An update in outpatient type 2 diabetes
This presentation is the property of its rightful owner.
Sponsored Links
1 / 52

An Update in Outpatient Type 2 Diabetes PowerPoint PPT Presentation


  • 90 Views
  • Uploaded on
  • Presentation posted in: General

An Update in Outpatient Type 2 Diabetes. Elizabeth Stephens, MD Endocrinology- PACE Clinic Providence Portland Medical Center January 2009. Many topics to discuss…. What should our goal A1c be in those with type 2 diabetes and cardiovascular disease?

Download Presentation

An Update in Outpatient Type 2 Diabetes

An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -

Presentation Transcript


An update in outpatient type 2 diabetes

An Update in Outpatient Type 2 Diabetes

Elizabeth Stephens, MD

Endocrinology- PACE Clinic Providence Portland Medical Center

January 2009


An update in outpatient type 2 diabetes

Many topics to discuss…

  • What should our goal A1c be in those with type 2 diabetes and cardiovascular disease?

  • Does continuous glucose monitoring help improve control in diabetes?

  • Are there any other new updates?

    • ADA guidelines 2009, monitoring in type 2 dm, aspirin in diabetes

  • A brief review of a case that illustrates treatment options and frequent questions


Can intensive glucose control it reduce the risk of cvd in high risk type 2 dm

Can intensive glucose control (IT) reduce the risk of CVD in high risk type 2 DM?

  • ACCORD (NEJM 2008;358:2545)

    • 2X2 factorial design to also look at lipid and BP

    • Due to increased mortality in IT group, study was halted 18 months early

  • ADVANCE (NEJM 2008;358:2560)

    • IT included gliclazide (long-acting sulfonylurea)

      • Also looked at BP lowering with ACEI + diuretic

    • Study extended at 3 yrs due to low event rates

  • VADT (NEJM 2009;360)

    • Identical treatment of BP, lipids and lifestyle


Comparing studies baseline

Comparing Studies- Baseline

Skyler J et al, Diabetes Care 2009;32:187


Comparing studies intervention it vs ct

Comparing Studies- Intervention(IT vs CT)

Skyler J et al, Diabetes Care 2009;32:187


Study comparisons outcomes it vs ct

Study Comparisons- Outcomes(IT vs CT)

Skyler J et al, Diabetes Care 2009;32:187


An update in outpatient type 2 diabetes

What does it mean?

  • Benefit likely differs with diabetes duration and underlying complications/CVD

  • Treatment strategies probably critical, especially between ACCORD and ADVANCE

  • Hypoglycemia effect important but it’s role in outcomes not clear yet…


Benefits of early intensive glucose control

Benefits of Early Intensive Glucose Control

  • UKPDS Follow-Up (9 yrs after completion), 4209 pts, newly dx type 2 dm at enrollment, managed with IT or CT

    • Between group differences were lost < 1 year

    • Reduction in microvascular risk were maintained and MI/death emerged during post-trial follow-up

  • 382 Chinese with newly dx type 2 dm

    • Randomized to IT with pump, injections or oral agents

    • More achieved glucose control with insulin, and 51% in remission at one year (no meds) after pump therapy

Holman RR et al. NEJM 2008;359:1577; Weng J et al. Lancet 2008;371:1753


Summary of ada glycemic control section 2009

Summary of ADA Glycemic Control Section-2009

  • Lowering A1c < 7% has been shown to reduce microvascular & neuropathic complications in type 1 & 2 DM

  • RCT have not shown significant reduction in CVD with IT in type 1 & 2 DM

    • Long-term f/u of DCCT and UKPDS suggest benefit with A1c at or below 7%

      • This may be a better target for those with shorter duration of DM, longer life expectancy and no significant CVD

    • Less stringent goals may be appropriate for those with a history of severe hypoglycemia, limited life expectancy, extensive complications/comorbidities, and those where the general goal is “difficult to attain”

Diabetes Care 2008;32:S19


What is continuous glucose monitoring

What is continuous glucose monitoring?

  • Measures glucose levels in interstitial fluid (skin)

  • Readings every 1-5 minutes

    • With alarms set by wearer

  • Costs between $800-1400 for device

    • $35-60 per sensor


Continuous glucose monitoring systems

Continuous Glucose Monitoring Systems

Medtronic

DexCom

Abbott Navigator


An update in outpatient type 2 diabetes

  • 322 people with type 1 DM on IT

    • Randomized to sensor or home monitoring

  • Stratified by age and baseline A1c

    • 67-85% were managed with insulin pumps

    • Monitoring on average 5-7 times per day

  • Evaluated change in A1c at 26 weeks

NEJM 2008;359


Results

Results

34% vs 9% got to

A1c 7% (p=.005)

  • Benefit seen in those > 25 yo

    • A1c  .53%

    • Also used more frequently in adults

    • No difference in hypoglycemia

  • Effect likely reflects abilities and understanding of technology

No difference

In control

27% vs 12% reached A1c 7% (p=.01)


Management of hyperglycemia in type 2 diabetes 2009 tier 1 step 1

Management of Hyperglycemia in Type 2 Diabetes 2009: Tier 1- Step 1

Nathan DM et al, Diabetes Care 2009; 32:193-203


Management of hyperglycemia in type 2 dm tier 1 step 2

Management of Hyperglycemia in Type 2 DM: Tier 1- Step 2

**In 2009 guidelines, TZD’s removed as step 2 therapy…

Nathan DM et al, Diabetes Care 2009; 32:193-203


Management of type 2 dm tier 2 less well validated

Management of Type 2 DM: Tier 2 (Less well validated)

Nathan DM et al, Diabetes Care 2009; 32:193-203


Management of hyperglycemia in type 2 dm other therapy

Management of Hyperglycemia in Type 2 DM: Other Therapy

Nathan DM et al, Diabetes Care 2009; 32:193-203


What about monitoring in type 2 diabetes

What about monitoring in type 2 diabetes?

  • 2 recent studies in those on orals:

    • 184 pts with newly diagnosed type 2 dm, randomized to SMBG (8x per week) or none (O’Kane MJ et al, BMJ 2008;336:1174)

      • No difference in A1c, and those monitoring scored worse on the depression subscale

    • 453 pts with non-insulin treated type 2 dm, A1c > 6.2% and not monitoring, randomized to intensive SMBG, SMBG or usual care (Simon J et al, BMJ 2008; 336:1177)

      • At 1 year, costs with SMBG were higher and SMBG groups had lower quality of life compared with usual treatment

  • Monitoring still recommended for those using insulin


Aspirin use in diabetes jpad and popadad

2539 Japanese with type 2 dm

81/100mg aspirin vs non-aspirin group, rx for 4.37 years

No difference in events overall

Hazard Ratio .80 (95% CI 0.58-1.10)

Marginal significant in those > 65 (HR 0.68; 95% CI, 0.46-0.99)

 risk of GI bleed/retinal hemorrhage with ASA

Generalizability of results?

1276 Scottish with type 1 or 2 + ABI < .99

Rx PBO, ASA +/- antioxidant

Median followup 6.7yrs

No benefit with ASA

HR .98 (95% CI, .76 -1.26)

No benefit with anti-oxidant

HR 1.21 (95% CI, .78 -1.89)

Study underpowered and controversial

Aspirin Use in Diabetes- JPAD and POPADAD

Ogawa H et al. JAMA 2008; 300: 2131-2141;Belch J et al. BMJ 2008;337:a1840


Other updates for 2008

Other Updates for 2008

  • Inhaled insulin was taken off the market

    • Six cases of primary lung malignancies in users

  • Exenatide (Byetta) had warning added for pancreatitis

    • Once- weekly formulation likely available in 2010

  • More DPP-IV medications likely to come available

    • Saxagliptin, alogliptin

  • Labeling for metformin changed (CHF now a warning)

  • Average glucose to be reported with A1c results


An update in outpatient type 2 diabetes

New data on Average Mean Blood Glucose

  • Relationship defined between average blood glucose levels and A1c through regression analysis

  • Included data on 507 subjects

    • Obtained 2700 glucose values for each patient

  • Conversion calculator available at www.diabetes.org

  • Likely to be reported with A1c in the future

Nathan DM, Diabetes Care 2008;31:1473


Case for adding a third agent

Case for Adding a Third Agent

  • 58 year-old with history of hypertension, arthritis and type 2 diabetes

  • Now on metformin 1000mg bid, glipizide 10mg bid

  • A1c is 9.5%

  • What would you add?


Options at this point include

Options at this point include:

  • TZD: pioglitazone (Actos) or rosiglitazone (Avandia)

  • Exenatide (Byetta- GLP1 agonist)

  • Sitagliptin (Januvia- DPP4 inhibitor)

  • Insulin


Lots of controversy with tzd s

Lots of controversy with TZD’s…


Considerations with tzds

Considerations with TZDs

  • Both TZD’s are associated with fluid retention

    • Estimated as a 2-fold increase

    • Even greater with insulin use

  • Start with low doses:

    • Can sometimes see some benefit with rosiglitazone 2mg or pioglitazone 15 mg with less risk of side effects

  • Remember there is a slow response

    • Generally can take up to 3 months before maximal effect is seen

  • Contraindicated in those with ALT >2.5 x upperlimit of normal. Use with caution and monitor more often if ALT < 2.5 x upper limit of normal


  • An update in outpatient type 2 diabetes

    GLP-1 Modulates Numerous Functions in Humans

    GLP-1: Secreted upon the ingestion of food

    Promotes satiety and reduces appetite

     cells:

     Postprandialglucagon secretion

    Liver: Glucagon reduces hepatic glucose output

     cells:Enhances glucose-dependent insulin secretion

    Stomach: Helps regulate gastric emptying

    Data from Flint A, et al. J Clin Invest. 1998;101:515-520;Data from Larsson H, et al.Acta Physiol Scand. 1997;160:413-422; Data from Nauck MA, et al. Diabetologia. 1996;39:1546-1553;Data from Drucker DJ. Diabetes. 1998;47:159-169.


    Options in glp 1 medications

    Exenatide (Byetta)

    Exogenous GLP-1

    Injectable

    A1c  ~ 1-2%

    Expensive

    Side-effects include nausea, vomiting which generally improve with use

    Weight loss

    Sitagliptin (Januvia)

    Enzyme inhibitor

    Oral

    A1c  ~ .8-1%

    Expensive

    Fewer side-effects

    Weight neutral

    Options in GLP-1 Medications


    Percentage of participants choosing each treatment option for the management of type 2 diabetes

    Percentage of Participants Choosing Each Treatment Option for the Management of Type 2 Diabetes

    Halperin F et al. N Engl J Med 2008;358:e8


    What would i have done for this patient

    What would I have done for this patient?

    • Talked to him about options

      • Side effects, cost, need for injection

      • Consider exenatide (Byetta)

    • To get him to an A1c goal of < 7% your best bet at this point would be insulin


    An update in outpatient type 2 diabetes

    Psychological Insulin Resistance

    • From the patient

      • Loss of control

      • Poor self-efficacy

      • Personal failure

      • Perceived disease severity

      • Injection-related anxiety

      • Perceived lack of positive gain

    • From the provider

      • Fearful of time needed for education/mgmt

      • Avoiding confrontation

      • Concerns about

        • Hypoglycemia

        • Weight gain

    Polonsky WH et al, Clinical Diabetes 2004;22:147


    An update in outpatient type 2 diabetes

    Insulin Options

    Basal Onset Peak Duration

    Bolus


    Initiation of insulin

    Initiation of Insulin

    Start with bedtime intermediate-acting insulin (NPH or Detemir) or bedtime or morning long-acting insulin (Glargine)

    Initiate with 10 units or .2 units/kg

    Check FBG daily and increase dose by 2 units every 3 days until fasting levels are in the target range (70-130mg/dl)

    Can increase the dose by larger increments (4 units) every 3 days if fastings are > 180 mg/dl

    If hypoglycemia occurs, reduce dose by > 4 units or 10% whichever is greater

    Nathan DM et al, Diabetes Care 2009;32:193


    An update in outpatient type 2 diabetes

    Background

    (Basal) Insulin

    (ie Lantus or NPH)

    + Oral Agent(s)

    Background and

    Mealtime Insulin

    (basal+bolus)

     Sensitizer(s)

    • Premixed Insulin

    • (ie 70/30)

    • Sensitizer(s)

    • Elevated FPG

    • Stable daytime BG

    • Overwhelmed

    • Desire single injection

    • Elevated PPG

    • Increasing daytime BG

    • Regular schedule

    • Desires to minimize

    • number of injections

    • Elevated fasting

    • and/or post-meal

    • Intensive control

    • More flexibility

    • Erratic schedule

    Adjust to Target Basal/Bolus

    Treat to target

    57-70%

    Premixed studies

    42-70%

    73%

    Insulin Initiation Regimens

    Glycemic Factors

    Patient Factors

    Glycemic Control Achieved

    % with A1c < 7% or <7%

    Courtesy of R. Bergestal, IDC, Minnestota


    Other patient issues to consider when starting insulin

    Other patient issues to consider when starting insulin

    Injection frequency and monitoring

    Abilities, comprehension and safety

    Cost

    BG patterns

    Schedule

    Hypoglycemia

    Devices to make it easier


    An update in outpatient type 2 diabetes

    Improvement of Glycemic Control in Subjects With Poorly Controlled Type 2 DiabetesComparison of two treatment algorithms using glargine

    Algorithm 1: physician-managed

    adjustment

    Algorithm 2: Patient self-adjustment

    FBG

    Insulin dose

    Algorithm 1

    (n = 2,315)

    Algorithm 2

    (n = 2,273)

    Algorithm 1

    Algorithm 1

    Algorithm 2

    Algorithm 2

    0

    50

    170

    Pt

    45

    -0.25

    150

    40

    MD

    -0.50

    Insulin dose (IU)

    FBG (mg/dl)

    130

    35

    A1C (%)

    -0.75

    MD

    30

    110

    Pt

    MD

    25

    -1.00

    Pt

    -1.08

    20

    90

    -1.25

    0

    2

    4

    6

    8

    10

    12

    14

    16

    18

    20

    22

    24

    -1.22

    Weeks since randomization

    P < 0.001

    Davies M et al. Diabetes Care 2005;28:1282-1288


    Continuation of oral agents

    Continuation of Oral Agents

    Metformin: Useful to continue to reduce insulin requirements and weight gain

    TZD’s: May help to reduce insulin requirements, but beware of additional weight gain and fluid retention when used in combination with insulin

    Not recommended now with rosiglitazone

    Sulfonylureas: May need adjustment/discontinuation if hypoglycemia exists or if starting prandial insulin


    Follow up

    Follow Up

    • After you start him on insulin (glargine 10 units Qhs) he relocates to California

    • He returns to see you for follow up 3 years later

    • His current regimen is:

      • 56 units of Glargine BID + 30 units Lispro with meals

    • He reports BG “all over the map” ranging from 50-330mg/dl but monitoring only 1-2 times per day

    • A1c 10.9%


    Issues to consider

    Issues to consider

    • NPH vs Glargine in significant insulin resistance

      • My experience has been that NPH, with a peak, tends to control BG better in those with more insulin resistance

    • Consider adding metformin

    • Make sure he is taking injections

      • Does he have the right size syringes?

        • .3cc= 30units, .5cc= 50units, 1cc= 100units

      • Teach him how to mix insulin for added convenience

    • Is he carrying his insulin when he is out?

      • The insulin he is currently using can be out of refrigeration for 30 days

    • Referral to Endocrinologist for U-500 insulin


    Diabetes management is complicated

    Diabetes Management is Complicated…

    Nathan DM et al, Diabetes Care 2009;32:193-203


    Pearls for diabetes management

    Pearls for Diabetes Management

    • Listen to the patient’s experience

    • Think about options to make it more convenient/easier to deal with if possible

    • Use insulin earlier, or at least start talking about it before you need it

    • Remember to deal with cardiovascular risk factors in those with type 2 dm- they may be more critical than tight glucose control in the long run


    The end

    THE END


    When to consider adding insulin

    When to consider adding insulin?

    Those with symptoms of hyperglycemia, presence of ketonuria, persistent BG > 250-300mg/dl or A1c > 10%

    Those who have implemented lifestyle changes + metformin + second agent and are still not at goal

    Might consider adding a third oral agent if A1c < 8% but this approach is more costly and may be less effective

    Nathan DM et al, Diabetes Care 2006;29:1963


    Take home points

    Take Home Points

    • Most appropriate target for A1c is still < 7% to reduce risk of microvascular disease

      • Lower targets may be appropriate for SOME with diabetes (type 1?) but recognizing risks (hypoglycemia)

    • Emphasis on management of cardiovascular risk factors

      • Lipids, aspirin, blood pressure


    What to take away

    What to take away?

    • Both TZD’s are associated with fluid retention

      • Estimated as a 2-fold increase

      • Even greater with insulin use

    • Both also associated with increased risk of fracture, particularly in women

    • New labeling on package insert for rosiglitazone does not recommend use with insulin or in those using nitrates

    • Pioglitazone may have CV advantages

      • Better lipid effects and no evidence of more vascular events in Proactive Trial


    It vs ct in newly diagnosed type 2 dm

    IT vs CT in Newly Diagnosed Type 2 DM


    Intensive therapy in newly diagnosed type 2 dm

    Intensive Therapy in Newly Diagnosed Type 2 DM

    • 382 Chinese with newly diagnosed type 2 diabetes

      • Randomized to intensive therapy with either insulin injections (MDI), pump (CSII) or oral agents

      • Outcome included time to glycemic control and remission at 1 year

      • Mean age was 51 years, BMI 25.0, and mean fasting plasma glucose ….

      • Of these 23 treated with insulin and 13 with orals did not reach goals and 7 pts withdrew due to intolerance of metformin

        • These were withdrawn from further analysis

    Weng J et al, Lancet 2008;371:1753-60


    Results1

    Results

    • More achieved glucose control with insulin

      • 97.1% with CSII, 95.2% with MDI and 83.5% with orals

    • Time to glucose control was shorter with insulin

      • CSII: 4 days; MDI 5.6 days; orals 9.3 days

    • Remission rates also higher with insulin at one year

      • 51.1% with CSII and 44.9% with MDI vs 26.7% with orals

    • Acute insulin response was sustained with insulin groups but declined with orals


    Other data that adds to murk

    Other Data that adds to Murk…


    Initiation of insulin1

    Initiation of Insulin

    If A1c > 7% after 2-3 months

    If FBG in target range check pre-meal BG and depending on results add second injection

    Can usually start with ~ 4 units and adjust by 2 units every 3 days until in BG in range

    If pre-lunch high, add rapid-acting with breakfast; if pre-dinner high, add NPH at AM meal, or rapid-acting at lunch, if pre-bed high, add rapid-acting at dinner

    If A1c still elevated after 3 months of added therapy

    Recheck pre-meal BG levels to add another injection or may need to check post-prandial BG at 2 hours after eating and adjust

    Nathan DM et al, Diabetes Care 2009;32:193


  • Login