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Management of Type 2 Diabetes Mellitus: Initiating Insulin Therapy

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Med-Peds Continuity Clinic Baylor College of Medicine Anoop Agrawal, M.D. Other goals for insulin therapy Patients who no longer have -cell function require a Basal ... – PowerPoint PPT presentation

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Title: Management of Type 2 Diabetes Mellitus: Initiating Insulin Therapy


1
Management of Type 2 Diabetes Mellitus
Initiating Insulin Therapy
  • Med-Peds Continuity Clinic
  • Baylor College of Medicine
  • Anoop Agrawal, M.D.

2
Case One
  • 50 yo male with diagnosed with Type 2 diabetes
    three months ago. He has been on Metformin
    1000mg bid since diagnosis. A1C was 8.7 at time
    of diagnosis.
  • Today Hgb A1c is 7.3 with a FBS of 165 mg/dl
  • You are confident he has been compliant with his
    therapy. What is your next step?

3
Case One
  • A. No change in therapy, recheck A1c in 3 months
  • B. Start Glyburide 5mg bid
  • C. Start Actos 30mg daily
  • D. Start NPH 10 units qhs

4
Case One
  • A. No change in therapy, recheck A1c in 3 months
  • B. Start Glyburide 5mg bid
  • C. Start Actos 30mg daily
  • D. Start NPH 10 units qhs

B, C or D - all acceptable choices
5
ADA Diabetes Algorithm
Diabetes Care, Vol 6, Number 8, August 2006
6
Case One - Clinician Inertia
  • Initiate therapy with metformin and reevaluate
    A1c after 3 months. If goal of 7 not met, then
    advance therapy.
  • It is not necessary to titrate a medication to
    maximal dosage before adding another agent.
  • Going above half the max recommended dosage of a
    sulfonylurea provides little additional benefit.
    (i.e. glyburide 5mg bid is sufficient)
  • Similarly, increasing metformin from 2000mg to
    max of 2550 does little to benefit.

7
Case One - Clinical Inertia
  • A study out of Kaiser Permanente in California
    looked at how many patients moved to next level
    of treatment when A1C was over 8
  • On sulfonlyurea - 35
  • On metformin - 44
  • On two oral agents - 18
  • In general, patients spent 5 years with A1C over
    8 before decision was made to add insulin!

8
Barriers to Starting Insulin Patient Driven
  • Fear of needles/injections and pain
  • Fear of hypoglycemia
  • Belief that once one starts insulin, they will
    soon die
  • Belief that starting insulin means the disease
    has won
  • Fear of insulin induced by the provider
  • if you dont start doing X, Im going to have to
    put you on insulin

9
Barriers to Starting Insulin Provider Driven
  • Unsure how to start and how to adjust
  • Fear of promoting vascular complications
  • Belief that patient compliance will be adversely
    affected
  • Fear of patient rejection
  • Concern for inducing side effects (hypoglycemia,
    weight gain)

10
Decline in ß-cell function UKPDS
25-30 initial non-responders to OHA 5-20 fail
each year by 10-15 yrs, 100 OHA failure
11
Oral Hypoglycemic Agents MOA and Efficacy
Agent MOA ? A1c
Sulfonylureas increase insulin production from ß cells 1 to 2
Biguanides inhibits hepatic glucose production increases insulin sensitivity up to 2
Thiazolidinediones increase insulin sensitivity 0.8 to 1
Alpha-glucosidase inhibitors inhibit glucose absorption 0.5 to 1
12
Oral Agents
  • Sulfonylurea efficacy declines with the
    progressive diminishing ß-cell function.
  • Metformin and Glitazones continue to provide some
    benefit throughout the course of the disease
    especially those with insulin resistance.
  • In order to adhere to ADA and ACE treatment
    goals, physicians should consider initiating
    insulin therapy at the first sign of poor
    response to oral agents.
  • In general, patients with A1c gt10 need to be on
    insulin.

13
Insulins and Duration of Action
14
Patient is on glucovance 2.5/500 2 tabs po bid.
He has had DM II for 5 years. What is your next
course of action?
Initiate insulin therapy with BIDS therapy -
daytime sulfonylurea and nighttime NPH insulin
15
Case Two
  • 45 yo female with Type 2 diabetes for the past 5
    years.
  • Current medications Glipizide 10mg daily and
    Metformin 1000mg bid
  • Today Hgb A1c is 8.5 with a FBS of 150-220 mg/dl
    over past 2 months in her log book.
  • What is your next step?

16
Case Two
  • A. Add on a TZD agent (i.e. Actos)
  • B. Add on a DPP IV agent (i.e. Januvia)
  • C. Add on a long acting insulin at bedtime
  • D. Stop oral drugs and start insulin basal-bolus
    therapy

17
Case Two
  • A. Add on a TZD agent (i.e. Actos)
  • B. Add on a DPP IV agent (i.e. Januvia)
  • C. Add on a long acting insulin at bedtime
  • D. Stop oral drugs and start insulin basal-bolus
    therapy

18
Case Two
  • Add basal insulin!! Do not add a third oral
    antidiabetic agent!
  • Why?
  • Understand the natural course of diabetes, i.e.
    the progressive decline of insulin production
    with time (beta-cell loss)
  • Understand the relationship between insulin and
    hepatic glucose production, and its effect on
    fasting glucose.

19
Bedtime insulin/Daytime Sulfonylurea (BIDS)
General rules of thumb Start with 10 units NPH
qhs Administration is usually between 10 pm and
midnight.
20
Case Two
  • First, focus on getting fasting plasma glucose to
    70-130 mg/dl.
  • QHS insulin will suppress hepatic glucose
    production at overnight, reducing FPG.
  • In the Treat-to-Target Trial, the addition of
    nighttime basal insulin to oral agents lowered
    A1C from 8.6 to 7 in 10 weeks.
  • The study also compared NPH vs. glargine and
    found no difference between NPH and glargine in
    achieving A1C reduction.

21
Case Two - QHS insulin
  • In general, the starting dose at bedtime is less
    important than having a titration algorithm.
  • Typically, start at 10 units qhs or 0.1 to 0.2
    units per kg.
  • Most patients will end up needing 0.5 to 1.0
    units per kg.
  • Titration can be done every 2-3 days by the
    patient until FPG reaches near 100-120 mg/dl.

22
Titration of bedtime insulin
FPG values in preceding 2 days increase in insulin dosage (U/day)
180 mg/dl 6
140-180 mg/dl 4
120-140 mg/dl 2
100-120 mg/dl 0
23
Initiating Basal Insulin Algorithm
  • Once FPG at 70-130 mg/dl and A1c still gt7 then
    start assessing pre-meal sugars.
  • Pre-lunch high add Reg at breakfast
  • Pre-dinner high add NPH at breakfast
  • Pre-bed high add Reg at dinner

Text
Diabetes Care, Vol 6, Number 8, August 2006
24
Insulin Oral Agents
  • Pros
  • Decreased insulin dose
  • Potential for less hypoglycemia
  • Less intensive insulin regimens
  • Cons
  • Increased number of meds decreased compliance
  • Potential for drug interactions
  • Potentially more costly

25
Case Three A 56 yo male with glyburide 5mg
daily, metformin 1gm bid and NPH insulin 35 units
qHS. His A1C is 8. Below is his blood sugar
log.
What is your next course of action?
26
Case Three
  • A. Add Actos 45mg daily
  • B. Add NPH in the AM and continue qHS
  • C. Start regular insulin qam and qpm, along with
    NPH qam and qpm stop glyburide
  • D. Start Lantus once daily, stop NPH continue
    oral medications.

27
Case Three
  • A. Add Actos 45mg daily
  • B. Add NPH in the AM and continue qHS
  • C. Start regular insulin qam and qpm, along with
    NPH qam and qpm stop glyburide
  • D. Start Lantus once daily, stop NPH continue
    oral medications.

28
Case Three
  • As A1c approaches target levels (lt8-8.5),
    postprandial glucose contributes more than 50 to
    value of the A1c.
  • Use basal insulin to achieve rapid reduction in
    A1cs greater than 8.5
  • However, to achieve goal of 6.5-7 may require
    the addition of prandial insulin.

29
ADA Diabetes Algorithm
Diabetes Care, Vol 6, Number 8, August 2006
30
Options in basal insulin
  • Insulin Glargine in place of NPH
  • Pros
  • ease of use (once daily)
  • 35 lower incidence of hypoglycemia
  • Cons
  • formulary restrictions/cost
  • NPH equally effective in compliant patients

31
Starting Insulin Only
  • Normal daily insulin secretion is 0.5 to 0.7
    u/kg/day
  • Hence, starting insulin doses range from 0.3 to
    1.0 u/kg/day, with the average being 0.5 to 0.8
    u/kg/day.
  • Factors in choosing 24 hour insulin needs
    physical activity level, weight, renal failure,
    coexisting illness, eating habits

32
Calculating 24-hour insulin needs
Physical Activity Level Normal Weight Obese
High 0.3 U/kg 0.5 U/kg
Moderate 0.4 U/kg 0.6 U/kg
Low 0.5 U/kg 0.8 U/kg
Coexisting Illness (CKD) Subtract 0.2 U/kg Subtract 0.2 U/kg
Big eater eating habits Add 0.1 U/kg Add 0.1 U/kg
33
Insulin Adjustments
  • Ms. Smith is on NPH 40u/Reg 14u qam, Reg 10u
    before dinner and NPH 30u qhs. She has reported
    multiple daytime and nighttime episodes of
    hypoglycemia. You decide to change NPH to
    glargine. How do you convert NPH to glargine?
  • 80 of NPH dose initial glargine dose

34
Other goals for insulin therapy
  • Patients who no longer have ß-cell function
    require a Basal-Bolus Insulin Regimen, i.e. NPH
    bid/glargine qd combined with short acting
    insulin premeals.
  • Premix insulins (70/30, 75/25) are more difficult
    to adjust and hence less popular. Serves as a
    good option for patients resistant to more than
    two injections of insulin a day.

35
Common Questions
  • How often should blood sugar be checked?
  • At least as often as an injection of insulin is
    given
  • Can insulins be mixed (in same syringe)?
  • NOT with Glargine
  • Always draw up Short Acting Insulin before
    intermediate acting
  • Remember First draw up clear, then cloudy -
    short acting insulins are clear, long acting are
    cloudy (except glargine - is clear)

36
Common Questions
  • What to do with insulin dose when NPO?
  • Continue glargine at same dose
  • Skip Short Acting Insulin
  • FBG level should not vary if the glargine dose
    is correct.
  • If using NPH pt should take 50 of dose
  • Skip SAI

37
New Insulin Therapies
  • Exubera - inhaled insulin
  • no advantage over injectable insulin
  • will require monitoring with PFTs
  • Now off the market due to lack of use
  • New fast acting agents glulisine (Apidra)
  • New intermediate to long acting (basal) insulin
    detemir (Levemir)

38
Summary
  • Oral agents have limited efficacy which will wane
    over a period of time.
  • Insulin initiation should be considered in any
    patient on two oral agents at maximum doses and
    A1C over 7.
  • Combination therapy of an oral agent with insulin
    is safe and effective.
  • Choosing and dosing an insulin formulation should
    take into account the patients profile and
    lifestyle.

39
References
  • Nathan, DM. et al. Management of Hyperglycemia
    in Type 2 Diabetes A Consensus Algorithm for the
    Initiation and Adjustment of Therapy. Diabetes
    Care Aug 2006291963-1972.
  • Nelson SE, Palumbo PJ. Addition of Insulin to
    Oral Therapy in Patients with Type 2 Diabetes.
    The American Journal of Medical Sciences May
    2006331257-63.
  • McMahon G, Dluhy RG. Intention to Treat -
    Initiating Insulin and the 4-T Study. New
    England Journal of Medicine Oct 073571759-1761.
  • Hirsch IB. Insulin Analogues. New England
    Journal of Medicine Jan 05352174-83.
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