Intended as informational for health care professionals only
Not intended as consumer information to diagnose or treat any condition
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
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
Goals of Glucose Management
Targets for glycemic (blood sugar) control
A1C (%)
Fasting (preprandial) plasma
glucose
Postprandial (after meal)
plasma glucose
ADA
AACE
<7*
≤6.5
70-130 mg/dL <110 mg/dL
<180 mg/dL
<140 mg/dL
*<6 for certain individuals
• American Diabetes Association. Diabetes Care. 2009;32(suppl 1)
• Implementation Conference for ACE Outpatient Diabetes Mellitus Consensus Conference Recommendations: Position Statement
at http://www.aace.com/pub/pdf/guidelines/OutpatientImplementationPositionStatement.pdf. Accessed January 6, 2006.
• AACE Diabetes Guidelines – 2002 Update. Endocr Pract. 2002;8(suppl 1):40-82.
Non-Insulin Injectable Type 2
Medications
Glucagon-like Peptide-1
(GLP-1)
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Gut hormone
Stimulates pancreas to secret insulin
Suppresses glucagon action
Many target organs
Weight regulation
Caution in renal or hepatic impairment
GLP-1
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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)
GLP-1 Caveats
• Nausea, vomiting
• Pancreatitis
• Medullary thyroid carcinoma in rodents
(liraglutide)
• Hypoglycemia combined with sulfonyurea
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
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
Case Study
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 isn’t your fathers/mothers diabetes”
• Nearly all insulins come in easy to use
comfortable pen devices accepted by patients
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”
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
Case #1
• Physical Exam:
Height: 5’2”
Weight: 210 lbs
BMI: 38.4
Otherwise normal except trace ankle
edema
BMI calculator: http://www.nhlbisupport.com/bmi/
Case #1
• A1C 8.6
• Fasting glucose 205
• Blood Glucose at home “about 150”
checked “regularly”
• What should be next for this patient?
Beta-cell function declines as
diabetes progresses
Beta-cell function decline over time
100
Diagnosis
75
Beta-cell
function (%)
50
Beta-cell decline exceeds 50%
by time of diagnosis
IGT
Insulin
initiation
Postprandial
25
Type 2 Diabetes
Hyperglycemia
0
12
8
Lebovitz H. Diabetes Rev 1999;7:139-153.
4
0
Years from diagnosis
4
8
12
ADA Medication Algorithm
• Metformin at diagnosis for most patients
• Insulin may be considered
as second line therapy
Nathan et al Diabetes Care 2009
AACE Medication Algorithm
• Metfomin (possibly others) are first line
therapy in type 2 diabetes
• Insulin may be a first line therapy if
A1C >9
www.aace.com/pub
Insulin Therapies
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 >9%
-Function of many non-insulin meds
based on presence of native insulin
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
Rapid Acting Insulin
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•
•
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Aspart (Novolog)
Lispro (Humalog)
Glulisine (Apidra)
(Human Regular)
• Taken with meals and snacks
• “Bolus” insulin
Long-Acting Insulin
• Detemir (Levemir)
• Glargine (Lantus)
• Human NPH (N)
• Taken 1 or 2 times daily
• “Basal” insulin
Basal Insulin in Type 2 Diabetes
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Glargine (Lantus), Detemir (Levemir)
Good, potent add-on for improved A1C
Second line agent for many patients
A1C >9, diabetes longer than 5 to 7 years
AACE: ? Weight benefit with Detemir
Pen injectors easy
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 <110 (or <140)
• Most type 2 on 50-80+ units/day
Case #1
• Was started on basal (Lantus or Levemir)
• 10 units at hs, increase 3 units every 5
days until FBS <110 consistently without
signficant hypoglcymia
• Reached goal with
55 units basal insulin daily
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
Intensifying Insulin Therapy
Recall….Case #1
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•
•
Glargine or Detemir now at 55 units q hs
A1C is now 7.6
SMBG consistently fasting <140
2 hour post-prandial 190’s-220’s
• Now what?
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)
Relative Contributions of Fasting and Postprandial Plasma
Glucose to Total Glycemic Excursions as a Function of
A1C
80
Postprandial hyperglycemia
Contribution (%)
Fasting hyperglycemia
60
40
20
0
1
(<7.3)
2
3
4
(7.3–8.4) (8.5–9.2) (9.3–10.2)
Monnier L et al. Diabetes Care. 2003;26:881-885.
A1C (%) Quintiles
5
(>10.2)
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
(10%of daily total)
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
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)
Advanced Basal/Bolus
Insulin Therapy
Mulitple Daily Injections (MDI)
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)
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
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 31:1305-1310
MDI Non-Carb Counting
“Bergenstal” Formula
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
Basal/Bolus Insulin
Multiple Daily Injections (MDI)
• “Bergenstal” formula (cont’d)
• 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
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)
Basal/Bolus Insulin
Multiple Daily Injections (MDI)
• “Bergenstal” formula (cont’d)
• 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
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
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
MDI Carb Counting
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
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/30pts=3 units (90pts)
• Meal (carb) 8 units + correction 3 units=
11 units for this meal
• Target 2 hour post meal to <160-180
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
Contact
Info/Slide
Decks/Media
e-mail
eric.l.johnson@med.und.edu
ejohnson@altru.org
Facebook
Search “North Dakota Diabetes” on Facebook
Slide Decks (Diabetes, Tobacco, other)
http://www.med.und.edu/familymedicine/slidedecks.html
iTunes Podcasts (Diabetes) (Free downloads)
http://www.med.und.edu/podcasts/ or iTunes>> 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
Acknowledgements
• William Zaks, M.D., Ph.D.,
Assistant Medical Director
Altru Diabetes Center
Grand Forks, ND
Slide and Content Review