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The importance of

Controlling and Monitoring


Blood Glucose Level to
Improve Diabetes Patient
Outcome
Estimated number of people with diabetes
worldwide and per region in 2015 and 2040
(20-79 years)

The prevalence of diabetes, of which type 2


diabetes predominates, is expected to rise
from 415 million in 2015 to 642 million by
2040

IDF Diabetes Atlas-Seventh Edition, 2015

Diabetes poses a huge economic burden to all nations, 75% of all cases
occur in low- and middle income countries (South-East Asia). If these
trends continue, by 2040 some 642 million people, or one adult in ten,
will have diabetes.
Diabetes by region
Number of people with diabetes
Region
2015 2040
Africa 14.2 million 34.2 million
Europe 59.8 million 71.1 million
Middle East and North Africa 35.4 million 72.1 million
North America and Caribbean 44.3 million 60.5 million

South and Central America 29.6 million 48.8 million


INDONESIA
South-East Asia 78 million 140 million
- Western
One ofPasific
the top ten countries in the world
153 million 215 million
- 10.0 million in 2015
Total Health Expenditure
Region
2015 2040
Africa 3.4 billion 5.5 billion
Europe 156 billion 174 billion
Middle East and North Africa 17.1 billion 31.0 billion
North America and Caribbean 348 billion 390 billion
South and Central America 34.6 billion 55.6 billion
People with diabetes are at increased risk
South-East Asia 7.3 billion 12.9 billion
for developing numerous complications,
resulting in increased health care costs Western Pasific 106 billion 133 billion
Intensive Diabetes Management Had Significant
Beneficial Effects on Cardiovascular-Related Deaths

Intensive diabetes management of


all risk factors, including elevated
lipids, blood pressure, and glycemia,
had significant beneficial effects on
cardiovascular-related deaths

Gaede P, Lund-Andersen H, Parving HH, Pedersen O. 2008


Intensive Diabetes Management Had Significant
Beneficial Effects on Cost-effective

QALE: Quality-adjusted life expectancy

Both treatment arms received their care in the same primary care setting,
intensive treatment was found to be dominant (cost- and life-saving) versus
conventional treatment

Gaede P, Valentine WJ, Palmer AJ, Tucker DM, Lammert M, Parving HH, Pedersen O. 2008
Importance of Addressing Postprandial
Hyperglycemia
Mechanisms by which Hyperglycemia May
Oxidative stress has been implicated as
Increase Risk For Macrovascular Disease the underlying cause of both the
macrovascular and microvascular
complications associated with T2DM

Addressing this metabolic abnormality


is particularly important because
postprandial hyperglycemia occurs
frequently in individuals with type 1
diabetes mellitus (T1DM) and T2DM.

DAG: Diacylglycerol
ET-1: Endothelial-1
NO: Nitric Oxide
PAI-1: Plasminogen Activator Inhibitor 1
PKC: Protein Kinase C

• Gerich JE. 2003


• Khatri JJ, Johnson C, Magid R, Lessner SM, Laude KM, Dikalov
SI, Harrison DG, Sung HJ, Rong Y, Galis ZS. 2004
Numerous studies support the hypothesis of a causal
relationship between hyperglycemia and oxidative stress
Value and Utility of Self-Monitoring of Blood Glucose
(SMBG)
SMBG is recognized as an important tool that guides glycemic management strategies and has the
potential to improve problem-solving and decision-making skills for both the person with diabetes
and his or her health care professional.

1. Fasting hyperglycemia

It can distinguish among: 2. Preprandial hyperglycemia

3. Postprandial hyperglycemia

Detec: Glycemic excursions


SMBG Identify and assist in monitoring: Resolution of hypoglycemia

Provide immediate feedback to 1. The effects of food choices


patients about:
2. Activity

3. Medication on glycemic control


Value and Questionable value
of Self-Monitoring of Blood Glucose (SMBG)

Value Questionable value


(SMBG+non-insulin-treated patients)

1. Metformin and insulin plus SMBG could A study by Farmer and colleagues
achieve a normal HbA1c in a period of just 3
SMBG months. (Lingvay I, Kaloyanova PF, Adams-Huet B, Salinas K,
(DIGEM):
There were no significant differences
Raskin P . 2007)
2. Important in managing diabetes during in improved HbA1c control among the 3
pregnancy (significantly benefits fetal groups (control , less intensive SMBG ,
outcomes). (Jovanovic LG .2008) intensive SMBG ). (Farmer A, Wade A, Goyder E,
Yudkin P, French D, Craven A, Holman R, Kinmonth AL, Neil A )

It has been suggested that failure to show benefit from SMBG-use in non–insulin-treated
diabetes in this study and others may stem from a misapplication or misunderstanding of
the true utility of SMBG as a tool to guide therapy, rather than as an independent therapeutic
intervention.
Klonoff DC. 2008
Parkin CG, Price D. 2007
Davidson MB, Castellanos M, Kain D, Duran P. 2005
Miles P, Everett J, Murphy J, Kerr D. 1997
Parkin CG, Hirsch IB. 2005
Proposed Criteria for Effective Use of SMBG
Although many studies have reported negative findings regarding SMBG use in non–insulin-treated
T2DM, simply demonstrated that SMBG is valuable only when it is used effectively.

Proposed Criteria for Effective Use of SMBG


(Parkin CG, Price D. 2007)

Use of SMBG may improve glycemic control in non–insulin-treated T2DM subjects when the
following criteria are met:
Subjects • Possess the knowledge and ability to accurately perform SMBG and accurately
interpret their testing data.
• Consistently use SMBG according to a prescribed regimen that facilitates detection of
patterns of glycemic control.
• Possess the knowledge and ability to make appropriate adjustments in their therapy.
• Consistently make appropriate adjustments as needed.
• Consistently and accurately record their test results and related events (manually or
electronically). If recorded electronically, the patient must ensure that the meter is
accurately programmed (time and date) and that accurate and complete event data
are entered.
Healthcare • Use therapies that adequately address all parameters of glycemic control
(fasting/preprandial and postprandial glucose).
Professionals • Possess the knowledge and ability to accurately interpret SMBG data.
(HCPs) • Possess the knowledge and ability to make timely and appropriate adjustments in
patient therapy.
• Consistently monitor patient SMBG results and make appropriate adjustments
Self-monitoring Blood Glucose Profile of a
Representative Patient With Type 2 Diabetes
For example, patients may use a 7-point SMBG regimen, testing before and after each meal and at
bedtime, over the course of 3 to 7 days. Or, patients may use a “staggered” regimen, testing before
and after alternating meals (e.g., pre- and post-breakfast on Monday, pre- and post-lunch on
Tuesday, etc.), over a 2- to 3-week period

Dailey G. 2007
Episodic, Intensive Use of SMBG

There are several situations in which intensive, episodic (short-term) SMBG can
be beneficial to this patient group. These situations include times when patients:

have symptoms of hypoglycemia;

are undergoing adjustment in medication, nutrition,


and/or physical activity;

experience worsening HbA1c values

The AACE recommends episodic, intensive monitoring by patients with T2DM as


a means to obtain comprehensive preprandial and 2-hour postprandial glucose
measurements periodically and before clinician visits to guide adjustments in
diabetes management.
Pattern Analysis: Effective Use of SMBG Data
Pattern analysis is a systematic approach to identifying glycemic patterns within
SMBG data and then taking appropriate action based upon those results

Using pattern analysis involves:

Establishing pre- and post-prandial glucose targets;

Obtaining data on glucose levels, carbohydrate intake, medication


administration (type, dosage, timing), activity levels, and
physical/emotional stress;

Analyzing data to identify patterns of glycemic excursions and


assessing any influential factors;

Implementing appropriate action(s);

Performing ongoing SMBG to assess the impact of any therapeutic


changes made
Pattern Management in Practice
The examples in Tables 1–3 translate the strategies into practice.

Pearson J,
Bergenstal R.
2001
Pattern Management in Practice
The examples in Tables 1–3 translate these strategies into practice.

Pearson J, Bergenstal R. 2001


SMBG Data Formats
SMBG Data formats offered by the software programs typically
include:

1. An “electronic logbook” that lists blood glucose readings by date


and time;

2. Statistical summaries of average blood glucose values, number of


tests performed, proportion of glucose levels above, below, and
within the target range, frequency of testing by day of the week,
and by time period within a given day, and the standard deviations,
indicating glycemic variability, for specified time periods.

3. One data management tool also provides information about patient


risk for hypoglycemia and hyperglycemia using blood glucose risk
indices
SMBG Data Formats
Information is also presented in histograms, pie charts, and a modal day/week (a
graphic that plots blood glucose values against a single 24-hour or 7-day period)

Day graph (modal day) from electronic data management tool .The graph
provides detailed information on the blood glucose values and helps define
the degree of glucose exposure and glucose variability over the reported time
period. The blue boxes represent the standard deviation on mean blood
glucose values, reflecting the glycemic variability.

Kovatchev BP, Cox DJ, Gonder-Frederick LA, Clarke W. 1997


Accu-Chek® 360° View blood glucose analysis system
New paper-based tools have also been developed to address clinical situations where computer-based pattern
analysis is not desirable or practical. One such tool, the Accu-Chek® 360° View blood glucose analysis system.
Patient Name Insulin Name Dose (Units) Shots.OAV Oral Diabetes Medication Dose Times/day Physician Name

Patient Name Physician Name


The form is used to
create a seven-
point glucose
profile over 3 days.

Space is provided
to plot and visualize
blood glucose
results.

Guidelines on the
form (rows
highlighted in
yellow) indicate
pre- or postprandial
blood glucose
target ranges and
ranges considered
too high or low.

Additional space is
provided at the
bottom to allow
individuals to
document what
they learned from
their testing.
ADA/EASD 2015: approach to starting
and adjusting insulin in T2DM

Basal insulin alone is the most convenient initial regimen,


beginning at 10 U or 0.1–0.2 U/kg, depending on the degree of
hyperglycemia. It is usually prescribed in conjunction with
metformin and possibly one additional non-insulin agent.
Once insulin is initiated, dose titration is important

ADA, American Diabetes Association;


EASD, European Association for the Study of Diabetes;
T2DM, type 2 diabetes mellitus Inzucchi SE, et al. Diabetes Care 2015;38:140–9.
Dose titration of insulin glargine
• The dose of insulin glargine should be adjusted according to
an individual’s metabolic needs and blood glucose
measurements to reach their glycemic control goal

• The dosage of insulin glargine should be individualized under


the supervision of a treating healthcare professional

Sanofi. LANTUS® (Insulin Glargine) Prescribing Information. USA, 2015.


Approach to Starting and Adjusting Insulin in Type 2 Diabetes
# Basal Insulin Compl exity
Inj (usually with metformin +/1 other non-insulin agent(s) Low
1
• Start: 10 U/day or 0.1-0.2 U/kg/day
• Adjust: 10%-15% or 2-4 U once-twice weekly to reach FBG target
• For hypoglycemia: Determine and address cause; dose by 4 U or 10-20%

If not
controlled after
FBG target is reached
2 Add 1 rapid insulin injection Change to premix insulin
(or if dose >0.5 U/kg/day), treat PPG
before largest meal twice daily Mod
excursions with mealtime insulin
(Consider initial
• Start: 4 U/day or 0.1 U/kg, or 10% basal dose. If GLP-1-RA trial) • Start: Divide current basal dose into ⅔ AM, ⅓ PM
A1C <8%, consider bolus by same amount or ½ AM, ½ PM
• Adjust: dose by 1-2 U or 10-15% once-twice • Adjust: dose by 1-2 U or 10-15% once-twice
weekly until SMBG target reached weekly until SMBG target reached
• For hypoglycemia: Determine and address cause; • For hypoglycemia: Determine and address cause;
corresponding dose by 2-4 U or 10-20% corresponding dose by 2-4 U or 10-20%

If not If not
3+ controlled, consider Add ≥2 rapid insulin injections before meals controlled, consider High
basal-bolus (“basal-bolus”) basal-bolus

• Start: 4 U/day or 0.1 U/kg, or 10% basal dose/meal. If A1C <8%, consider bolus by same amount
• Adjust: dose by 1-2 U or 10-15% once-twice weekly until SMBG target reached
• For hypoglycemia: Determine and address cause; corresponding dose by 2-4 U or 10-20%

Flexibility More Less


FBG, fasting blood glucose; GLP-1-RA, GLP-1 receptor agonist; ADA. Diabetes Care 2016; 39 (Suppl. 1): S60-S71
hypo, hypoglycemia; mod., moderate; PPG, postprandial glucose
Stepwise Insulin Titration in Type 2 Diabetes
Insulin titration according to the
guidelines
• Once initiated, basal insulin is ideally titrated from a low starting dose (usually
10 U/day) to achieve therapeutic efficacy using various titration algorithms
ADA/EASD
AACE/ACE 20152 IDF 20123
20151

10 U/day or HbA1c <8%: 0.1–0.2 U/kg Starting doses of insulin for


Initial dose per
0.1– HbA1c >8%: 0.2–0.3 U/kg safety reasons should be low
day
0.2/kg/day
increase dose Fixed regime: increase dose 2 U/day Self-titration regimen: insulin
2–4 U once or Adjustable regime: dose increases of 2 U every 3
twice weekly FBG> 180 mg/dL: increase dose by 4 U days
Titration
FBG 140–180 mg/dL: increase dose by 2 U Physician led: biweekly or
FBG 110–139 mg/dL: increase dose by 1 U more frequent contact with a
health-care professional
Target FPG,
mg/dL
- <110 <115

Target HbA1c, % <7 <7 <7

Down titration- Decrease BG <70 mg/dL: decrease dose by 10–20%


dealing with dose by 4 U BG <40 mg/dL: decrease dose by 20–40%
hypoglycemia
FPG, fasting plasma glucose; 1. Inzucchi SE, et al. Diabetes Care 2015;38:140–9;
FBG, fasting blood glucose 2. Handelsman Y, et al. Endo Pract 2015;21:1-87;
3. International Diabetes Federation. Global Guideline for Type 2 Diabetes. 2012;
Available at: http://www.idf.org/sites/default/files/IDF-Guideline-for-Type-2-Diabetes.pdf (accessed October 2015).
Simple up/down treat-to-target titration algorithms with insulin
glargine for individual dose adjustments

• Different titration algorithms based on FPG values have proven to be effective in


Studynumerous clinical studies
FPG (mmol/L) Dose titration Frequency of Down titration- dealing with
dose titration hypoglycemia

INSIGHT1 Until ≤5.5 Add 1 unit Daily Doses were reduced at the
discretion of the investigator in
response to biochemical or
clinical hypoglycaemia
LANMET2 • >10 • Add 4 units Every 3 days
• >5.5 • Add 2 units

TTT3 • ≥10 • Add 8 units Weekly Severe hypoglycaemia: decrease in


• 7.8–10 • Add 6 units insulin dose 2–4 U/day per
• 6.7–7.8 • Add 4 units adjustment
• 5.6–6.7 • Add 2 units

FPG, fasting plasma glucose; INSIGHT, Implementing New Strategies with Insulin
Glargine for Hyperglycaemia Treatment; LANMET, Insulin glargine or NPH 1.Gerstein HC, et al. Diabetes Med 2006;23:736–42;
2. Yki-Järvinen H, et al. Diabetologia 2006;49:442–51;
combined with metformin in type 2 diabetes; TTT, Treat-to-Target Trial 3. Riddle MC, et al. Diabetes Care 2003;26:3080–6.
Simple up/down titration algorithms with insulin glargine for
individual dose adjustments

• Simple dose titration manageable either by physician or


patient, leads to improved, comparable glycemic control1
• Insulin glargine offers flexible dose adjustments to meet
individual patients’ needs2,3

1. Davies M, et al. Diabetes Care 2005;28:1282–8;


2. Strange P. J Diabetes Sci Technol 2007;1:540–8;
3. Barnett A. Clin Ther 2007;29:987–99.
HbA1c goals are attained with insulin glargine using
simple titration algorithms
Mean HbA1c attained in various Treat-to-Target trials
Baseline Study end
9 8.7 8.8 8.7
8.6 8.6

8 –1.6 –1.6 –1.7 –2.0 –1.7

7.0 7.0 7.0 7.0


HbA1c%

7 6.8

5
1 2 3 4 5
Study name
Patient population
INSIGHT Observational
Study duration n=206… n=11,511…
Typically ~50% of patients attain HbA1c<7%1–5
APOLLO, Once-daily basal insulin glargine versus thrice-daily prandial insulin lispro in people with type 2 diabetes on 1. Riddle MC, et al. Diabetes Care 2003;26:3080–6;
oral hypoglycaemic agents; INITIATE, Initiate Insulin by Aggressive Titration and Education; TTT, Treat-to-Target Trial; 2. Gerstein HC, et al. Diabetes Med 2006;23:736–42;
INSIGHT, Implementing New Strategies with Insulin Glargine for Hyperglycaemia Treatment; Observational, Insulin 3. Bretzel RG, et al. Lancet 2008;371:1073–84;
glargine benefits patients with type 2 diabetes inadequately controlled on oral antidiabetic treatment. 4. Yki-Järvinen H, et al. Diabetes Care 2007;30:1364–9;
5. Schreiber SA & Haak T. Diabetes Obes Metab 2007;9:31–8.
• Results for physician-driven (weekly) versus
patient-driven (every 3 days) dose titration
AT-LANTUS Study: comparison of physician-driven versus
patient-driven titration algorithms
50
170

45
150
FBG (mg/dL)

Insulin dose (U)


40

130 35

30
110
25
*P<0.003 and †P<0.001 between algorithms at 24 weeks
90 20
0 4 8 12 16 20 24

Time since randomization (weeks)

FBG, fasting blood glucose Davies M, et al. Diabetes Care 2005;28:1282–8.


ATLAS study: Asian patients up-titrated their insulin
dose effectively when guided

Although the large majority of Asian patients have little experience with self-
titration or SMBG, Asian patients in the ATLAS study up-titrated their insulin
dose effectively when guided
• Patient-led titration resulted in a significantly higher drop in HbA1c value at 24
weeks when compared with physician-led OtraOon (−1.40% vs. −1.25%)
• Mean decrease in FBG was greatest in the paOent led group (−2.85 mmol/L vs.
−2.48 mmol/L)
• Mean daily insulin dose was higher in the patient-led group (28.9 units vs. 22.2
units)
• Incidence of severe hypoglycemia was rare in both treatment groups

ATLAS, Asian Treat to Target Lantus Study;


FBG, fasting blood glucose;
SMBG, self-monitoring of blood glucose Garg SK, et al. Endocr Pract 2015;21:143–57.
ATLAS study: HbA1c, FBG and PPG in response to
patient-led versus physician-led titration at
Week 24

Parameter Patient-led titration Physician-led titration


(n=275) (n=277)

HbA1c 7.32 [8.70 at baseline] 7.49 [8.76 at baseline]

FBG (mmol/L) 6.10 [9.00 at baseline] 6.50 [9.00 at baseline]

PPG (mmol/L) 10.30 [12.30 at baseline] 10.50 [12.30 at baseline]

ATLAS, The Asian Treat to Target Lantus Study;


FBG, fasting blood glucose;
PPG, postprandial glucose Garg SK, et al. Endocr Pract 2015;21:143–57.
ATLAS study: HbA1c levels in response to patient-led versus
physician-led titration
The study indicated patient-led insulin glargine titration is noninferior to
physician-led titration

Patient-led Physician-led
titration titration
(n=275) (n=277)
HbA1c 7.32 7.49
[8.70 at baseline] [8.76 at baseline]
-1.21% FBG 6.10 6.50
-1.25% (mmol/L) [9.00 at baseline] [9.00 at baseline]

PPG 10.30 10.50


-1.32% -1.4% (mmol/L) [12.30 at baseline] [12.30 at baseline]

For patients in group A (physician-led), titration was performed by the physician at each visit (representing common practice in
Asia); in group B (the patient-led group), patients were guided to adjust their own insulin dose twice each week

ATLAS, The Asian Treat to Target Lantus Study;


FBG, fasting blood glucose; Garg SK, et al. Endocr Pract 2015;21:143–57.
PPG, postprandial glucose
Optimized titration can lead to
effective glycemic control
Once insulin is initiated, dose titration is important1,2

Dose titration is patient-specific and should be done in order to


achieve target fasting blood glucose3

Adequate titration of the insulin dose, either by physicians or by


patients, can help patients reach treatment goals, including HbA1c <7%
and FBG <5.5 mmol/L (<100 mg/dL)2

The choice between algorithms may depend on clinical circumstances


and a patient’s willingness and ability to become more involved in
management of therapy2

1.Inzucchi SE, et al. Diabetes Care 2015;38:140–9;


FBG, fasting blood glucose; 2. Barnett A. Clin Ther 2007;29:987–99;
3. Agarwal SK, et al. J Indian Med Assoc 2013;111:626–8.
A Randomised, 52-week, treat-to-target comparing
insulin Detemir with insulin Glargine when
administered as add-on to glucose-lowering drugs in
insulin-naïve people with type 2 diabetes

Rosenstock J, et al. Diabetologia 2008;51(3):408–416

JULIO ROSENSTOCK, MELANIE DAVIES, PHILIP D. HOME,


JENS LARSEN, C KOENEN, GUNTRAM SCHERNTHANER
Study Protocol
• Aim: To compare clinical outcomes following supplementation of
OADs with basal insulin analogues detemir and Insulin Glargine
• Study design: 52-week open-label, parallel, multi-national trial comparing efficacy
and safety of insulin detemir and insulin glargine as add-on therapy to OADs in
patients with T2DM

80 sites in Europe and the United States


Population: Insulin-naïve men and women with T2DM (N=582; aged ≥18 years, BMI≤40.0
kg/m2 and HbA1c 7.5–10.0%), receiving one or two OADs (metformin, insulin secretagogues
or α-glucosidase inhibitors) for ≥4 months
Starting dose: 12 units SC QD
As per label, only detemir was used additionally in the morning if pre-dinner plasma glucose
(PDPG) >7.0 mmol/L (126 mg/dL), and only if FPG was <7.0 mmol/L or if nocturnal
hypoglycemia precluded achievement of target FPG
Glargine was given QD throughout the study as per label
Titration to a target FPG ≤6.0 mmol/L (108 mg/dL) pre-breakfast and also pre-dinner if
administered twice daily using a structured treatment algorithm
• Outcomes
– Primary: Baseline adjusted HbA1c at end of treatment

Rosenstock J, et al. Diabetologia 2008;51(3):408–416


Baseline Characteristics

Detemir (SD) Glargine (SD)


N 291 291
Age (yrs) 58.4 (10.2) 59.4 (9.6)
Wt (kg) 87.4 (16.6) 87.4 (17.4)
BMI (kg/m2) 30.6 (4.8) 30.5 (4.6)
Duration of diabetes (yrs) 9.1 (6.7) 9.1 (6.4)
A1C (%) 8.6 (0.8) 8.6 (0.8)
No significant differences between the 2 groups

Rosenstock J, et al. Diabetologia 2008;51(3):408–416


Efficacy Results
Parameter Detemir Glargine
A1C at endpoint
7.16% 7.12%
(baseline adjusted)
Insulin dose at 0.63 U/kg (0.02-3.96)
endpoint Total (QD & BID)
(median doses) 0.43 U/kg (0.02-1.98)
0.40 IU/kg
QD (45% of pts)
0.85 U/kg (0.14-3.96)
BID (55% of pts)
Completion rate 80% 87%
In-clinic FPG (mg/dl) 129.6 129.6

Rosenstock J, et al. Diabetologia 2008;51(3):408–416


Glycemic Control Achieved

60
52 52

50
Percent of patients

40 35
34

30 Detemir
Glargine
20

10

0
A1c <7% A1c <7 % w/o hypo
Rosenstock J, et al. Diabetologia 2008;51(3):408–416
Efficacy Results
To reach efficacy to a similar level to once-daily Insulin Glargine, detemir requires
higher dose (77%) and often two injections

Baseline HbA1c=8.6% in both groups


Rosenstock J, et al. Diabetologia 2008;51(3):408–416
Efficacy Results
To reach efficacy of a similar level to Insulin Glargine, detemir is given
twice daily in 55% of patients

55%
Twice-daily

45%
Once-daily

Baseline HbA1c=8.6% in both groups

Rosenstock J, et al. Diabetologia 2008;51(3):408–416 37


Efficacy Results
similar weight gain versus Insulin Glargine when used twice daily

*p<0.001; †p<0.012

Rosenstock J, et al. Diabetologia 2008;51(3):408–416


Safety Results
Event Detemir Glargine
QD-BID QD
Hypoglycemia* 5.8 6.2
Nocturnal Hypoglycemia* 1.3 1.3
Major**
Requiring assistance 9 8

At Night 5 4
Pts withdrawals due to adverse event N (%) 23 (7.9) 11 (3.85)
Injection site disorders
13 (13) 4 (5)
# of pts (# of events)

* Episodes / pt-year; **Total episodes


Rosenstock J, et al. Diabetologia 2008;51(3):408–416
Weight

Detemir Detemir Detemir Glargine Diff P


Event QD BID QD-BID QD (95% CI)
RR
Value

Weight ∆ (kg) 2.25 3.71 3.02 3.93 -0.91 - .012


(-1.62, -0.20)
Efficacy & safety of once-daily insulin Lantus
vs. twice-daily insulin detemir
Insulin glargine QD +
OADs
973 insulin naive T2D
for >1 year,
HbA1c 7%-10.5%
24 weeks
BMI < 40 kg/m2
Age 40-75 years

Insulin detemir BID + OADs

Study objective:
– non-inferiority of insulin glargine (QD) to insulin detemir (BID)
– combined end-point (HbA1c, hypos)
Trial design:
– international, multicentre, parallel, open-label, randomised
Insulin glargine QD vs. insulin detemir BID:
significantly lower insulin dose
Insulin glargine QD vs. insulin detemir BID:
significantly lower insulin dose
To achieve the same mean glycaemic control, insulin detemir patients
received 76% units (33U) more in average than insulin glargine patients

Dose of insulin
at study endpoint
Difference 33.1 IU, p<0.001

80 76.5
+ 76%
Insulin dose (U/d)

70

60

50
43.5
40

30
Insulin glargine Insulin detemir
QD BID
Detemir Dosing – T2 Diabetes Trials*

0.6 0.8

0.56 0.7 0.77


0.5
0.6
0.4 0.45

Units/kg
0.5
0.52
Units/kg

0.3 0.4

0.2
0.3 +48%
0.2
0.1
+24% 0.1

0
0 NPH BID Levemir BID
NPH QD Levemir QD

Hermansen, 2004
NN 1337, 2006

•all trials – OAD + basal insulin only


(no prandial insulin coverage)

Levemir® AMCP Dossier. Novo Nordisk 2006


Detemir in Type 2 Diabetes
Change in Mean TDD of
Basal insulin EOS FPG Weight
Study A1C insulin
(n of patients) (mg/dL) Hypo (kg)
(%) IU or U / kg
detemir QD or BID (341)a
aHaak (1) (1336)
61% used BID
-0.3 0.88 174.6 NS +1.0
(26 weeks)
Insulin only NPH QD or BID (164)
59% used BID
-0.3 0.79 172.8 NS +1.8

detemir QD or BID (195)


bRaslova (2) (1385)
69% used BID
-0.7 0.95 131 NS +0.5
(22 weeks)
Insulin only NPH QD or BID (199)
64% used BID
-0.6 0.79 132 NS +1.1

Risk
cHermansen (3) (1530) detemir BID (237)
100% used BID
-1.84 0.77 124.2 reduc +1.2
(24 weeks) tion
Insulin + OADs
NPH BID (238) -1.90 0.52 116.3 — +2.8
cRosenstock (4)
detemir QD or BID (291) +2.7
(1373) (52 weeks) 55% used BID
-1.45 0.52 & 1.006 127 NS
(+2.25 & +3.71)
Abstract only
Insulin + OADs glargine QD (291) -1.45 0.446 126 NS +3.5
cStudy 1337 (5) detemir QD (309) -0.9* 0.57 154 NS -0.4
(24 weeks)
Insulin + OADs NPH QD (158) -1.5 0.45 154 NS +0.4

*P=0.01; criteria for non-inferiority to NPH not met.


a. combination with aspart at mealtime; b. combination with aspart (det) and HSI (NPH) c. combination with 1 or 2 OADs; d. combination with
metformin only 1. Diabetes, Obesity and Metabolism 2005; 7: 56-6 2. Diabetes Research and Clinical Practice 2004; 66: 193-201 3. Diab Care
2006;29:1269-74 4. ADA 66th Annual Scientific Sessions, Washington, DC, June 2006 5. http://www.fda.gov/cder/foi/nda/2005/021-
536_Levemir_medr.PDF 6. Levemir® AMCP Dossier. Novo Nordisk 2006
Dailey et al: Insulin Glargine versus detemir meta-analysis
Study summary

Aim: To compare the baseline to endpoint weight change in


studies evaluating Insulin Glargine and/or detemir in insulin-naïve patients
with T2DM
Study design: Weighted-average, bivariate meta-analysis of 24
randomized, controlled studies. A random effects component was included
to account for potential differences between studies. Analyses were
unadjusted or adjusted for baseline covariates
and/or study covariates
Outcomes
– Primary: Changes in weight, HbA1c and weight/HbA1c
Population: 24 randomized studies of patients with T2DM, with
study duration of 4 weeks or more
Treatment received: Patients received Insulin Glargine or
detemir according to the regimen described for the
individual studies

Dailey G, et al. ADA 2009, abstract accepted


Dailey et al: Insulin Glargine versus detemir meta-analysis
Description
Of the 24 studies included in the meta-analysis, 4295 patients used once-daily
Insulin Glargine in 20 studies, while 1086 patients took detemir in four studies.
Overall, 50% of patients were taking detemir twice daily or required therapy
intensification
The change in HbA1c was comparable between Insulin Glargine and detemir
(–1.4 vs –1.4%), as was weight gain (2.3 vs 1.7 kg) and weight/HbA1c
(1.7 vs 1.2 kg/%)
By contrast, patients required a significantly higher dose of detemir versus Insulin
Glargine to achieve the same HbA1c
This analysis reveals that the weight/HbA1c ratio is similar for Insulin Glargine and
detemir, whereas patients using detemir required higher doses to achieve the same
HbA1c

Dailey G, et al. ADA 2009, abstract accepted


Dailey et al: to reach a similar HbA1c efficacy as Insulin
Glargine, detemir required a significantly higher dose

Compared with Insulin Glargine, patients using detemir required a significantly


higher dose to achieve the same HbA1c

Dailey G, et al. ADA 2009, abstract accepted


Conclusion
Uncontrolled diabetes is associated with debilitating microvascular and
macrovascular complications.

Intensive management of glycemia and other risk factors has been shown to
reduce the development and/or progression of microvascular and
macrovascular complications.

Pattern analysis is a systematic approach to identifying glycemic patterns


within SMBG data and then taking appropriate action based upon those
results.

SMBG has been shown to be an important component of diabetes


management through its ability to detect acute complications and assess
intra-day glucose excursions.

The availability of computer-based and paper-based data collection and


management tools facilitates more robust and efficient use of SMBG data,
allowing clinicians and patients to quickly identify glycemic patterns and
make more informed decisions about therapeutic adjustments that may be
required.
Conclusion
• Treating diabetes with insulin means trying to mimic normal physiology
• In comparison Glargine vs Detemir:
– Glargine: has greater biological acitivity & higher potency
– Glargine : has more patient to achieve HbA1C
– Glargine : has less dosing insulin requirement; the real once daily
– Glargine: has lower daily cost therapy for patients
– Glargine: has significant lower risk of hypoglycemia
– Glargine: has long term safety data
• Insulin glargine is the true once daily 24 hour basal insulin analogue with peakless
profile
• Once-daily injection of insulin glargine is convenient and improves patients’
compliance so they can achieve their HbA1c goals