A Practical Approach to the Use of Diabetes Medications

Transcription

1 A Practical Approach to the Use of Diabetes Medications Juan Pablo Frias, M.D., FACE President, National Research Institute, Los Angles, CA Clinical Faculty, University of California, San Diego, CA

2 OUTLINE Pathophysiology of Type 2 Diabetes Natural history of Type 2 Diabetes Type 2 Diabetes Management Guidelines FDA-approved Therapeutic Options Case Studies

3 Pathophysiology of Type 2 Diabetes

4 Natural History of Type 2 Diabetes

5 Diabetes Drug Classes Increasing Rapidly

6 Type 2 Diabetes Therapy: Sites of Action

7 Key ADA Publications ADA = American Diabetes Association American Diabetes Association. Diabetes Care 2013:36(Suppl 1):S Inzucchi SE, et al. Diabetes Care 2012;35:

8 Managing Glucose in Type 2 Diabetes

9 Managing Glucose in Type 2 Diabetes

10 Managing Glucose in Type 2 Diabetes

11 General Glycemic Targets Measure ADA AACE A1C <7.0% 6.5% Preprandial capillary plasma glucose Postprandial capillary plasma glucose mg/dl <110 mg/dl <180 mg/dl <140 mg/dl American Diabetes Association. Diabetes Care 2013:36(Suppl 1):S Garber AJ, et al. Endocrine Practice. 2013;19(Suppl 2):1-38.

12 Glycemic Targets Should be Individualized Inzucchi SE, et al. Diabetes Care 2012;35:

13 Metformin

14 Insulin Secretagogues

15 Secondary Failure Rate with SFU

16 Glitazones

17 Glucoregulatory Effects of GLP-1

18 GLP-1 is Rapidly Degraded by DPP-4

19 Strategies for Enhancing GLP-1 Action Dipeptidyl Peptidase-4 (DPP-4) Inhibitors Inhibit the actions of DPP-4 FDA approved: sitagliptin, saxagliptin, linagliptin, alogliptin GLP-1 Receptor Agonists Resistant to DPP-4 inactivation Activators/agonists of the GLP-1 receptor FDA approved: exenatide, liraglutide, exenatide extended-release Drucker DJ, et al., Diabetes Care 2010;33(2):

20 DPP-4 Inhibitors

21 DPP-4 Inhibitors

22 GLP-1 Receptor Agonists

23 GLP-1 Receptor Agonists

24 SGLT2 Inhibitors

25 Renal Handling of Glucose in a Non-Diabetic Individual

26 Renal Glucose Reabsorption is Increased in Type 2 Diabetes

27 Idealized Profiles of Human Insulin and Insulin Analogs

28 Insulin Delivery Devices

29 V-Go Disposable Insulin Delivery Devices

30 Complimentary Features of Basal Insulin and Incretin-based Therapy

31 CASE STUDIES

32 Case #1 58 year old obese Asian American male Type 2 diabetes diagnosed 5 years ago Taking metformin (2,000 mg/day); A1C=7.7% Family History: Type 2 diabetes and obesity (both parents) Notes: - Very fearful of injections and gaining weight - BMI 31kg/m 2

33 Case #1-Q1 How would you treat this patient to lower his A1C? A B C D E Add a SFU Add a TZD Start a SGLT-2 inhibitor Add a GLP-1 receptor agonist (exenatide or liraglutide) Add a DPP-4 inhibitor

34 Case #2 54 year old obese African American female Type 2 diabetes for 7 years On maximum dose of a SFU and DPP-4 inhibitor Long-standing difficult to control hypertension, mild CHF and mild renal insufficiency Labs - A1C: 7.6% (goal <7.0%) - LDL-C: 121 mg/dl - TG: 176 mg/dl - LFTs and TSH: Normal

35 Case #2-Q2 What medication(s) would be appropriate to initiate for at this time? A B C D Metformin TZD (pioglitazone or rosiglitazone) Bile acid sequestrant (colesevelam) SGLT-2 inhibitor (cana-, dapagliflozin)

36 Case #3 55 year-old Latino female Type 2 diabetes diagnosed 8 years ago PMH: HTN, dyslipidemia, sleep apnea and osteoporosis Social History: Housewife, has health insurance through husband s work, smokes ½ pack per day Complains of always being tired Medications: Metformin 1000 mg BID and glipizide 20 mg QD (regimen for 2 yrs) HCTZ 25 mg QD, lisinopril 20 mg QD, atorvastatin 20 mg QD

37 Case #3 Height 5 4 ; weight 198 lbs (BMI= 34 kg/m 2 ) BP=128/74 A1C=9.1% (goal <7.0%; 4 months ago 8.6%) Total cholesterol=194 mg/dl; LDL-C=120 mg/dl, HDL-C=42 mg/dl, TG=162 mg/dl Normal renal function

38 Case #3

39 Case #3-Q3 How would you treat Maria to lower her A1C? A B C D E F Add pioglitazone Nutrition and exercise counseling only Add a DPP-4 inhibitor Add basal insulin Add a SGLT2 inhibitor Add a GLP-1 receptor agonist

40 Case #3-Q4 What else would you consider during Maria s visit? A B Discuss medication adherence Check a TSH C. Counsel about smoking cessation D E F Consider aspirin therapy Consider increasing atorvastatin dose All of the above

41 Case #3 Insulin glargine initiated at 20 U every evening Metformin and glipizide continued at same doses Given instructions to titrate glargine by 2 U every 3 days until FPG in mg/dl range TSH was normal and atorvastatin increased to 40 mg daily Initiated daily baby ASA and referred to smoking cessation counseling

42 Case #3 Returns to your office in 2.5 months Insulin glargine 58 U QHS No hypoglycemia A1C = 7.8%; Fasting glucose ~110 mg/dl Has gained 6 lbs

43 Case #3

44 Case #3-Q5 Maria s A1C is 7.8% and FPG is at goal. What would you do next to improve her glycemic control? A B C D E Add a DPP-4 inhibitor Increase glipizide dose Add a GLP-1 receptor agonist Add prandial insulin at breakfast Add a SGLT2 inhibitor

45 Case #3 Initiated liraglutide at 0.6 mg QD and increased over 4 weeks to 1.8 mg QD Mild nausea (no vomiting) during first 2 weeks which subsided Glipizide discontinued and insulin dose reduced by ~20% upon initiation of GLP-1 RA Clinical Pearl: With high post-dinner and bedtime glucose and near-normal fasting glucose, if basal insulin not reduced, improving post-dinner and bedtime glucose with GLP-1 RA could result in nocturnal hypoglycemia.

46 Case #3 A1C 1.1% (to 6.7%) and body weight ~8 lbs over the next 3-4 months A1C stable over a 9 month period on metformin 1000 mg BID, liraglutide 1.8 mg QD and insulin glargine 52 U QHS

47 KEY TAKEAWAYS Glycemic targets & glucose-lowering therapies should be individualized Diet, exercise and education are the foundations of therapy Unless contraindicated, metformin is optimal 1st-line drug After metformin, combination therapy with 1-2 other oral and/or injectable agents; minimize side effects Ultimately, many patients will require insulin therapy alone or in combination with other agents to maintain glycemic control All treatment decisions should be made in conjunction with the patient (focus on preferences, needs and values) Comprehensive CV risk reduction is a major focus of therapy

48 Thank you very much! Juan P. Frias, MD