Intended as informational for health care professionals only

1
Intended as informational for health care
professionals only Not intended as consumer
information to diagnose or treat any condition
2
Injectable Type 2 Diabetes Medications

• Eric Lind Johnson, M.D.
• Assistant Professor
• Department of Family and Community Medicine
• University of North Dakota School of Medicine
• And Health Sciences
• Assistant Medical Director
• Altru Diabetes Center
• Grand Forks, ND

3
Objectives

• Understand betacell decline and its relevance in
  management of type 2 diabetes
• Understand role of non-insulin injectable
  medications in management of type 2 diabetes
• Understand role of insulin in the management of
  type 2 diabetes

4
Goals of Glucose Management

• Targets for glycemic (blood sugar) control

lt6 for certain individuals

• American Diabetes Association. Diabetes Care.
  200932(suppl 1)
• Implementation Conference for ACE Outpatient
  Diabetes Mellitus Consensus Conference
  Recommendations Position Statement at
  http//www.aace.com/pub/pdf/guidelines/OutpatientI
  mplementationPositionStatement.pdf. Accessed
  January 6, 2006.
• AACE Diabetes Guidelines 2002 Update. Endocr
  Pract. 20028(suppl 1)40-82.

5
Non-Insulin Injectable Type 2 Medications
6
Glucagon-like Peptide-1 (GLP-1)

• Gut hormone
• Stimulates pancreas to secret insulin
• Suppresses glucagon action
• Many target organs
• Weight regulation
• Caution in renal or hepatic impairment

7
GLP-1

• Exenatide (Byetta) GLP-1 mimetic
• Liraglutide (Victoza) GLP-1 analog
• Both available in pen injectors (easy)
• Modest weight loss
• Combined with other agents except DPP-IV
  inhibitors or insulin (exenatide has basal
  insulin data)

8
GLP-1 Caveats

• Nausea, vomiting
• Pancreatitis
• Medullary thyroid carcinoma in rodents
  (liraglutide)
• Hypoglycemia combined with sulfonyurea

9
Pramlintide-Synthetic Amylin(Symlin)

• Amylin secreted by normal pancreas along with
  insulin to regulate blood glucose
• Enhances Postprandial control. Used in Type 1 and
  Type 2 patients
• Used as adjunct to insulin
• Available in pen injector
• Possible significant hypoglycemia

10
Combination Drug Therapy

• Consider early if failing monotherapy
• Generally additive or synergistic effects
• Triple or quadruple non-insulin drug therapy
• -limited benefit in many
• -safe for many
• Insulin is often a better,more potent choice

11
Case Study
12
Insulin TherapyType 2 Diabetes

• Most type 2 diabetes patients will require
  insulin due to beta cell decline
• Modern insulins are more predictable, reliable,
  and easy to use
• This isnt your fathers/mothers diabetes
• Nearly all insulins come in easy to use
  comfortable pen devices accepted by patients

13
Case 1

• 52 y/o white female
• Diagnosed Type 2 DM in 1998
• PMH HTN, Dyslipidemia,
  post-menopausal
• FH Positive for MI in father and uncle
• Non-smoker, 1-2 alcohol drinks per week
• Walks a lot at work

14
Case 1

• Medications
• Metformin 1000 mg BID
• Glyburide 10 mg BID
• Pioglitazone 45 mg daily
• Simvistatin 40 mg daily
• ASA 81 mg
• Lisinopril 10 mg daily

15
Case 1

• Physical Exam
• Height 52
• Weight 210 lbs
• BMI 38.4
• Otherwise normal except trace ankle edema

BMI calculator http//www.nhlbisupport.com/bmi/
16
Case 1

• A1C 8.6
• Fasting glucose 205
• Blood Glucose at home about 150 checked
  regularly
• What should be next for this patient?

17
Beta-cell function declines as diabetes
progresses
Beta-cell function decline over time
100
Diagnosis
Beta-cell decline exceeds 50 by time of diagnosis
75
IGT
Beta-cell function ()
Insulininitiation
50
PostprandialHyperglycemia
25
Type 2 Diabetes
0
4
4
12
8
0
8
12
Years from diagnosis
Lebovitz H. Diabetes Rev 19997139-153.
18
ADA Medication Algorithm

• Metformin at diagnosis for most patients
• Insulin may be considered
  as second line therapy

Nathan et al Diabetes Care 2009
19
AACE Medication Algorithm

• Metfomin (possibly others) are first line therapy
  in type 2 diabetes
• Insulin may be a first line therapy if A1C
  gt9

www.aace.com/pub
20

• Insulin Therapies

21
Insulin Therapy

• All Type 1 patients at diagnosis
• All type 2 patients will require insulin if they
  live long enough
• -7 to 10 years post diagnosis
• -A1C gt9
• -Function of many non-insulin meds based on
  presence of native insulin

22
Insulin Therapy

• Modern insulins safer and
  more predictable
• Most insulin types come in pen injectors
• Pen injectors easy to use, to teach, less
  cumbersome than vials/syringes

23
Rapid Acting Insulin

• Aspart (Novolog)
• Lispro (Humalog)
• Glulisine (Apidra)
• (Human Regular)
• Taken with meals and snacks
• Bolus insulin

24
Long-Acting Insulin

• Detemir (Levemir)
• Glargine (Lantus)
• Human NPH (N)
• Taken 1 or 2 times daily
• Basal insulin

25
Basal Insulin in Type 2 Diabetes

• Glargine (Lantus), Detemir (Levemir)
• Good, potent add-on for improved A1C
• Second line agent for many patients
• A1C gt9, diabetes longer than 5 to 7 years
• AACE ? Weight benefit with Detemir
• Pen injectors easy

26
Basal Insulin in Type 2 Diabetes

• Some oral meds may be continued
• -metformin, maybe TZD, maybe SU, maybe
  gliptin (sitagliptin)
• Glargine (Lantus) or Detemir (Levemir) started at
  10 units at HS
• Increase 3 units every 3 to 5 days until fasting
  blood sugars lt110 (or lt140)
• Most type 2 on 50-80 units/day

27
Case 1

• Was started on basal (Lantus or Levemir)
• 10 units at hs, increase 3 units every 5 days
  until FBS lt110 consistently without signficant
  hypoglcymia
• Reached goal with 55 units basal insulin
  daily

28
Premix Insulins

• 70/30, 75/25, 50/50
• Combine R or rapid acting with NPH or an
  NPH-like component
• Certain applications may be appropriate
• Limitation change 2 insulins at once

29
Intensifying Insulin Therapy
30
Recall.Case 1

• Glargine or Detemir now at 55 units q hs
• A1C is now 7.6
• SMBG consistently fasting lt140
• 2 hour post-prandial 190s-220s
• Now what?

31
Case 1

• Next step would be to add rapid acting insulin
  bolus to largest meal daily (usually evening
  meal) to address post-prandial glucose
• 90/10 rule Decrease basal by 10, give that 10
  as rapid acting insulin (bolus)

32
Relative Contributions of Fasting and
Postprandial Plasma Glucose to Total Glycemic
Excursions as a Function of A1C
Monnier L et al. Diabetes Care. 200326881-885.
33
Case 1

• Metformin was continued
• Glargine or detemir(recall already using)
• decreased 10 to 50 units q hs
• Add Rapid acting
  (Aspart, glulisine,or lispro)
• 5 units with largest meal
• (10of daily total)

34
Case 1

• So, this patient is using 90/10 rule for
  advancement from once daily basal insulin to a 2
  injection daily program
• 50 units glargine or detemir 90 of daily total
• 5 units rapid acting 10 of daily total

35
90/10 Rule

• As type 2 patients take larger doses of basal
  insulin, temptation is to split basal dose and
  give BID
• If going to 2 injection program, better to keep
  basal once daily and add a rapid acting insulin
  injection with largest meal (90/10 rule)

36
Advanced Basal/Bolus Insulin Therapy

• Mulitple Daily Injections (MDI)

37
Basal/Bolus Insulin Multiple Daily Injections
(MDI)

• Simple 2 injections, once daily basal (long
  acting) insulin, once daily bolus (rapid acting)
  insulin with largest meal (90/10 rule)
• Advanced 4 injections, once daily basal (long
  acting) insulin, bolus insulin (rapid acting)
  with each meal (MDI)

38
Basal/Bolus Insulin Multiple Daily Injections
(MDI)

• Many patients will accept a 2 injections program
  as first step in advancing to MDI (90/10 rule)
• Many patients will resist going from a
• 1 injection daily regimen to a
  
• 4 injections daily regimen (Basal
  mealtime insulin)
• Eventually work toward 4 injections daily

39
Basal/Bolus Insulin Multiple Daily Injections
(MDI)

• Basal insulin daily bolus insulin
  with each meal
• 2 strategies
• 1)Bergenstal formula
• (if not carb counting)
• 2)Insulin/carb ratio (if carb counting)

Diabetes Care July 2008 311305-1310
40
MDI Non-Carb CountingBergenstal Formula
41
Basal/Bolus Insulin Multiple Daily Injections
(MDI)

• Bergenstal formula (if not carb counting)
• Of total daily dose, 50 basal insulin
• 50 bolus insulin
• First, reduce basal (glargine or detemir) by
  50 at initiation of bolus insulin

42
Basal/Bolus Insulin Multiple Daily Injections
(MDI)

• Bergenstal formula (contd)
• Then, add mealtime
• rapid acting insulin (bolus)(aspart)
• 50 of total daily dose
• Split total rapid acting(aspart,lispro,glulisine)
  as
• 50 with largest meal
• 33 with next largest meal
• 17 with smallest meal

43
Basal/Bolus Insulin Multiple Daily Injections
(MDI)

• Bergenstal formula for MDI
• Example
• Patient currently on 50 units of glargine or
  detemir once daily
• -cut glargine by 50 (25 units daily)
• (this will now be 50 of total daily insulin)

44
Basal/Bolus Insulin Multiple Daily Injections
(MDI)

• Bergenstal formula (contd)
• Add mealtime rapid acting insulin (bolus)
• -25 total units daily
  (this will be 50
  of total daily insulin dose)
• Given as
• 50 of this with largest meal 13 units
• 33 of this with next largest meal 8 units
• 17 of this with smallest meal 4 units

45
Basal/Bolus Insulin Multiple Daily Injections
(MDI)

• So, our patient finishes this consult with
• Basal
• (50 of daily total) 25 units once daily
• Rapid acting 13 units largest meal
• (50 of daily total) 8 units next largest
• 4 units
  smallest meal
• Doses are titrated per SBGM

46
Modified Bergenstal Formula

• 50 basal long acting
• in this case 25 units of Lantus or Levemir
• 50 bolus rapid acting
• 25 total units aspart/lispro/glulisine
• split 3 ways
• 8 units with each meal

47
MDI Carb Counting
48
Basal/Bolus Insulin Multiple Daily Injections
(MDI)

• In carb counting MDI, reduce basal 30-40
  when starting bolus (mealtime) insulin in type 2
  diabetes
• Bolus (mealtime insulin) 2u/15 gram carb
• Correction (sensitivity factor)
• 1 u to drop blood sugar 30 points
• Need to know pre-meal blood sugar

49
Calculating Bolus with Carb Counting and
Correction

• Example
• Blood sugar pre-meal was 200, target 110
• 60gram carb meal 2u/15gram 8 units
• Correction insulin 1u/30pts3 units (90pts)
• Meal (carb) 8 units correction 3 units 11
  units for this meal
• Target 2 hour post meal to lt160-180

50
Summary

• Most patients with type 2 diabetes will
  eventually require insulin
• Basal insulin once daily is an easy and effective
  therapy for most patients with type 2 diabetes

51
Contact Info/Slide Decks/Media

• e-mail
• eric.l.johnson_at_med.und.edu
• ejohnson_at_altru.org
• Facebook
• Search North Dakota Diabetes on Facebook
• Slide Decks (Diabetes, Tobacco,
  other)http//www.med.und.edu/familymedicine/slide
  decks.html
• iTunes Podcasts (Diabetes) (Free
  downloads)http//www.med.und.edu/podcasts/ or
  iTunesgtgt search UND Medcast (updated
  soon)
• WebMD Page (under construction)http//www.webmd.
  com/eric-l-johnson
• Diabetes e-columns (archived) http//www.ndhealth
  .gov/diabetescoalition/DrJohnson/DrJohnson.htm

52
Acknowledgements

• William Zaks, M.D., Ph.D.,
• Assistant Medical Director
• Altru Diabetes Center
• Grand Forks, ND
• Slide and Content Review