Insulin Initiation :Benefit of Insulin Detemir in type 2 DM Management

Sony Wibisono M Surabaya Diabetes and Nutrition Center Dr. Soetomo Teaching Hospital, Faculty of Medicine Airlangga University, Surabaya

Outlines

Presentation structure Diabetes is a progressive disease and is increasing in prevalence The mapping of insulin treatment based recent guidelines Insulin Initiation, when we should start with basal insulin Insulin therapy in or outpatient in clinical practice Conclusion

Diabetes is a global disease

Estimated global prevalence of diabetes

171 million1 2000

1. 2.

366 million2 2011 2010

552 million2 2030

Wild. Diabetes Care. 2004. 27:1047-1053. International Diabetes Federation. IDF Diabetes Atlas. Fifth Edition. 2011

T2DM: Progressive loss of insulin secretion with increasing insulin resistance 1

Impaired glucose tolerance Undiagnosed diabetes Known diabetes

Insulin resistance

Insulin secretion Postprandial glucose Fasting glucose

Microvascular complications Macrovascular complications

1. Adapted from: Ramlo-Halsted BA, Edelman SV. Clincial Diabetes 2000;18(2): http://journal.diabetes.org/clinicaldiabetes/v18n22000/pg80.htm

Diabetes is a progressive disease

Type 2 diabetes (T2DM) progression is characterised by decline in beta-cell function and worsening insulin resistance1 Getting to, or maintaining, target HbA1c levels in T2DM requires intensified treatment over time2

1. 2.

Fonseca VA. Br J Diab Vasc Dis 2008;8:S3 Nathan DM, et al. Diabetes Care 2009;32:193-203

Diabetes being a progressive disease that is increasing in prevalence

T2DM results in a progressive loss of insulin secretion with increasing insulin resistance1 By 2030, IDF predicts 552 million people worldwide will have diabetes 2 Diabetes is the fourth most common diagnosed chronic condition 3 Many people with diabetes do not have good glycaemic control 3

1. 2. 3.

Ramlo-Halsted BA, Edelman SV. Clincial Diabetes 2000;18(2): http://journal.diabetes.org/clinicaldiabetes/v18n22000/pg80.htm International Diabetes Federation. IDF Diabetes Atlas. Fifth Edition. 2011 Brunton. Curr Med Res Opin 2011;2765-72

New position statement of the ADA and EASD on management of hyperglycemia in type 2 diabetes

Basal Insulin

Inzucci SE, et al. Diabetologia. 2012

New ADA/EASD Position on Sequential Insulin Strategy in Type 2 Diabetes

Non-Insulin Regimes
Basal Insulin Only Usually with OAD Basal Insulin + 1 mealtime rapid-acting injection Number of Injections Regimen Complexity

1 2 +3

Low

Pre-mixed Insulin twice-daily

Mod.

Basal Insulin + 2 mealtime rapid-acting injection More Flexible Less Convenient Less Flexible

High

Flexibility Convenience*

More Convenient

Inzucci SE, et al. Diabetologia. 2012. * Gumprecht et al. Intensification to to biphasic insulin aspart 30/70. Int J Clin Pract 2009

Patient Centered Approach

What is the optimal target HbA1c level?

EASD/ADA1 IDF2 EMA3
HbA1c <7.0% HbA1c <7.0% HbA1c <7.0%

Goals of optimum HbA1c levels: Good glycaemic control Minimise development and progression of microvascular and macrovascular complications
1. 2. 3. Inzucchi et al. Diabetes care. Published online 19Apr2012. IDF Treatment Algorithm. International Diabetes Federation 2011. http://www.idf.org/treatment-algorithm-people-type-2-diabetes EMA Draft guidance on clinical investigation in DM Jan 2010

Treat T2DM early for long-term benefits1

Long-term benefits in reducing cardiovascular risk can be achieved with good control from diagnosis1
50% of patients with T2DM with complications already have them at diagnosis2 Each HbA1c percentage point reduction counts3 -14% -37% -21%

Myocardial infarction Microvascular complications Death related to diabetes

HbA1c -1%
1. 2. 3. Holman, et al. NEJM 2008;359:157789 UKPDS 6. Diabetes Res 1990;13(1):1-11 Stratton, et al. BMJ 2000;321(7258):405-12

Insulin remains the most efficacious glucose lowering agent

Decrease in HbA1c: Potency of monotherapy

HbA1c %

CHOOSING INSULIN EARLIER FOR BETTER EFFICACY

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

Insulin can be initiated at any time

Traditionally, insulin has been reserved as the last line of therapy However, considering the benefits of normal glycemic status, Insulin can be initiated earlier and as soon as possible

Inadequate Lifestyle

+ 1 OAD

+ 2 OAD

+ 3 OAD

INITIATE INSULIN

How to start Basal Insulin

Start with basal insulin (Insulin Detemir) 10 U or 0,1-0,2 U per Kg BB Once daily injection, anytime injection but in same time per each day

Levemir Dose Titration Guidelines: 3-0-3 Algorithm

Start with Levemir 10 U or 0,1-0,2 U per Kg BB Simple Dose titration with Levemir
Mean 3-day FPG (mg/dL)
Increase FPG>90 mg/dl (5.0 mm/L) FPG target range 70-90 mg/dL 3units units Maintain dose Decrease 3 units FPG>110 mg/dL (6.1 mmol/L) FPG target range 80-110 mg/dL

FPG <70 mg/dL (3.8 mmol/L)

FPG <80 mg/dL (4.4 mmol/L)

Patients who experienced hypoglycemia reduced their daily dose by 3 units

Blonde L et al. Diabetes Obes Metab. 2009; 11(6):623-631.

Levemir/Glargine Head-to-Head: Similar Profiles in Type 2 Diabetes

3.0
Glucose infusion rate Insulin detemir Insulin glargine 0.4 U/kg 0.8 U/kg

2.5
(mg/kg/min)

2.0 1.5 1.0 0.5 0 0 2

10

12

14

16

18

20

22

24

Time (h)
Klein O et al. Diab Obes Metab 2007; 9:290-299

Levemir reduces nocturnal hypoglycaemia by up to 65% compared to NPH

NPH vs. glargine
-29% -44%

NPH vs. detemir

-53% -65%

Relative Risk

Insulin Determir Insulin NPH Insulin glargine

Riddle et al., 2003

Phillis-Tsimikas et al., 2006

Phillis-Tsimikas. Clin Ther 2006;28(10):156981; Riddle et al 2003. Diabetes Care; 26 (11): 30806; Asakura T et al, 2008. Expert Opin Pharmacother; 10 (9): 1-5; Hanel H et al 2008. J Diabetes Sci Technol; 2 (3): 478-81

A1chieve study overview and design

Observational study of people with T2DM in routine clinical practice
Start a study insulin
Biphasic insulin aspart 30 Insulin detemir Insulin aspart

BASELINE Week 0

INTERIM Week 12

FINAL Week 24

Study objectives
Primary: number of attributed adverse drug reactions (includes major hypoglycaemia) Secondary: other safety and effectiveness measures

Levemir OAD:
HbA1c (%)
9.5 147 Baseline values n

Indonesia efficacy results

Insulin nave
FPG (mg/dl)
219 317

PPG (mg/dl)
263 295

0.0

-80

Change from baseline to week 24

-1.0 -100 -2.0

-2.2* -101*

-3.0

-120
*p<0.001

-115*

Levemir OAD:
Overall
Insulin nave No. of pt w/hypo
6,0 5,10

Indonesia hypoglycaemia results

Major
Insulin nave 1 0
4,80

Nocturnal
Insulin nave 18 0

Baseline 24 weeks

19

Percent with at least one event

5,0 4,0 3,0 2,0 1,0 0,0

0,00

0,30

0,00

0,00

A1chieve: Self-rated health in insulin naive patients (Levemir)

Patients on Best imaginable Levemir health 100 90 80 70 60 50 40 30 20 10 0
Baseline 24 weeks

24 weeks Baseline

Worst imaginable health

Physiologic insulin secretion

Analogue insulin mechanisme of action

-------

Insulin endogen Levemir NovoRapid NovoMix

Breakfast

Lunch

Dinner

Bed time

HYPERGLYCAEMIA >200 mg/dl, EXAMPLE : 680 mg/dl

FORMULA FORMULA X2. X2. MT MT FOR SGC AND MAINTENANCE S.C. DOSE

SUBCUTANEOUS GLYCEMIC CONTROL (SGC)

(Clinical Experiencies : Tjokroprawiro 1987-2013) BASELINE GLUCOSE

Before SGC (mg/dl)

680 2 3 4 5 6 00 - 300 00 - 400 00 - 500 00 - 600 00 - 700

Subcutaneous (S.C.) Injection in unit

EXAMPLE : HYPERGLYCEMIA 680 mg/dl APIDRA DOSE (S.C.): FORMULA X2.MT 6 X2 = 12 UNITS APIDRA for TOMMOROW : 3 X 12 U

NOVORAPID DOSE

4 6 8 10 12

RGC

FORMULA X2. MT 6 X2 = 12

MT = MAINTENANCE

APIDRA : Onset 5-15 Mins; Peak 1-2 Hrs; Duration 3-4 Hrs

CTOI with FORMULA 1/3 for DISCHARGED-PATIENTS

(Clinical Experiences : Tjokroprawiro 2007-2013)

1 INPATIENTS TREATED with APIDRA 3x 20 Units per Day: Total dose of NOVORAPID 60 units per Day USE FORMULA 1/3 METHOD- A OR B
METHOD- A METHOD- B
- LEVEMIR : 20 units (1/3 of 60) Mornings - NOVORAPID : Formula X2 - SU : Mornings, or Mornings and Evenings -LEVEMIR : 20 units Evenings - NOVORAPID : Formula X2 - SU : Mornings, or Mornings and Evenings

or

PERKENI-CONSENSUS 2006 : Insulin Dose > 30 Units/day in CTOI

is not Recommended STOP OAD, and Give PREMIX Twice Daily (ADA/EASD-2012)

Continued

16

CTOI with FORMULA 1/3 for DIABETIC-OUTPATIENTS

(Clinical Experiences : Tjokroprawiro 2007-2013)

DIABETIC OUTPATIENTS FAILED with 2-4 OADs :

depending on 1-h PG (One Hour Plasma Glucose) , and Special attention to the figures of the first two fe. : 1-h PG 450 mg/dL , the First two is 45

FORMULA 1/3 (based on the figures of the first two , that is 45):
Thus, the Initial Dose : 1/3 of 45 = 15 Units METHOD- A
- LEVEMIR : 15 Units Mornings (At the Same Time of the Day) - NOVORAPID : Formula X2 - SU : Mornings, or Mornings and Evenings - LAVEMIR : 15 units Evenings (At the Same Time of the Day) - NOVORAPID : Formula X2 - SU : Mornings, or Mornings and Evenings

or

METHOD- B

FORMULAS : 1/3 , STEP-UP : 3-3-5 , STEP-DOWN : 2-2 , 2-1 , 1-2 , 1-1

(Clinical Experiences : Tjokroprawiro 2003-2013)
I STEP-UP FORMULA 3-3-5 WITH LEVEMIR

THE 1st 3 INDICATES DAY , whereas the 2nd & 3rd 3 & 5 INDICATE LEVEMIR DOSE
INCREASING INSULIN DOSE (3 or 5 units) after 3 DAY-EVALUATION 3 Units Increase if Pre Prandial PG (Morning-Glucose) : 130-200 mg/dL 5 Units Increase if Pre Prandial PG (Morning-Glucose) : > 200 mg/dL

II

INJECTION STEP-DOWN FORMULAS TO END LEVEMIR st

THE 1 FIGURE ( 2 or 1 ) INDICATES DAY , whereas : THE 2nd FIGURE ( 2 or 1 ) INDICATES DECREASE in LEVEMIR DOSE Every 2 Days 2 U Decrease , until LEVEMIR INJECTION OFF FORMULA 2-2 :
FORMULA 2-1 : FORMULA 1-2 : FORMULA 1-1 : Every 2 Days 1 U Decrease , Every Day 2 U Decrease , Every Day 1 U Decrease , until LEVEMIR OFF until LANTUS OFF until LANTUS OFF

APIDRA FORMULA for STEROID TREATED DM-Pts

FORMULA MP-25.4 and DEX-4.4
(Clinical Experiences: Tjokroprawiro 2010-2013)
1 Flacon 2 ml : 125 mg MP. Diluted with 3 ml NaCl 0.9% 5 ml with 125 MP . Thus : 1 ml Contains 25 mg MP

FORMULA MP-25.4 1 INTRAVENA METHYL PREDNISOLONE (MP) 25 mg : INTRAVENA METHYL PREDNISOLONE (MP) 25 mg : SC This 25 mg MP SHOULD be BACKED UP with 4 units APIDRA IV Every 25 mg MP SHOULD be BACKED UP with 4 units NOVORAPID SC or IV 2
3
METHYL PREDNISOLONE (MP) 50 mg : with 8 units Novorapid SC or IV
METHYL PREDNISOLONE (MP) 125 mg : with 20 units Novorapid SC / IV / PUMP

FORMULA DEX-4.4
1 2 3
SC SC INTRAVENA APIDRA or IV INTRAVENA DEXAMETHASON DEXAMETHASON(DEX) (DEX)44mg mg: :BACKED BACKEDUP UPwith with44units units Novorapid or IV

INTRAVENA DEXAMETHASON (DEX) 8 mg : BACKED UP with 8 units Novorapid SC or IV INTRAVENA DEXAMETHASON (DEX) 16 mg : BACKED UP with 16 units Novorapid SC / IV

Conclusion
Diabetes is a progressive disease that is increasing in prevalence in the world Starting with basal insulin detemir is easy way to reach better glycemic control In Indonesia, in real life clinical practice (A1chieve study) Levemir show significant improvements in overall glycaemic control in terms of HbA1c, FPG and PPG. Premixed insulin NovoMix is one option for insulin intensification, provide simple and convenient for patients

Thank You