Diabetes: When To Treat With Insulin and Treatment Goals

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1 Diabetes: When To Treat With Insulin and Treatment Goals Lanita. S. White, Pharm.D. Director, UAMS 12 th Street Health and Wellness Center Assistant Professor of Pharmacy Practice, UAMS College of Pharmacy

2 Disclosures I have no affiliation or financial disclosures.

3 Objectives Define types of insulin and their actions. Determine when insulin should be initiated or when insulin doses should be titrated in patients with type 2 diabetes. Identify goals of therapy and assessment methods once insulin is initiated in patients with type 2 diabetes. Create appropriate insulin regimens based on provided patient cases in patients with type 2 diabetes.

4 INSULINS

5 Rapid Acting - lispro (Humalog ) - glulisine (Apidra ) - aspart (Novolog ) Type Onset Peak Effective Duration 5-15 min min < 5 hours Short Acting - Regular Insulin (Novolin R / ReliOn R) (Humulin R) Intermediate Acting - neutral protamine hagedorn (NPH) (Novolin N / ReliOn N) (Humulin N) Long Acting - glargine (Lantus ) - detemir (Levemir ) min 2 3 hours 5 8 hours 2 4 hours 4 10 hours hours 2 4 hours 1 3 hours No peak Relatively flat hours 24 hours

protamine hagedorn (NPH) (Novolin N / ReliOn N) (Humulin N) Long Acting - glargine (Lantus ) - detemir (Levemir ) 30

6 Type Onset Peak Insulin NPH/Insulin Regular - Humulin 70/30 - Novolin 70/30 - ReliOn 70/30 Effective Duration 30 min 2 5 hrs hrs Insulin lispro protamine/insulin lispro - Humalog 75/25 Mix - Humalog 50/50 Mix 15 min hours hours Insulin aspart protamine/insulin aspart - Novolog 70/30 Mix min 1 4 hours Up to 24 hours

18 24 hrs Insulin lispro protamine/insulin lispro - Humalog 75/25 Mix - Humalog 50/50

7 Adapted from Hirsch IB. Insulin analogues. N Engl J Med. 2005;352(2):177.

8 WHAT IS THE GOAL?

9 GLYCEMIC GOALS Two ways to assess effectiveness and need for regimen change Self monitoring of blood glucose (SMBG) A1c A1c < 7% Preprandial mg/dL Postprandial < 180mg/dL 1 2 hours after the beginning of the meal Individual patient considerations

< 7% Preprandial 70 130mg/dL Postprandial < 180mg/dL 1 2 hours

11 WHEN TO START INSULIN?

16 HOW DO WE DO IT?

17 Starting Insulin Add long-acting (basal) insulin first NPH, insulin glargine, insulin detemir Approach # units/kg Example: 81kg patient x 0.2 units/kg = 16.2 units 15 units basal insulin at bedtime or before breakfast Approach # 2 Start a fixed bedtime or morning dose of 10 units Example: 10 units basal insulin at bedtime or before breakfast Treat To Target Study

2 units 15 units basal insulin at bedtime or before breakfast Approach # 2 Start a fixed

18 What to do with the oral medications? Metformin KEEP (low risk of hypoglycemia) SFU/Meglitinides consider d/c (risk of hypoglycemia) Thiazolidinediones consider d/c (risk of hypoglycemia/hf) DPP-4 Inhibitors consider continuation Alpha glucosidase inhibitors consider d/c (no added benefit) SGLT 2 consider continuation

of hypoglycemia) Thiazolidinediones consider d/c (risk of hypoglycemia/hf)

19 Which insulin should I start with? Long acting (Basal) NPH, insulin glargine, insulin detemir Considerations Number of injections Timing of injections Duration of action Cost Mealtime (Bolus) Regular insulin, insulin aspart, lispro or glulisine Add to regimen as needed to reach postprandial goals

Number of injections Timing of injections Duration of action Cost Mealtime

20 PATIENT CASES

21 Patient Case MW MW is 54 year old AA male diagnosed with diabetes over a year ago, but only now after a random reading exceeds 300 mg/dl at your office visit is he willing to admit that he has uncontrolled diabetes. He has had a previous heart attack and is taking several cardiovascular and hypertensive medications. His physical exam today is normal. He admits to feeling a little tired, recently, and has been getting up at night to urinate at least two to three times per week.

22 Patient Case MW Last A1c: 10.2% Height: 6 1 Random glucose in office: 358mg/dL SCr: 0.8 mg/dl BP: 128/88 mmhg Weight: 212 lbs (96 kg) BMI: 28 Metformin 1000mg twice daily Foot Exam: normal pulses and sensation Glipizide 10mg twice daily What do we do?

23 WHAT ARE THE NEXT STEPS FOR MW?

24 What are the next steps for MW? Review/Set a goal. Discuss insulin initiation. Start long acting insulin. Approach 2: 10 units at bedtime Discontinue glipizide. Continue metformin. Request fasting SMBG daily and records sent to office. Return to clinic in 3 months.

25 Patient Case MW Date Time Blood Sugar Notes 3/12 7:00 am 346 mg/dl Started insulin 3/13 7:10 am 333 mg/dl 3/14 7:10 am 332mg/dL 3/16 7:06 am 277 mg/dl 3/17 7:49 am 287 mg/dl 3/18 4:15 pm 301 mg/dl Ate out 3/19 8:01 am 266 mg/dl 3/24 8:00 am 278 mg/dl 3/25 7:14 am 280 mg/dl

26 Dose Titration for Insulin If average fasting glucose for 7 days is: > 180mg/dL increase by 6 units or 20% (whichever is greater) mg/dl increase by 4 units or 10% mg/dl increase by 2 units or 10 % mg/dl No change in dose < 90 mg/dl decrease dose by 4 units or 10% If any hypoglycemia OR average fasting glucose is: mg/dl reduce dose by 10% < 60mg/dL reduce dose by 20%

27 Patient Case MW Date Time Blood Sugar Notes 3/12 7:00 am 346 mg/dl Started insulin 3/13 7:10 am 333 mg/dl 3/14 7:10 am 332mg/dL 3/16 7:06 am 277 mg/dl 3/17 7:49 am 287 mg/dl 3/18 4:15 pm 301 mg/dl Ate out 3/19 8:01 am 266 mg/dl 3/24 8:00 am 278 mg/dl 3/25 7:14 am 280 mg/dl

28 What are the next steps for MW? Average blood glucose = 277 mg/dl Increase long acting insulin by 6 units or by 20% Increase from 10 units to 16 units at bedtime Continue fasting SMBG daily and return blood sugars to clinic Return to clinic in 5 weeks

29 Patient Case MW MW returns to clinic. His A1c has fallen to 9.5% with no reports of hypoglycemia. His weight increased by 2.5 lbs and he is currently taking 16 units of basal insulin. On inspection of blood sugar logs, MW has an average fasting blood glucose of 184mg/dL. What are the next steps for MW?

30 What are the next steps for MW? Average blood glucose = 184 mg/dl Increase long acting insulin by 6 units or by 20% Increase from 16 units to 22 units at bedtime Continue fasting SMBG daily and return blood sugars to clinic May also consider self titration in appropriate patients: Check fasting blood glucose daily Increase long acting insulin dose by 2 units every 3 days until fasting blood sugars are consistently in the target range

31 A kink in the plan?? Date Time Blood Sugar Notes 6/17 7:00 am 198 mg/dl 6/18 7:10 am 151 mg/dl 6/19 7:10 am 176 mg/dl 6/20 7:06 am 145 mg/dl Lowest blood sugar 6/24 7:49 am 180 mg/dl Faxed blood sugars 6/25 4:15 pm 234 mg/dl Ate out 6/27 8:01 am 179 mg/dl 6/29 8:00 am 205 mg/dl 6/30 7:14 am 156 mg/dl

32 What are the next steps for MW? Average blood glucose = 180 mg/dl Often blood sugars have no discernable pattern Use of averages helps to determine level of titration Increase long acting insulin by 6 units or by 20% Increase from 16 units to 22 units at bedtime Same plan Continue fasting SMBG daily and return blood sugars to clinic

33 Patient Case ES ES is 60 year old Caucasian female diagnosed with diabetes over 5 years ago, she has been on metformin and long acting insulin at bedtime for 3 years. Her fasting blood sugars are consistently within the desired ranges. Her blood pressure and cholesterol are well controlled on medication therapy and her physical exam is normal. She is compliant with her medications and expresses excitement at the birth of her first grandson.

34 Patient Case ES Last A1c: 8.4% Height: 5 5 Random glucose in office: 201 mg/dl SCr: 1.3 mg/dl BP: 118/90 mmhg Weight: 185 lbs (84kg) BMI: 30.8 Metformin 1000mg twice daily Foot Exam: normal pulses and sensation Insulin glargine 40 units at bedtime What do we do?

35 WHAT ARE THE NEXT STEPS FOR ES?

36 What are the next steps for ES? Review the goal. Consider adding mealtime insulin. Approach # 1: Add to largest meal of the day Approach # 2: Add to meal based on preprandial and bedtime readings Continue long acting insulin at current dose. Assess metformin continuation. Request changes in SMBG: fasting, pre prandial and bedtime and blood sugar logs sent in to office.

38 Patient Case ES ES returns to clinic and is currently taking: insulin glargine 40 units at bedtime Insulin aspart 10 units before dinner Metformin 1000mg twice daily Continue to monitor A1c If A1c still not at goal Adjust mealtime insulin until preprandial/bedtime goals reached Add mealtime insulin to another meal if needed

39 ON THE HORIZON

40 Inhaled Insulin - Afrezza Dry-powder recombinant human regular insulin Administered via Afrezza inhaler; can be used for 15 days Insulin particles reach the lung and dissolve on contact with rapid absorption into systemic circulation Approved for adults > 18 years old with T1DM or T2DM In T1MD, must be used with long acting insulin Not for use in children, pregnancy, breastfeeding or DKA

41 Inhaled Insulin - Afrezza Onset: minutes Peak: 60 minutes Duration of action: hours Unopened packs must be refrigerated Once opened, cartridge must be at room temperature for 10 minutes before use

45 QUESTIONS?

Insulin Initiation and Intensification

Insulin Initiation and Intensification ANDREW S. RHINEHART, MD, FACP, CDE MEDICAL DIRECTOR AND DIABETOLOGIST JOHNSTON MEMORIAL DIABETES CARE CENTER Objectives Understand the pharmacodynamics and pharmacokinetics