ANGELA GINN-MEADOW RD LDN CDE

Transcription

1 DIABETES DRUGS & TRENDS MADE SIMPLE PHARMD TO RD ANGELA GINN-MEADOW RD LDN CDE

2 OBJECTIVES At the end of this presentation, participants should be able to: Evaluate the emerging role of GLP-1 Agonists for weight loss Understand SGLT2 inhibitors in T2DM Explain the role of new insulin therapies in the treatment of Type 2 Diabetes Respond to questions regarding the use of therapies in a specific patients

3 WHAT S HOT AND WHAT S NOT!

4 WHAT S HOT AND WHAT S NOT!

5 GLP-1 R Agonists (DM) Albiglutide (Tanzeum ) Dulaglutide (Trulicity ) GLP-1 R Agonist (Obesity) Liraglutide (Saxenda) DPP-4 Inhibitors Linagliptin (Tradjenta ) Linagliptin/metformin (Jentadueto ) SGLT-2 Inhibitors Empagliflozin (Jardiance ) Empagliflozin/metformin (Synjardy ) SGLT-2 Inhibitors/DPP-4 Inhibitor Empagliflozin/Linagliptin (Glyxambi )

6 Rapid Acting Insulin Lispro (Humalog U-200 Kwikpen ) Long Acting Insulin Degludec (Tresiba ) Insulin Glargine (Toujeo U-300) Insulin Glargine (Basaglar U-100 Kwikpen ) Insulin human injection (Humulin R U-500 Kwikpen ) Inhaled Insulin Insulin human inhalation powder (Afreeza ) Mixed Insulin Insulin Degludec/Insulin Aspart (Ryzodeg 70/30 )

7 GLP-1 RECEPTOR AGONIST: LIRAGLUTIDE (SAXENDA ) - OBESITY

8 GLP-1 MODULATES NUMEROUS FUNCTIONS IN HUMANS GLP-1: Secreted upon the ingestion of food Promotes satiety and reduces appetite Alpha cells: Glucose-dependent postprandial glucagon secretion Beta cells: Enhances glucose-dependent insulin secretion Liver: Glucagon reduces hepatic glucose output Stomach: Helps regulate gastric emptying Data from Flint A, et al. J Clin Invest. 1998;101: ; Data from Larsson H, et al. Acta Physiol Scand. 1997;160: Data from Nauck MA, et al. Diabetologia. 1996;39: ; Data from Drucker DJ. Diabetes. 1998;47:

9 LIRAGLUTIDE (SAXENDA ) A GLP-1-R AGONIST WITH NEW INDICATION - WEIGHT LOSS

10 LIRAGLUTIDE (SAXENDA ) - OBESITY Indication: Adjunct to lifestyle (reduced calorie diet and increased physical activity) for chronic weight management In individuals with a BMI of >30 kg/m 2 In individuals with a BMI of >27 kg/m 2 in the presence of at least one weight-related comorbidity such as HTN, Diabetes, or Dyslipidemia Saxenda prescribing information: Accessed 2/26/16

11 SAXENDA SAFETY AND EFFICACY CLINICAL TRIALS Three 56-week, randomized, double-blind, placebo-controlled trials All patients were overweight ( kg/m 2 ) or obese >30 kg/m 2 Dosage titration: to 3 mg daily during a 4-week period All patients received instructions throughout the trial for: A reduced calorie diet (approximately 500 kcal/day deficit) Exercise counseling - minimum 150 mins/week)

12 RESULTS OF THE CLINICAL TRIAL Baseline mean (SD) (kg) Study 1 (Obesity/overweight + comorbidity) Saxenda N= (21.2) Placebo N= (21.7) Study 2 (Obesity/overweight + Type 2 DM) Saxenda N= (21.9) Placebo N= (21.3) Study 3 (Obesity or overweight + comorbidity following > 5% weight loss with diet) Saxenda Placebo N=212 N= (20.8) 98.7 (21.2) % change from baseline (LSMean) Difference from placebo (LSMean) (95% CI) -4.5* (-5.2;-3.8) -3.7* (-4.7;-2.7) -5.2* (-6.8;-3.5) % Patients losing > 5% BW 62.3% 34.4% 49.0% 16.4% 44.2% 21.7% Difference from placebo (LSMean) (95% CI) 27.9* (23.9;31.9 ) 32.6* (25.1;40.1) 22.6* (13.9;31.3) % Patients losing >10% BW 33.9% 15.4% 22.4% 5.5% 25.4% 6.9% Difference from placebo (LSMean) (95% CI) 18.5* (15.2;21.7 ) 16.9* (11.7;22.1) 18.5* (11.7;25.3)

13 RESULTS OF STUDY ONE Saxenda reduced waist circumference by 3.2 inches vs 1.6 inches with placebo

14 SAXENDA AND SUSTAINED WEIGHT LOSS

15 LIRAGLUTIDE (SAXENDA ) Do not use Saxenda : To treat Type 2 diabetes With Victoza or other GLP-1 receptor agonists Together with insulin There is no safety data on Saxenda use: With other prescription, over-the-counter, or herbal weight-loss products In people who have had pancreatitis In children <18 years of age. Saxenda Is Not For Use In Children

16 DOSAGE FOR SAXENDA VS. VICTOZA SAXENDA FOR WEIGHT LOSS VICTOZA FOR T2DM Dose of Saxenda mg daily for weight loss Evaluate patients after 16 weeks If patient has not lost 4% of baseline body weight, discontinue therapy Dose of Victoza mg or 1.8 mg daily for diabetes

17 QUESTION ON LIRAGLUTIDE (SAXENDA ) Which of the following patients with BMI of > 27 kg/m 2 will be eligible for Saxenda? All patients have HTN and Dyslipidemia PINK T1 DM Patient on Insulin Glargine + Insulin Aspart BLUE T1 DM Patient on 70/30 Insulin GREEN T2 DM Patient on Metformin YELLOW T2 DM Patient on Exenatide

18 SGLT-2 INHIBITORS AND ITS COMBINATIONS SGLT-2 Inhibitors Empagliflozin (Jardiance ) Empagliflozin/metformin (Synjardy ) SGLT-2 Inhibitors/DPP-4 Inhibitor Empagliflozin/Linagliptin (Glyxambi )

19 SODIUM-GLUCOSE COTRANSPORTER-2 INHIBITORS: GLUCOSE TRANSPORTATION AT THE KIDNEYS Wright, EM. Am J Renal Physiol 2001;280(1):F10 - F18 Taylor SR, Harris KB. Pharmacotherapy 2013; 33(9):

20 EMPA-REG OUTCOME STUDY Aim: To determine the long-term CV safety of Empagliflozin Inclusion: >7000 drug-naïve patients (HbA 1c 7.0% and 9.0%), or on glucose-lowering therapy (HbA 1c 7.0% and 10.0%)at high risk for CV events Treatment: Randomized (1:1:1) and treated with Empagliflozin 10 mg, 25 mg, or placebo Primary outcome: Time to first occurrence of CV death, non-fatal myocardial infarction, or nonfatal stroke Zinman B, et al. N Engl J Med 2015;373(22):

21 EMPAGLIFLOZIN MODULATES SEVERAL FACTORS RELATED TO CV RISK 21 BP Arterial stiffness Other Albuminuria Sympathetic nervous system activity Glucose Insulin Uric acid Weight Visceral adiposity Oxidative stress LDL-C HDL-C Triglycerides Adapted from Inzucchi SE,Zinman, B, Wanner, C et al. Diab Vasc Dis Res 2015;12:90-100

22 22 EMPA-REG OUTCOME : SUMMARY Empagliflozin reduced HF hospitalization by 35% Empagliflozin reduced CV death by 38% Empagliflozin improved survival by reducing all-cause mortality by 32%

23 NUMBER NEEDED TO TREAT (NNT) TO PREVENT ONE DEATH ACROSS LANDMARK TRIALS IN PATIENTS WITH HIGH CV RISK 23 Simvastatin 1 for 5.4 years Ramipril 2 for 5 years Empagliflozin for 3 years High CV risk 5% diabetes, 26% hypertension Pre-statin era High CV risk 38% diabetes, 46% hypertension Pre-ACEi/ARB era <29% statin T2DM with high CV risk 92% hypertension >80% ACEi/ARB >75% statin S investigator. Lancet 1994; 344: , HOPE investigator N Engl J Med 2000;342:145-53, HOPE.htm

24 EMPAGLIFLOZIN/LINAGLIPTIN (GLYXAMBI ) OBJECTIVE To evaluate the efficacy and safety of empagliflozin/linagliptin as second-line therapy in subjects with T2DM inadequately controlled on metformin RESEARCH DESIGN : Subjects were randomized to a combination of 1. Empagliflozin 25 mg/linagliptin 5 mg (n = 137) 2. Empagliflozin 10 mg/linagliptin 5 mg (n = 136) 3. Empagliflozin 25 mg (n = 141) 4. Empagliflozin 10 mg (n = 140) 5. Linagliptin 5 mg (n = 132) as add-on to metformin for 52 weeks DeFronzo RA, Lewin A, Patel S, et al. Combination of empagliflozin and linagliptin as second-line therapy in subjects with type 2 diabetes inadequately controlled on metformin. Diabetes Care. 2015;38(3):

25 RESULTS OF THE STUDY

26 QUESTION ON EMPAREG STUDY The EmpaREg Study demonstrated positive outcomes in all of the following CV outcomes, EXCEPT: RED BLUE GREEN YELLOW Myocardial Infarction; Stroke Heart Failure Hospitalization Cardiovascular Death All Cause Mortality

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29 BIOEQUIVALENCE: HUMALOG U 200 VS 100 SAME DOSE; ½ THE VOLUME

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31 INSULIN GLARGINE U-300 (TOUJEO ) NONBIOEQUIVALENT TO GLARGINE U-100 Noninferior: similar A1c lowering More basal insulin use of Toujeo in both T1 and T2DM Rates of hypoglycemia? For patients controlled on insulin glargine U100, a higher daily dose of TOUJEO will be needed From twice-daily NPH insulin to once-daily TOUJEO, the recommended starting TOUJEO dose is 80% of the total daily NPH dosage

32 HUMULIN R U-500 KWIKPEN Available in April 2016 Onset of Action = within 30 min Duration of Action = 1 hour Pen: No Dose Conversion compared to Vial

33 POTENTIAL CANDIDATES FOR U-500 HUMAN REGULAR INSULIN T2DM Patients with obesity/severe insulin resistance Patients requiring >200 units of insulin per day High glucocorticoid therapy Severe systemic infection Gestational diabetes with severe insulin resistance Genetic defects of insulin action Type A insulin resistance syndromes Immune mediated diabetes (anti-insulin receptor antibodies)

34 INSULIN DEGLUDEC (TRESIBA ) U- 200 AND U-100 FLEXTOUCH

35 INSULIN DEGLUDEC (TRESIBA ): BEGIN STUDIES Ultra long acting insulin (dosed daily) Onset of Action: minutes Its duration of action is up to 42 hours compared to 18 to 26 hours (glargine and insulin detemir) Efficacy: Non inferior to Lantus (glargine) Benefit: Flexibility in day to day dosing time Gough SCL, Harris S, Woo V, et al. Insulin degludec: overview of a novel ultra longacting basal insulin. Diabetes, Obesity and Metabolism (15): 301 9

36 TRESIBA DOSING NO dose conversion between TRESIBA U-100 or U-200 FlexTouch pens The dose window for both FlexTouch pens shows the number of insulin units to be delivered Starting Dose in Insulin Naïve T1DM Patients in insulin naïve patients with type 1 diabetes is ~ 1/3 to ½ of TDD Starting dose in insulin naïve T2DM patients is 10 units once daily

37 QUESTION ON INSULIN Which of the following insulin(s) is/are bioequivalent (require no dose conversion)? RED BLUE Toujeo (Glargine) U-300 vs. Lantus (Glargine) U-100 Humalog Kwikpen U-200 vs. Humalog Kwikpen U-100 GREEN Humulin R Kwikpen U-500 vs. Humulin R U-100 YELLOW Tresiba (Insulin Degludec) U-200 vs. Tresiba U-100

38 MINI-CASE PATIENT AB Chief complaint: I want to lose weight HPI: 52-year-old woman with Type 2 DM, HTN Vitals: Weight: 220 lb; Height 5 4 ; BMI 37.8 Labs: HbA1c 8.8% Diet: None Medications Metformin (Glucophage XR) 1,000 mg bid Empagliflozin (Jardiance ) 25 mg daily Liraglutide (Victoza ) 1.8 mg daily HCTZ 25 mg once daily 46

39 QUESTION ON PATIENT - AB Is this patient, AB a candidate for Saxenda? RED BLUE Saxenda (Liraglutide) is safe Use if you discontinue her Glucophage (Metformin) GREEN Use if you discontinue her Victoza (Liraglutide) YELLOW Use if you discontinue her Jardiance (Empagliflozin)

40 KEY TAKE AWAY POINTS Clinical trials show 62% and 34% of patients on Saxenda (Liraglutide) 3 mg, decrease weight by 5% and 10% respectively from baseline Empagliflozin demonstrated positive CV outcomes in decreasing HF hospitalizations; CV death and all cause mortality (not MI or Stroke) PK/PD studies must demonstrate bioequivalence in order to maintain dosing in concentrated insulin with their U-100 counterparts Concentrated insulin has the same dose but less volume

41 QUESTION FOR AUDIENCE On completion of this presentation, RED I learnt at least one important fact today BLUE I am still muddy about one point GREEN I need one area clarified today YELLOW I slept through, so I have no questions

42 THANKS! Any questions? You can me at