11/02/15

42 Agent Onset (min) Peak (hrs) Duration (hrs) Aspart Glulisine Lispro U Lispro U <5 Regular Inhaled Rapid (12-15min) 3 Newly approved in 2015 Aspart, Glulisine, and Lispro are interchangeable Increased hypoglycemia associated with regular insulin Pharmacist/Prescriber s Letter :1-12

43 Steve-55 y.o. white male PMH: T2DM, HTN, and COPD Diabetes Medication linagliptin 5 mg daily (DPP-4I) Metformin 1000 mg twice daily Insulin glargine: 36 units at bedtime Labs: A1c: 8.7% FBG: 105 mg/dl Weight: 250 lbs What s the next step? A. Add inhaled insulin B. Add 4 units of lispro to dinner C. Add 4 units of lispro to bedtime D. Increase glargine dose Pre- Breakfast Blood Glucose Log Pre- Lunch Pre- Dinner Bedtime Average Highest Value

44 Use a patient-centered approach when selecting pharmacotherapy agents There is still no 2 nd line agent clearly recommended after metformin therapy Four new insulin products were released in 2015 focusing on concentrated products or new delivery systems The evidence for treatment of type 2 diabetes is rapidly changing

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