Basal Bolus: The Strategy for Managing All Diabetes

Fall, 2003

Paul Davidson, MD, FACE

Atlanta Diabetes Associates

Atlanta, Georgia

ACE / AACE Targets for Glycemic Control

HbA1c < 6.5 %

Fasting/preprandial glucose < 110 mg/dL

Postprandial glucose < 140 mg/dL

ACE / AACE Consensus Conference, Washington DC August 2001

Step Therapy

Diet

Exercise

Sulfonylurea or Metformin

Add Alternate Agent

Add hs NPH

Switch to Mixed Insulin bid

Switch to Multiple Dose Insulin

Utilitarian, Common Sense, RecommendedProne to Failure fromMisscheduling and Mismanagement

Stumble Therapy

YAG Diet

Golf Cart Exercise

Sample of the Week Medication

– Interupted,

– Not Combined

Poor Understanding of Goals

Poor Monitoring

HbA1c >8% (If Seen)

Informed Patient Refers Self Elsewhere

PETS TherapyStep--Spelled Backwards

All at once, nothing first, Just like bubbles, when they burst.

Start with Fast to Glucose <126 mg/dL

– Glargine, Wt x 0.1 units qd Feed PSMF Diet Add SU, MF, TZD, Repaglanide + prn Lispro for

BG <150 “Normal” BG from Day 1 Monitor BG qid See Patient Monthly, HFP HbA1c Bimonthly GI Problems: Cut MF

Hypoglycemia: Cut SUHypoglycemia Again: Cut RepaglinideAllow 2 Month to See TZD Effect

MIMICKING NATURE WITH INSULIN THERAPY

All persons need

both basal and mealtime insulin

to controlcontrol glucose

6-19

(endogenous or exogenous)

Limitations of NPH, Lente,and Ultralente

Do not mimic basal insulin profile

– Variable absorption

– Pronounced peaks

– Less than 24-hour duration of action

Cause unpredictable hypoglycemia

– Major factor limiting insulin adjustments

– More weight gain

1 5 10 15 20 25 30

1 5 10 15 20Asp

Gly

ArgExtension

Substitution

Arg

Insulin GlargineA New Long-Acting Insulin Analog

Modifications to human insulin chain

– Substitution of glycine at position A21

– Addition of 2 arginines at position B30

Gradual release from injection site

Peakless, long-lasting insulin profile

Glucose Infusion Raten = 20 T1DMMean ± SEM

SC insulin

4.0

3.0

2.0

1.0

0

24

20

16

12

8

4

0

0 4 8 12 16 20 24Time (hours)

mg

/kg

/min

µm

ol/k

g/m

in

Lepore M, et al. Diabetes. 2000;49:2142–2148.

NPH

Ultralente

Glargine

CSII

Lepore, et al. Diabetes. 1999;48(suppl 1):A97.

6

5

4

3

2

1

00 10

Time (h) after SC injection

End of observation period

20 30

GlargineNPH

Glu

cose

util

izat

ion

rate

(mg/

kg/h

)

Glargine vs NPH Insulin in Type 1 DiabetesAction Profiles by Glucose Clamp

Treat to Target Study: NPH vs Glargine in DM2 patients on OHA

Add 10 units Basal insulin at bedtime (NPH or Glargine)

Continue current oral agents Titrate insulin weekly to fasting BG < 100 mg/dL

• Based on average FBG of 6th and 7th day

- if 100-120 mg/dL, increase 2 units

- if 120-140 mg/dL, increase 4 units

- if 140-160 mg/dL, increase 6 units

- if 160-180 mg/dL, increase 8 units

The Treat-to-Target TrialRandomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patientsRiddle, Rosenstock, Gerich DIABETES CARE 2003 26;3080-2083

Percentage of Patients in Target (A1C < 7%)

2.5

32.3

48.8

66.2

58

0

10

20

30

40

50

60

70

Week 0 Week 8 Week 12 Week 18 Week 24

The Treat-to-Target TrialRandomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patientsRiddle, Rosenstock, Gerich DIABETES CARE 2003 26;3080-2083

GEMS--Glargine Evening Mealtime Secretagogue

Basal Dosing

– (Weight in #`s x 0.1)

• Glargine hs Prior to Meals

– Short Acting Secretagogue

• Rapaglinide 2 mg

• Nateglinide 120 mg

– Glimepiride 2 mg

The Treat-to-Target TrialRandomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patientsRiddle, Rosenstock, Gerich DIABETES CARE 2003 26;3080-2083

The Treat-to-Target TrialRandomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patientsRiddle, Rosenstock, Gerich DIABETES CARE 2003 26;3080-2083

The Treat-to-Target Trial . Bedtime Glargine vs NPH

With Mealtime Regular

4

3

2

1

0

48

36

24

12

0Nocturnal

HypoglycemiaWeight Gain

*

**

Wei

ght (

kg)

NPH Glargine

Patients (%

)

*P < .0007**P < .02 (compared to NPH)

Rosenstock, et al. Diabetes. 1999;48(suppl 1):A100.

6-52

Treatment to Target Study: NPH vs Glargine in DM2 patients on OHA

57% had HbA1c <7%

Nocturnal Hypoglycemia reduced by 42% in the Glargine group

33% had HbA1c <7% without any nighttime hypoglycemia in glargine group

Results significantly better than with NPH

Body Weight in pounds x 0.1

Average am BG x 2 after five days

Add to Glargine (BG-100)/10

Repeat weekly

Example: 200#

20 units glargine q hs

AM BG averages 200 on 6th and 7th day

Add (BG-100)10 to glargine,

i.e. increase to 20 to 30 units q hs

2nd week--average 130

increase glargine from 30 to 33

Establishing Basal Requirement for Glargine

Overall Summary: Glargine

Insulin glargine has the following

clinical benefits

– Once-daily dosing because of its prolonged duration of

action and smooth, peakless time-action profile

– Comparable or better glycemic control (FBG)

– Lower risk of nocturnal hypoglycemic events

– Safety profile similar to that of human insulin