Next Generation Diabetes Management:

Transcription

1 Next Generation Diabetes Management: Titratable Fixed-Ratio Combination Therapy with Basal Insulin/GLP-1 RA to Better Manage Type 2 Diabetes Supported by an educational grant from Sanofi US Learning Objectives Compare and contrast current guidelines/recommendations for patients with type 2 diabetes mellitus (T2DM) not at goal Review data on combination GLP-1 RAs and basal insulin for individuals with T2DM when intensification is needed Identify how fixed-dose combination therapy with GLP1-RA and insulin can help patients achieve glycemic goals Formulate strategies to overcome barriers to the introduction and intensification of fixed ratio therapies 2 1

2 CURRENT STATE OF GLYCEMIC CONTROL AND REVIEW OF UPDATED T2D GUIDELINES 3 T2D: A Global Epidemic T2D global prevalence = million people o 30.3 million people have diabetes / 9.4% of the US population (2017) o 7th leading cause of death in the US o Projected to be million in the year 2045 Considerable economic cost: Total US diabetes healthcare expenditures = $727 billion (2017) Complications of T2DM can be delayed and possibly avoided with timely and aggressive treatment with lifestyle modification, medication, and follow-up Accessed

3 Current Recommendations AACE ADA A1C (%) Pre-prandial mg/dl < Peak postprandial mg/dl <140 <180 Endocr Pract.2018,doi: /CS Diabetes Care Volume 41, Supplement 1, January Reprinted with permission from American Association of Clinical Endocrinologists 2018 AACE. Garber AJ, Abrahamson MJ, Barzilay JI, et al. AACE/ACE comprehensive type 2 diabetes management algorithm Endocr Pract.2018;24:

4 Reprinted with permission from American Association of Clinical Endocrinologists 2018 AACE. Garber AJ, Abrahamson MJ, Barzilay JI, et al. AACE/ACE comprehensive type 2 diabetes management algorithm Endocr Pract.2018;24: Combination Injectable Therapy for T2D American Diabetes8. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes Copyright and all rights reserved. Material from this publication has been used with the permission of American Diabetes Association. 8 4

5 In Your Practice Do you follow AACE/ACE guidelines? Do you follow ADA guidelines? Do you follow another protocol? 9 Clinical Case

6 64 year old Male with T2DM Medical history MI/CABG x Stent x Diabetes dx 2008 Hypertension well controlled on medication Hyperlipidemia well controlled on medication November 2017 Visit A1C 12.9% Quit his GLP1 RA 4 months ago (A1C was 7.8% at that time) Not feeling well lately and very surprised at his lab results today Restarted his GLP1 RA after today s visit June 2018 Visit A1C 9% 6 months later his A1C is down and he is still taking his GLP1 RA. Not at goal 11 Rationale for a Fixed-Ratio Combination How could a GLP-1 RA and Basal Insulin help Mark get to goal?

7 Incretin Response to Insulin Secretion Control subjects (n=8) Persons with T2D (n=14) Insulin (mu/l) Springer Nature Incretin effect Insulin (mu/l) Time (min) Time (min) 180 Oral glucose load Intravenous glucose infusion Adapted by permission from Springer-Verlag: Springer Nature Diabetologia. Reduced incretin effect in Type 2 (non-insulin-dependent) diabetes, M. Nauck, F. StOckmann, R. Ebert and W. Creutzfeldt, COPYRIGHT (1986) 13 Physiologic Effect of Glucagon-Like Peptides (GLP) Promotes satiety & reduces appetite Glucagon reduces hepatic glucose output Slows gastric emptying Alpha cells: Postprandial glucagon secretion GLP1 secreted when food ingested Beta cells: Glucose-dependent insulin secretion

8 GLP-1 RA + Basal Insulin: Rationale Characteristic GLP-1 RA Basal Insulin MOA (Mechanism of Action) Glucose profile glucose-dependent pancreatic insulin secretion glucose-dependent glucagon secretion gastric emptying satiety/ appetite Short-acting agents: PPG excursions Long-acting agents: PPG + FPG A1C % Mimics basal rate of endogenous insulin glucose disposal hepatic glucose production FPG Body weight Weight Weight Effect on pancreatic ß cells May improve ß cell function Rests ß cells glucose toxicity Anderson SL, Trujillo JM. Diabetes Spectrum. 2016; 29: Vedtofte L, et al. Exper Rev Clin Pharmacol. 2015;8: GLP-1 RA + Basal Insulin (cont.) Characteristic GLP-1 RA Basal Insulin Contraindications egfr<30 (exenatide) Gastroparesis, pancreatitis, acute gall bladder disease Black box: contraindicated with personal/family history MTC* or MEN2 # (except exenatide) Side Effects Nausea Diarrhea Vomiting Hypoglycemia Weight gain *MTC :Meducillary thyroid carcinoma; # MEN2: Multiple endocrine neoplasia type 2 Anderson SL, Trujillo JM. Diabetes Spectrum. 2016; 29: Vedtofte L, et al. Exper Rev Clin Pharmacol. 2015;8:

9 GLP-1 RA + Basal Insulin Fixed-dose Combination Agents IDegLira (Xultophy) Insulin degludec (100 U/mL) Liraglutide (3.6 mg/l) LixiLan (Soliqua) Insulin glargine (100 U/mL) Lixisenatide (33 mcg/ml) 17 GLP-1 RAs in Fixed-dose Combinations Property Liraglutide Lixisenatide Half-life, hours A1C change, % 0.6 to 0.9* 0.7 to 0.9 Body weight change, kg 1.8 to to 3.8 Nausea, % of patients 11.3 to to 43.5 Hypoglycemia, % of patients 4.1 to to 7.2 *Degree of change depended on study design and dose (1.2 or 1.8 mg) Courtney H, et al. Diab Metabolic Synd Obes: Targets Ther. 2017;10:

10 Combined Insulin and GLP-1 RA: IDegLira vs Max Liraglutide or Exenatide Change in A1C (%) Change in BWt (kg) Linjawi, S., Bode, B.W., Chaykin, L.B. et al. Diabetes Ther (2017) 8: Combined Insulin + GLP-1 RA: IDegLira vs Insulin Glargine up-titration Insulin glargine Insulin degludec/liraglutide Reproduced with permission from JAMA (9): Copyright (2016) American Medical Association. All rights reserved

11 Combined Insulin and GLP-1 RA: LixiLan American Diabetes Association Benefits of LixiLan, a Titratable Fixed-Ratio Combination of Insulin Glargine Plus Lixisenatide, Versus Insulin Glargine and Lixisenatide Monocomponents in Type 2 Diabetes Inadequately Controlled on Oral Agents: The LixiLan-O Randomized Trial, Copyright and all rights reserved. Material from this publication has been used with the permission of American Diabetes Association 23 Practical Considerations in Patient Selection

12 Using Combination Basal Insulin/GLP-1 RA Name Strength Indication/Dosing Degludec/liraglutide combination (Xultophy ) Glargine/lixisenatide combination (Soliqua ) 100/3.6 Maximum daily dose 50 units 100 /33 Maximum daily dose 60 units For use if basal insulin <50 units daily or liraglutide < 1.8mg daily Administered daily/ same time Starting dose 16 units/0.58 mg (each 1 unit increment=0.4 mg) Administer daily 1 hour before 1 st meal of day Starting dose 15 units/5 mg if taking glargine <30 units (1unit= 0.4 mg) Starting dose 30 units/10 mg if taking units of glargine 23 Degludec/Liraglutide (Xultophy ) Xultophy Degludec Liraglutide Xultophy Degludec Liraglutide units 0.58 mcg units 1.22 mcg units 0.65 mcg units 1.3 mcg units 0.72 mcg units 1.37 mcg units 0.79 mcg units 1.44 mcg units 0.86 mcg units 1.51 mcg units 0.94 mcg units 1.66 mcg units 1.01 mcg units 16.7 mcg units 1.08 mcg units 1.73 mcg units 1.15 mcg units 1.8 mcg

13 Glargine/Lixisenatide (Soliqua ) Soliqua Lantus Lixisenatide Soliqua Lantus Lixisenatide units 5 mcg units 12.7 mcg units 6 mcg units 13.3 mcg units 6.7 mcg units 14 mcg units 7.3 mcg units 14.7 mcg units 8 mcg units 15.3 mcg units 8.7 mcg units 16 mcg units 9.3 mcg units 16.7 mcg units 10 mcg units 17.3 mcg units 10.7 mcg units 18 mcg units 11.3 mcg units 18.7 mcg units 12 mcg units 20 mcg 25 Dose Adjustment: Degludec/Liraglutide (Xultophy ) and Glargine/Lixisenatide (Soliqua )

14 Instruct on Needle Size and Safety Demonstrate pen use with a demo, OR Take first injection in the office Site preparation and rotation Unopened and opened storage recommendations Safely disposal of needles Image by BruceBlaus [CC BY-SA 4.0 ( from Wikimedia Squares 27 Individualizing a T2D Management Approach A Age E Expense/life expectancy B Body weight Blood pressure management F Feelings/attitudes C Complications G Glycemic targets D Duration of diabetes/ Determine treatment goals H Hypo/Hyperglycemic concerns Adapted from:

15 Patient-Centered Communication Recommendations Use personcentered; focus on patient strengths Elicits patient preferences and beliefs Uses active listening skills Assesses literacy, numeracy, and potential barriers to care Optimizes patient health outcomes and health-related quality of life Comprehensive Medical Evaluation and Assessment of Comorbidities: Standards of Medical Care in Diabetes Diabetes Care 2018; 41 (Suppl. 1): S28-S CASE STUDY MARK Medical history Age 52 BMI 32, wt. 208 lbs. BP 134/70 A1c 9% Medications: Injecting liraglutide 1.8 mg daily Metformin 500mg XR 2 tabs daily in evening Atorvastatin 40mg daily Lisinopril 20mg daily Daily Glucose Log Day of the Week Fasting Dinner Monday 287 Tuesday Wednesday Thursday 212 Friday Saturday 233 Treatment Plan To continue metformin Stop liraglutide 1.8 mg daily To start fixed ratio combination injection at starting dose To increase dose by 4 units every week until average fasting less than

16 Formulating Strategies to Overcome Barriers to Introduction and Intensification of Fixed-Ratio Therapies 31 Common Nurse Practitioner (NP) Barriers to Treatment Intensification Uncertainty about A1C goals and guidelines Lack of training about how to intensify antihyperglycemic therapy Unawareness of new treatment/medication options Time constraints Lack of care coordination Patient motivation, including fears and concerns with dosing regimen Blonde, 2017, Quality in Primary Care (2017) 25 (3):

17 Strategies to Guide T2D Improvements Treatment Intensification: From the NP Perspective Refer Develop Utilize Solicit Feedback Follow up As appropriate to other healthcare disciplines- diabetes educators, specialists Non-judgmental approach- avoiding blame and shame Available patient education resources- AANP, ADA, AADE Elicit patient feedback, be open minded Regular follow- up appointments- longer time & shorter intervals Com prehensive MedicalEvaluation and Assessm entof Com orbidities:standards of Medical Care in Diabetes Diabetes Care 2018;41 (Suppl.1):S28-S37 Prioritize Prioritize goals & set realistic goals 33 Strategies to Help Overcome Patient Barriers to Treatment Determine Barriers Needle size/fear of injections? Dose complexity, need for mixing solutions, cumbersome devices (vial and syringe)? Misconceptions/myths? Fear of medication classes? Side effect concerns: weight gain, hypoglycemia? Highlight Solutions Smaller needle size options Ease of therapy Dose simplicity Weight loss Reduced hunger Glycemic stability Comprehensive Medical Evaluation and Assessment of Comorbidities: Standards of Medical Care in Diabetes Diabetes Care 2018; 41 (Suppl. 1): S28-S

18 CASE STUDY MARK Age 52 BMI 31, wt. 206 BP 127/84 Current A1c 7.2% Medical history Medications: Fixed ratio combination injection 28 units daily Metformin 500mg XR 2 tabs daily Atorvastatin 40mg daily Lisinopril 20mg daily Daily Glucose Log Day of the Week Fasting Dinner Monday Tuesday Wednesday Thursday Forgot to test Friday Saturday 142 No test Treatment Plan No side effects or hypoglycemia Average fasting 108 at 28 units of fixed ratio combination Encouraged continue weight loss and lifestyle 35 Conclusion Effective management of diabetes is a multifaceted and includes an individualized treatment regimen based on attributes from the acronym A- H (age, body weight, complications, duration of diabetes, etc.) Fixed- dose combination therapy targets multiple pathophysiological defects in Type 2 diabetes while conferring improved glucose control with low risk for hypoglycemia Less complex treatment regimens such as fixed-dose combinations promote greater patient adherence A patient centered approach with shared decision can help address the patient barriers to intensification along with proper patient education & resources

19 RESOURCES 37 Degludec/Liraglutide (Xultophy ) Xultophy Degludec Liraglutide Xultophy Degludec Liraglutide units 0.58 mcg units 1.22 mcg units 0.65 mcg units 1.3 mcg units 0.72 mcg units 1.37 mcg units 0.79 mcg units 1.44 mcg units 0.86 mcg units 1.51 mcg units 0.94 mcg units 1.66 mcg units 1.01 mcg units 16.7 mcg units 1.08 mcg units 1.73 mcg units 1.15 mcg units 1.8 mcg

20 Glargine/Lixisenatide (Soliqua ) Soliqua Lantus Lixisenatide Soliqua Lantus Lixisenatide units 5 mcg units 12.7 mcg units 6 mcg units 13.3 mcg units 6.7 mcg units 14 mcg units 7.3 mcg units 14.7 mcg units 8 mcg units 15.3 mcg units 8.7 mcg units 16 mcg units 9.3 mcg units 16.7 mcg units 10 mcg units 17.3 mcg units 10.7 mcg units 18 mcg units 11.3 mcg units 18.7 mcg units 12 mcg units 20 mcg 39 PATIENT HANDOUT 40 20

21 Type of Drug and How It Works INSULIN/GLP-1 RA COMBINATION MEDICATION Generic Name Brand Name Risk of Hypoglycemia GLP-1 Receptor Agonists (RA)/Basal Insulin Combination What You Should Know Before Choosing This Medication The GLP-1 RA: Helps your pancreas make more insulin in response to eating. Prevents your liver from making extra glucose (sugar) overnight and between meals. Slows the rate of food emptying from your stomach. Helps you feel full after eating. The basal insulin: Gives your body extra insulin to control blood glucose (BG) between meals and overnight. Degludec/liraglutide Glargine/lixisenatide Weight Change Xultophy 100/3.6 Soliqua 100/33 This medication may help prevent weight gain and might help with weight loss. Low to medium A1C Change 1-2% These medications are taken by injection (shot). They are a combination of a long-acting basal insulin and a GLP-1 RA. Together, they help control your BG between meals and overnight (basal insulin) and prevent your BG from rising after meals (GLP-1 RA). Side effects: Nausea which usually lessens after you take the medication for a while. Hypoglycemia (low blood sugar) can occur when you take any insulin. Possible risks: May increase the risk of pancreatitis (inflammation of the pancreas). Adjusting Dose Storage How It Is Taken Tips for Administration If Fasting Blood Glucose (FBG) is above Increase dose by units (Increase up to four units at a time) If FBG is at target Make no change If FBG is below Decrease dose by units Until FBG is at (Fasting = at least 6-8 hours without food) Opened: Xultophy can be stored at room temperature for up to 21 days after opening Soliqua can be stored at room temperature for up to 14 days after opening Unopened: Store in refrigerator until expiration date Xultophy : Inject once a day at the same time each day Soliqua : Inject once a day within one hour of your first meal You will need two prescriptions: one for the pen and one for the pen needles (recommended needle size is 4-5 millimeters). Injection sites include the abdomen (belly), back of arms and upper or outer thigh. You should rotate the injection to a different site each time you give yourself a shot. You should prime the pen (air shot) before each dose with 1-2 units to clear the needle of air. Please see package instructions for details. After injecting but before removing the needle, you should count to 10 to make sure you get your full dose of medication AANP

22 INSULIN/GLP-1 RA COMBINATION MEDICATION My A1C My Blood Glucose When Should I Check My Blood Sugar? My A1C now is: The A1C goal is: My FBG target is: My target before a meal is: My target after a meal is: My target at bedtime is: Before: Breakfast Lunch Dinner 1-2 hours after: Breakfast Lunch Dinner At: Bedtime Comments: My Next Appointment My Current Medications for Diabetes: Recommended Time of Day to Take Medications: Date: Bring your glucose meter Bring your glucose log Bring your medications 1) 1) 2) 2) 3) 3) 4) 4) If you are unable to fill your prescription or cannot take the medication, contact the office or call. If my blood glucose gets too low (hypoglycemia) (below ), I should take 1 of the items below and recheck my blood sugar every 15 minutes until my blood glucose level is above : 4 glucose tablets ½ cup fruit juice ½ cup of regular (not diet) soft drink 1 cup of nonfat or 1% milk 1 tablespoon of sugar or honey Other: NOTES: By BruceBlaus [CC BY-SA 4.0 ( from Wikimedia Squares Supported by an educational grant from Sanofi US 2018 AANP