diabetes medication: initiation and intensification gregory a. nichols, phd annual collaborative...

DiabetesDiabetes Medication: Medication: Initiation and IntensificationInitiation and Intensification

Gregory A. Nichols, PhDGregory A. Nichols, PhD

Annual Collaborative Diabetes Education Conference Annual Collaborative Diabetes Education Conference

for Health Professionalsfor Health Professionals

January 21, 2012January 21, 2012

DisclosuresDisclosures• Employed by Kaiser Permanente Center for Health Research, Portland, Employed by Kaiser Permanente Center for Health Research, Portland,

OregonOregon

• Government Research Funding:Government Research Funding:– National Institute of Diabetes and Digestive and Kidney Disorders (NIDDK)National Institute of Diabetes and Digestive and Kidney Disorders (NIDDK)

– National Heart, Lung and Blood Institute (NHLBI)National Heart, Lung and Blood Institute (NHLBI)

– Agency for Healthcare Research and Quality (AHRQ)Agency for Healthcare Research and Quality (AHRQ)

• Industry Funding:Industry Funding:

– GlaxoSmithKlineGlaxoSmithKline

– Merck & Co.Merck & Co.

– Novartis PharmaceuticalsNovartis Pharmaceuticals

– Tethys BioscienceTethys Bioscience

– Takeda Pharmaceuticals AmericaTakeda Pharmaceuticals America

– Novo NordiskNovo Nordisk

– AstraZenecaAstraZeneca

– AmgenAmgen

The Need for Diabetes The Need for Diabetes PharmacotherapyPharmacotherapy

• Diabetes is a metabolic condition Diabetes is a metabolic condition characterized by hyperglycemiacharacterized by hyperglycemia

– Insulin ResistanceInsulin Resistance

– Insufficient insulin productionInsufficient insulin production

• Progressive, typically requiring ongoing Progressive, typically requiring ongoing therapy intensificationtherapy intensification

General Benefits of MetforminGeneral Benefits of Metformin

• Reduces hepatic glucose production in the Reduces hepatic glucose production in the presence of insulinpresence of insulin

• At least weight neutralAt least weight neutral

• May be cardioprotectiveMay be cardioprotective

• May reduce cancer riskMay reduce cancer risk

• Definitely prevents/delays diabetes in some Definitely prevents/delays diabetes in some at-risk individualsat-risk individuals

Metformin Initiation at Metformin Initiation at Diabetes DiagnosisDiabetes Diagnosis

• Recommended by EASD/ADARecommended by EASD/ADA

• Does early vs. late metformin initiation and Does early vs. late metformin initiation and more intensive dosing:more intensive dosing:

– Increase the likelihood of successful metformin Increase the likelihood of successful metformin therapy?therapy?

– Prolong its success?Prolong its success?

Study Site and Sample SelectionStudy Site and Sample Selection

• Kaiser Permanente NorthwestKaiser Permanente Northwest

• All All diabetesdiabetes patients who initiated metformin patients who initiated metformin monotherapy as first-ever anti-hyperglycemic monotherapy as first-ever anti-hyperglycemic drug, 2004-2006drug, 2004-2006

• Members for > 1 year pre- and 6 months post-Members for > 1 year pre- and 6 months post-metformin initiation metformin initiation

• HbA1c measured pre- and post-metformin HbA1c measured pre- and post-metformin initiation initiation

Study Samplen = 3,116


Primary Failure or Non-Adherencen = 518 (16.6%)

Continued Metformin

n = 2,598 (83.4%)



Continued Metformin

n = 2,598 (83.4%)

No Refills, n=210

< 90 Days Supply, n=289

Added 2nd Agent, n=19



Continued Metformin

n = 2,598 (83.4%)

No Refills, n=210



A1C Measured 6 Months Post-Metformin

n = 2,508



Continued Metformin

n = 2,598 (83.4%)

No Refills, n=210




n = 2,508

Never Achieved <7%n = 709 (28.3%)

Achieved < 7%n = 1,799 (71.7%)

Characteristics of Patients Who Did Characteristics of Patients Who Did and Did Not Achieve A1C < 7%and Did Not Achieve A1C < 7%

Did Not Did Not Achieve < 7%Achieve < 7%

Achieved Achieved A1C < 7%A1C < 7%

P valueP value

Age at Metformin InitiationAge at Metformin Initiation 55.255.2 58.658.6 <0.001<0.001

Duration of Diabetes (years)Duration of Diabetes (years) 2.42.4 2.02.0 <0.001<0.001

% Men% Men 52.6%52.6% 48.4%48.4% 0.0590.059

Body Mass IndexBody Mass Index 36.736.7 35.635.6 0.0020.002

Adapted from Nichols et al. Curr Med Res Opin 2010;26:2127-2135

Characteristics of Patients Who Did Characteristics of Patients Who Did and Did Not Achieve A1C < 7%and Did Not Achieve A1C < 7%

Did Not Did Not Achieve < 7%Achieve < 7%


P valueP value

A1C at InitiationA1C at Initiation 8.9%8.9% 8.1%8.1% <0.001<0.001

Months to 7% or Lowest A1CMonths to 7% or Lowest A1C 9.29.2 6.36.3 <0.001<0.001

Dose When A1C < 7% Dose When A1C < 7% (or last dose)(or last dose)

1,7451,745 1,2831,283 <0.001<0.001

Medicine Possession RatioMedicine Possession Ratio 64.2%64.2% 88.0%88.0% <0.001<0.001


Factors Associated with Probability Factors Associated with Probability of Attaining A1C < 7%of Attaining A1C < 7%

Odds RatioOdds Ratio 95% CI95% CI P valueP value

Age at Initiation (per year)Age at Initiation (per year) 1.021.02 1.01 – 1.031.01 – 1.03 <0.001<0.001

BMI (per kg/mBMI (per kg/m22)) 0.980.98 0.97 – 0.990.97 – 0.99 0.0100.010

Initial Dose > 1000mgInitial Dose > 1000mg 1.711.71 1.33 – 2.201.33 – 2.20 0.0040.004

MPR MPR >> 80% 80% 4.594.59 3.60 – 5.853.60 – 5.85 <0.001<0.001


A1C at Metformin Initiation and A1C at Metformin Initiation and Probability of Attaining A1C < 7%*Probability of Attaining A1C < 7%*

A1C at InitiationA1C at Initiation Odds RatioOdds Ratio 95% CI95% CI P valueP value

< 7.0% (n=522)< 7.0% (n=522) 6.816.81 4.56 – 10.24.56 – 10.2 <0.001<0.001

7 – 7.9% (n=840)7 – 7.9% (n=840) 1.671.67 1.27 – 2.191.27 – 2.19 <0.001<0.001

8 – 8.9% (n=455)8 – 8.9% (n=455) refref ---- ----

> 9.0% (n=691)> 9.0% (n=691) 0.670.67 0.50 – 0.880.50 – 0.88 0.0050.005

*Controlling for age, BMI, Initial Dose, MPR, and duration of diabetes at initiation


Best A1C Achieved by Best A1C Achieved by A1C at Metformin InitiationA1C at Metformin Initiation

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

< 7% (n=522) 7 - 7.9% (n=840) 8 - 8.9% (n=455) > 9% (n=691)

A1C at Metformin Initiation

> 9%8-8.9%7-7.9%6-6.9< 6%

Best HbA1c

Diabetes Duration and Probability of Diabetes Duration and Probability of Attaining A1C < 7%*Attaining A1C < 7%*

Duration of DiabetesDuration of Diabetes Odds RatioOdds Ratio 95% CI95% CI P valueP value

0–3 Months (n=935)0–3 Months (n=935) 2.852.85 2.04 – 3.982.04 – 3.98 <0.001<0.001

4–11 Months (n=262)4–11 Months (n=262) 1.731.73 1.13 – 2.641.13 – 2.64 0.0110.011

12–23 Months (n=335)12–23 Months (n=335) refref ---- ----

24–35 Months (n=281)24–35 Months (n=281) 1.101.10 0.74 – 1.630.74 – 1.63 0.6300.630

>> 36 Months (n=695) 36 Months (n=695) 0.820.82 0.60 – 1.140.60 – 1.14 0.2340.234

*Controlling for age, BMI, Initial Dose, MPR, and A1C at initiation


Best A1C Achieved by Diabetes Best A1C Achieved by Diabetes Duration at Metformin InitiationDuration at Metformin Initiation

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

0-3 Months(n=935)

4-11 Months(n=262)

12-23 Months(n=335)

24-35 Months(n=281)

36+ Months(n=695)

Duration of Diabetes at Metformin Initiation

> 9%8-8.9%7-7.9%6-6.9< 6%

Best HbA1c




Continued Metformin

n = 2,598 (83.4%)

No Refills, n=210




n = 2,508


Achieved < 7%n = 1,799 (71.7%)

Definitions of Secondary FailureDefinitions of Secondary Failure

• Added/switched to another anti-Added/switched to another anti-hyperglycemic agenthyperglycemic agent

• Subsequent HbA1c Subsequent HbA1c >> 7.5% 7.5%

• Composite of the aboveComposite of the above



Continued Metformin

n = 2,598 (83.4%)

No Refills, n=210




n = 2,508


Achieved < 7%n = 1,799 (71.7%)

Secondary Failuren = 748 (41.6%)

Continued SuccessN = 1,051 (58.4%)

Sample CharacteristicsSample Characteristics

Failed Failed MetforminMetformin Did Not FailDid Not Fail P valueP value

N N

(%)(%)

748 748

(41.6%)(41.6%)

1,051 1,051

(58.4%)(58.4%) ----

Age in YearsAge in Years 57.757.7 59.259.2 0.0080.008

% Men% Men 50.0%50.0% 47.3%47.3% 0.2570.257

Duration of Diabetes at Duration of Diabetes at Metformin Initiation, MonthsMetformin Initiation, Months

26.526.5 21.421.4 <0.001<0.001

HbA1c at Metformin InitiationHbA1c at Metformin Initiation 8.2%8.2% 7.9%7.9% <0.001<0.001

Months to Failure or End of Months to Failure or End of Follow-upFollow-up

16.916.9 27.627.6 <0.001<0.001

Adapted from Brown et al. Diabetes Care 2010;33:501-506

Probability of Secondary FailureProbability of Secondary Failure

Odds Ratio 95% CI p value

Age at metformin initiation (per year) 0.98 0.97 - 0.99 <0.001

Duration of Diabetes at Metformin Initiation:

0 - 3 Months (reference) 1.00 -- --

4 - 11 Months 1.56 1.12 - 2.18 0.008

12 - 23 Months 2.09 1.53 - 2.87 <0.001

24 - 35 Months 1.59 1.13 - 2.24 0.007

> 36 Months 2.20 1.68 - 2.87 <0.001

HbA1c prior to metformin:

< 7% (reference) 1.00 -- --

7 - 7.9% 1.53 1.19 - 1.98 0.001

8 - 8.9% 1.73 1.27 - 2.35 <0.001

> 9.0% 2.04 1.54 - 2.72 <0.001


Secondary Failure of Metformin by Secondary Failure of Metformin by HbA1c at InitiationHbA1c at Initiation

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

Months on Metformin

Pro

po

rtio

n N

ot

Exp

eri

en

cin

g S

eco

nd

ary

Fail

ure

< 7%

7-7.9%8-8.9%

> 9%

< 7%12.3%/year(10.5-14.4)

7-7.9%17.8%/year(15.7-20.1)

8-8.9%19.2%/year(16.2-22.8)

>= 9.0%19.4%/year(16.8-22.4)


Secondary Failure of Metformin by Secondary Failure of Metformin by Diabetes Duration at InitiationDiabetes Duration at Initiation

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

Months on Metformin

Pro

po

rtio

n N

ot

Ex

pe

rie

nc

ing

Se

co

nd

ary

Fa

ilu

re

0-3 Months4-11 Months12-23 Months24-35 Months> 36 Months

0-3 Months12.2%/year(10.5-14.4)

4-11 Months17.8%/year(15.7-20.1)12-23 Months

21.4%/year(17.8-25.8)

24-35 Months18.4%/year(14.7-22.9)

>=36 Months21.9%/year(19.1-25.1)


SummarySummary

• In KPNW clinical practice, 72% of drug In KPNW clinical practice, 72% of drug naïve patients attained the goal of A1C<7% naïve patients attained the goal of A1C<7%

• After attaining goal, metformin After attaining goal, metformin monotherapy secondary failure rates are monotherapy secondary failure rates are highhigh

• But…But…

SummarySummary

• Initiation at diagnosis greatly improves Initiation at diagnosis greatly improves chances of achieving A1C < 7%chances of achieving A1C < 7%

• Patients who initiate metformin at diagnosis Patients who initiate metformin at diagnosis and attain A1C < 7% remain in good and attain A1C < 7% remain in good glycemic control for longer periods than glycemic control for longer periods than those who delay initiationthose who delay initiation

• Achieving good control with metformin is Achieving good control with metformin is possible even in patients with relatively high possible even in patients with relatively high pre-therapy A1Cpre-therapy A1C

ConclusionsConclusions

• The EASD/ADA recommends initiating The EASD/ADA recommends initiating metformin when diabetes is diagnosed metformin when diabetes is diagnosed

• The KPNW experience confirms the The KPNW experience confirms the wisdom of that recommendationwisdom of that recommendation

• Simultaneous lifestyle changes should also Simultaneous lifestyle changes should also be initiated at diagnosis, but exercise may be initiated at diagnosis, but exercise may reduce metformin effectivenessreduce metformin effectiveness

SulphonylureasSulphonylureas

• Been around since 1954Been around since 1954

• Enhance beta cell production by allowing Enhance beta cell production by allowing release of insulin at lower glucose levelsrelease of insulin at lower glucose levels

• May cause weight gainMay cause weight gain

• More likely to cause hypoglycemiaMore likely to cause hypoglycemia

• Have been associated with cardiovascular Have been associated with cardiovascular diseasedisease



• Diabetes patients who initiated SU (glyburide) Diabetes patients who initiated SU (glyburide) monotherapy as first-ever anti-hyperglycemic monotherapy as first-ever anti-hyperglycemic drugdrug

• Members for > 1 year pre- and post-SU initiation Members for > 1 year pre- and post-SU initiation

• Therapeutic success defined as achievement of Therapeutic success defined as achievement of A1C < 8%A1C < 8%

• Failure defined as subsequent A1C Failure defined as subsequent A1C >> 8% 8%

Characteristics Associated with Characteristics Associated with Initial Success of SUsInitial Success of SUs

Achieved Achieved

A1C < 8%A1C < 8%

Did Not Did Not

Achieve 8%Achieve 8% P valueP value

N (%)N (%) 4,091 (89.9%)4,091 (89.9%) 462 (11.1%)462 (11.1%) ----

AgeAge 60.360.3 55.455.4 <0.001<0.001

A1C prior to SUA1C prior to SU 9.2%9.2% 10.4%10.4% <0.001<0.001

1 Year Weight Change 1 Year Weight Change with SU (kg)with SU (kg)

-0.02-0.02 1.011.01 <0.001<0.001

Initial Dose (mg)Initial Dose (mg) 3.73.7 4.64.6 <0.001<0.001

Last Dose (mg)Last Dose (mg) 5.05.0 7.87.8 <0.001<0.001

Adapted from Nichols et al. Endocr Pract 2007;13:37-44

Characteristics Associated with Characteristics Associated with Secondary Failure of SUsSecondary Failure of SUs

Subsequent Subsequent

A1C >= 8%A1C >= 8%

A1C Never A1C Never

>= 8%>= 8% P valueP value

N (%)N (%) 1,769 (43.2%)1,769 (43.2%) 2,322 (56.8%)2,322 (56.8%) ----

AgeAge 58.958.9 61.661.6 <0.001<0.001

A1C prior to SUA1C prior to SU 9.6%9.6% 8.9%8.9% <0.001<0.001

Diabetes Duration at Diabetes Duration at SU Initiation (months)SU Initiation (months)

11.611.6 14.814.8 0.0110.011

Months of follow-upMonths of follow-up 24.824.8 39.139.1 <0.001<0.001

Dose Dose >> 10mg 10mg 56.6%56.6% 21.5%21.5% <0.001<0.001


A1C Prior to Initiation and A1C Prior to Initiation and Secondary Failure of SUsSecondary Failure of SUs

Hazard RatioHazard Ratio 95% CI95% CI P valueP value

< 7.0%< 7.0% 1.001.00 ---- ----

7.0 – 7.9%7.0 – 7.9% 1.251.25 0.93 – 1.670.93 – 1.67 0.1350.135

8.0 – 8.9%8.0 – 8.9% 1.501.50 1.13 – 1.991.13 – 1.99 0.0050.005

>> 9.0% 9.0% 1.811.81 1.37 – 2.381.37 – 2.38 <0.001<0.001


Time to A1C > 8% by A1C Time to A1C > 8% by A1C Achievement with SUsAchievement with SUs


Summary and Conclusions (SUs)Summary and Conclusions (SUs)

• Patients are highly responsive to SU’sPatients are highly responsive to SU’s

• Initiation of SU’s at lower A1C levels Initiation of SU’s at lower A1C levels increases likelihood and durability of increases likelihood and durability of responseresponse

• SU’s fail faster when A1C reductions are SU’s fail faster when A1C reductions are smallersmaller

Metformin/Sulphonylurea Metformin/Sulphonylurea Combination TherapyCombination Therapy

• Typically initiated by adding one agent to Typically initiated by adding one agent to the other—rarely initiated simultaneouslythe other—rarely initiated simultaneously

• Despite different mechanisms of action, Despite different mechanisms of action, glycemic benefits aren’t additiveglycemic benefits aren’t additive

• Durability of 2Durability of 2ndnd agent less than when agent less than when initiated as 1initiated as 1stst agent agent

• Some evidence that the combination raises Some evidence that the combination raises CVD riskCVD risk



• Diabetes patients who initiated SU/metformin Diabetes patients who initiated SU/metformin combination therapy (SU/MET)combination therapy (SU/MET)

• Members for > 6 months pre- and post-SU/MET Members for > 6 months pre- and post-SU/MET initiation initiation

• Therapeutic success defined as achievement of Therapeutic success defined as achievement of A1C < 8%A1C < 8%

• Time to insulin initiation when A1C Time to insulin initiation when A1C >> 8% 8%

Patient Characteristics by Whether Patient Characteristics by Whether A1C < 8% was Attained or A1C < 8% was Attained or Maintained with SU/METMaintained with SU/MET

Maintained Maintained < 8%< 8%

Attained, Did Attained, Did not Maintain not Maintain

< 8%< 8%Never Never

Attained < 8%Attained < 8%

N (%)N (%) 944 (24.3%)944 (24.3%) 2,241 (57.6%)2,241 (57.6%) 706 (18.1%)706 (18.1%)

Age at SU/MET InitiationAge at SU/MET Initiation 61.961.9 59.259.2 53.853.8

Last SU DoseLast SU Dose 11.311.3 13.813.8 14.414.4

Last Metformin DoseLast Metformin Dose 1,6751,675 1,9131,913 1,8651,865

SU MPRSU MPR 0.790.79 0.820.82 0.810.81

Metformin MPRMetformin MPR 0.780.78 0.750.75 0.700.70Adapted from Nichols et al. J Gen Intern Med 2007;22:453-458

Glycemic History by Whether Glycemic History by Whether A1C < 8% was Attained or A1C < 8% was Attained or Maintained with SU/METMaintained with SU/MET

Maintained Maintained < 8%< 8%

Attained, Did Attained, Did not Maintain not Maintain

< 8%< 8%Never Never

Attained < 8%Attained < 8%

A1C Prior to SU/MetA1C Prior to SU/Met 8.9%8.9% 9.1%9.1% 10.3%10.3%

Best A1C on SU/MetBest A1C on SU/Met 6.3%6.3% 6.7%6.7% 9.2%9.2%

Mean A1C on SU/MetMean A1C on SU/Met 7.2%7.2% 8.1%8.1% 10.0%10.0%

Months on SU/MetMonths on SU/Met 54.954.9 62.162.1 30.130.1

Months A1C < 8%Months A1C < 8% 44.644.6 17.117.1 00

Glycemic BurdenGlycemic Burden 11.111.1 31.831.8 63.963.9Adapted from Nichols et al. J Gen Intern Med 2007;22:453-458

Time to Insulin Addition on SU/METTime to Insulin Addition on SU/MET

Nichols et al. J Gen Intern Med 2007;22:453-458

Summary and Conclusions Summary and Conclusions (SU/MET)(SU/MET)

• SU/MET works for most patients, but not SU/MET works for most patients, but not for longfor long

• Most patients on SU/MET delay adding Most patients on SU/MET delay adding insulin for WAY too long, incurring insulin for WAY too long, incurring tremendous glycemic burdentremendous glycemic burden

InsulinInsulin

• A question of when (not if) A question of when (not if)

• Can theoretically lower any level of A1CCan theoretically lower any level of A1C

• Causes weight gainCauses weight gain

• HypoglycemiaHypoglycemia

• Has been associated with heart failureHas been associated with heart failure

• ““Psychological Insulin Resistance”Psychological Insulin Resistance”



• Diabetes patients who newly initiated insulin Diabetes patients who newly initiated insulin therapytherapy

• Members for > 1 year pre- and 270 days post Members for > 1 year pre- and 270 days post insulin initiation insulin initiation

• Early response defined as achievement of A1C < Early response defined as achievement of A1C < 7% at first measurement within 90-270 days7% at first measurement within 90-270 days

Characteristics Associated with Early Characteristics Associated with Early Glycemic Response to InsulinGlycemic Response to Insulin


Did Not Did Not Achieve <7%Achieve <7%

P P

valuevalue

N (%)N (%) 464 (40.7%)464 (40.7%) 675 (59.3%)675 (59.3%) ----

Mean AgeMean Age 66.166.1 62.662.6 <0.001<0.001

Duration of DiabetesDuration of Diabetes 8.58.5 9.09.0 0.0500.050

Long-Acting Insulin OnlyLong-Acting Insulin Only 24.1%24.1% 39.6%39.6% <0.001<0.001

Short-Acting Insulin OnlyShort-Acting Insulin Only 19.2%19.2% 5.6%5.6% <0.001<0.001

Long- and Short-Acting InsulinLong- and Short-Acting Insulin 56.7%56.7% 54.8%54.8% 0.0430.043

Concomitant Oral AgentsConcomitant Oral Agents 67.2%67.2% 73.0%73.0% 0.0350.035

Adapted from Nichols et al. Diabetes Care (submitted)

Characteristics Associated with Early Characteristics Associated with Early Glycemic Response to with InsulinGlycemic Response to with Insulin


Did Not Did Not Achieve <7%Achieve <7%

P P

valuevalue

A1C Prior to InsulinA1C Prior to Insulin 8.2%8.2% 9.2%9.2% <0.001<0.001

11stst A1C 90 Days Post-Insulin A1C 90 Days Post-Insulin 6.3%6.3% 8.0%8.0% <0.001<0.001

Change in A1CChange in A1C 1.9%1.9% 1.2%1.2% <0.001<0.001

Units per DayUnits per Day 47.447.4 53.253.2 <0.001<0.001


Probability of Early Probability of Early Glycemic Response to InsulinGlycemic Response to Insulin

Odds RatioOdds Ratio 95% CI95% CI P valueP value

Long-Acting Insulin OnlyLong-Acting Insulin Only 1.001.00 ---- ----

Short-Acting Insulin OnlyShort-Acting Insulin Only 3.133.13 1.96-5.011.96-5.01 <0.001<0.001

Long- and Short-Acting InsulinLong- and Short-Acting Insulin 2.042.04 1.53-2.741.53-2.74 <0.001<0.001

Pre-Insulin A1CPre-Insulin A1C 0.740.74 0.68-0.800.68-0.80 <0.001<0.001

Diabetes DurationDiabetes Duration 0.960.96 0.94-0.990.94-0.99 0.0070.007

Units per DayUnits per Day 0.990.99 0.98-1.000.98-1.00 0.0240.024

Concomitant Oral AgentsConcomitant Oral Agents 0.840.84 0.63-1.110.63-1.11 0.2080.208




• Diabetes patients who newly initiated insulin Diabetes patients who newly initiated insulin therapy (n=2,417)therapy (n=2,417)

• Members for > 1 year pre- and up to 7 years post Members for > 1 year pre- and up to 7 years post insulin initiation insulin initiation

• Glycemic response, usage and weight changes Glycemic response, usage and weight changes analyzed each quarter (90 days) post-insulinanalyzed each quarter (90 days) post-insulin

Glycemic Response to Insulin Glycemic Response to Insulin Over TimeOver Time

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

5.0%

6.0%

7.0%

8.0%

9.0%

10.0%

HbA1c < 7.0%

HbA1c 7-7.9%

HbA1c 8-8.9%

HbA1c > 9.0%

Nichols et al. Curr Med Res Opin 2010;26:9-15

Insulin Usage Over TimeInsulin Usage Over Time

40

50

60

70

80

90

100

110

Un

its p

er D

ay

70.0%

75.0%

80.0%

85.0%

90.0%

95.0%

100.0%

Percen

t w

ith

In

su

lin

Dis

pen

ses

Units/Day

% Purchasing Insulin


Change in Weight with InsulinChange in Weight with Insulin

-2

0

2

4

6

8

10

12

14

16

18

Qtr1

Qtr2

Qtr3

Qtr4

Qtr5

Qtr6

Qtr7

Qtr8

Qtr9

Qtr10

Qtr11

Qtr12

Qtr13

Qtr14

Qtr15

Qtr16

Qtr17

Qtr18

Qtr19

Qtr20

Qtr21

Qtr22

Qtr23

Qtr24

Qtr25

Qtr26

Qtr27

Qtr28

Ch

an

ge f

rom

Baseli

ne B

od

y W

eig

ht

in P

ou

nd

s

0.0%

10.0%

20.0%

30.0%

40.0%

50.0%

60.0%

Perc

en

t G

ain

ing

5%

of

Init

ial

Bo

dy W

eig

ht

Mean Change in Pounds

Proportion Gaining > 5% of Initial Weight


Summary and Conclusions (Insulin)Summary and Conclusions (Insulin)

• Initiation of insulin at lower levels of A1C Initiation of insulin at lower levels of A1C increases glycemic responseincreases glycemic response

• Ongoing dosage increases will probably be Ongoing dosage increases will probably be necessary to maintain glycemic controlnecessary to maintain glycemic control

• Weight gain occurs rapidly but levels offWeight gain occurs rapidly but levels off

Other Anti-HyperglycemicsOther Anti-Hyperglycemics

• Meglitinides (Starlix, Prandin)Meglitinides (Starlix, Prandin)

• Thiazolidinediones (Actos, Avandia)Thiazolidinediones (Actos, Avandia)

• ΑΑlpha-glucosidase Inhibitors (Precose, Glyset)lpha-glucosidase Inhibitors (Precose, Glyset)

• DPP-4 Inhibitors (Januvia, Onglyza)DPP-4 Inhibitors (Januvia, Onglyza)

• Pramlintide (Symlin)Pramlintide (Symlin)

• Incretin mimetics (Byetta)Incretin mimetics (Byetta)

Summary and ConclusionsSummary and Conclusions

• Early initiation of pharmacotherapy Early initiation of pharmacotherapy improves response to and durability of the improves response to and durability of the therapytherapy

• This pattern continues as therapy escalates This pattern continues as therapy escalates to oral combination and then insulinto oral combination and then insulin

• Adherence also plays a roleAdherence also plays a role

• Does minimizing cumulative glycemic Does minimizing cumulative glycemic burden reduce risk of complications?burden reduce risk of complications?

diabetes medication: initiation and intensification gregory a. nichols, phd annual collaborative...

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