Randomized Control Trial to Real World

Evidence of Ultra Long Acting Insulin Basal

Glargine-300:
What big clinical data teaching us ?
 Timeline for insulin developments

Eliaschewitz and Barreto Diabetol Metab Syndr (2016) 8:2

 Currently Available Basal Insulins U-100

NPH Insulin Insulin Detemir Insulin Glargine

Human; Analog; Analog;
Insulin type intermediate- long-acting long-acting
acting
Onset 2−4 hours N/A N/A
Peak 4−10 hours Relatively flat No pronounced
peak
Effective 10−16 hours Up to 24 hours Up to 24 hours
duration

U-100 /Gla 100  1 mL = 100 Unit

Niswender K, et al. Clin Diabetes. 2009;27:60-68. Courtesy of Dr. Fonseca.
Basal Insulin in Indonesia since 2017

Awitan Puncak
Jenis Insulin Lama Kerja Kemasan
(Onset) Efek

Kerja panjang (insulin analog)

Pen/vial 100
Insulin glargine (Lantus®) Hampir IU/mL
Insulin detemir
R/ Basaglaar
R/ Ezelin
U-100 1-3 jam tanpa
puncak
12-24 jam
Pen 100
U/mL

Kerja ultra-panjang (insulin analog)

Degludec (Tresiba®)* 30 -60 Hampir Sampai 48 Pen

U-300
Glargine U300 (ultra long acting basal insulin
menit

6 jam
tanpa
puncak
Tanpa
jam

> 24 jam Pen

Ultra Long Acting puncak 300U/mL

NPH: Neutral Protamine Hagedorn; Modifikasi PERKENI , Petunjuk Praktis Terapi Insulin pada pasien DM , 20115.
What’s the difference between Gla-300 and Gla-100?

Reduction of volume by 2/31

Same number
Smaller volume of
of units
injection for
Gla-300 vs Gla-100 11 Gla-100 Gla-300

Smaller surface area1,2

Gla-100 Gla-300
More compact smaller
SC depot with Gla-300
vs Gla-1001,2
1,2

For illustrative purposes only2

Different absorption kinetics:

More gradual and slower release1-4
1-4 Gla-300 has a distinct PK/PD profile vs Gla-
100:
More stable, prolonged duration
of action beyond 24 hours44

• Insulin glargine metabolism is the same regardless of Gla-100 or Gla-300 administration; M1

metabolite was confirmed as the prinicpal active moiety circulating in blood 3 5
PD, pharmacodynamic; PK, pharmacokinetic; SC, subcutaneous
1. Pettus J, et al. Diabetes Metab Res Rev. 2015 Oct 28. doi: 10.1002/dmrr.2763. [Epub ahead of print]; 2. Adapted from Sutton G et al. Expert Opin Biol Ther. 2014;14:1849-
60; 3. Steinstraesser A et al. Diabetes Obes Metab. 2014;16:873-6; 4. Becker RH et al. Diabetes Care. 2015;38:637-43
Consideration in using Insulin Therapy
from clinician perspective
 Hypoglycemia
 Weight gain
 Efficacy
 Big dosages – big volume ?

Patient :
1. Fear of injection, needle pain,
2. SMBG
 Hypoglycemia, a major limiting factor in intensive glycemic control, has a range of
consequences for patients with diabetes and an impact on the healthcare system

Tight glycemic control

↓ Complications ↑ Hypoglycemia

Each
Each 1%
1% reduction
reduction in
in HbA
HbA1c is
1c is
associated
associated with
with1
1
30
30
Glycemic
Hypoglycemia
Hypoglycemia
↑ Fear of hypoglycemia
37% control
20
20
37%
↓ Quality of life
21%
21%
↓ Productivity
POSITIVE

14%
POSITIVE

10
10
14%
Any diabetes- Myocardial Microvascula ↑ Healthcare costs

NEGATIVE
NEGATIVE
related infarction r
endpoint complication
s

Extended
Extended follow-up
follow-up for
for a
a further
further 10
10
years
years is
is associated
associated with
with2
2
30
30 ↓ Medication
20
20 24%
24%
adherence
15%
15% Insulin treatment involves
9%
10
10 9%
Any diabetes- Myocardial Microvascula
a balance
Insulinbetween glycemic
treatment involves
related
endpoint
infarction r
complication
control and between
a balance hypoglycemia
glycemic
s
control and hypoglycemia ↑ Complications
↑ Quality of life
↓ Healthcare costs

Impact on quality and cost of care

Adapted from Fidler C, et al. J Med Econ 2011;14:646-55.

Stratton IM, et al. BMJ 2000;321:405-12. 2Holman RR, et al. New Engl J Med 2008;359:1577-
1

89.

7
FOR MEDICAL and SCIENTIFIC PURPOSES ONLY – INTERNAL USE ONLY DO NOT DISTRIBUTE OR USE IN PROMOTION SAGLB.TJO.18.09.1130. Dated XXX
 Aspiration for a new basal insulin product

> 24-hour coverage Long duration of action

Reduced hypoglycaemic risk Flat time-action profile

Stable glucose lowering High day-to-day reproducibility

Flat time-action profile

Dosing flexibility Long duration of action
Long-acting analogs post-NPH ERA
basal insulin
s.c. injection
205 detemir 205
Plasma Glucose

150 150
NPH
mg/dl

glargine
95 95

Subjects with Type 1 DM

Mean±SE
4
NPH
Glucose Infusion Rate

3
INSULIN ACTION
mg/Kg/min

1
glargine
detemir
0

0 2 4 6 8 10 12 14 16 18 20 22 24

Time (hours)

Rossetti P. et al., Arch. Physiol. Biochem., 114:3-10, 2008

Profile with Gla-300 vs Gla-100 –Euglycemic Clamp PK/PD Study

3
Mean GIR (mg/min/kg)

Gla-100
2

Gla-300
1

0
0 6 12 18 24 30 36

160
Blood glucose (mg/dL)

140 Gla-100

120

100 Gla-300

0 6 12 18 24 30 36
Time, h

GIR, glucose infusion rate

Adapted from Becker RH et al. Diabetes Care. 2015;38:637-43; Bailey TS et al. Diabetes Metab.
2017 Nov 16. pii: S1262-3636(17)30538-4. doi: 10.1016/j.diabet.2017.10.001. [Epub ahead of print]

10
SAGLB.TJO.17.09.1196(2) Approved January 2018 FOR MEDICAL and SCIENTIFIC PURPOSES ONLY – INTERNAL USE ONLY
 PK/PD Insulin Glargine 300 vs Degludec

PK/PK profile

The within-day fluctuation of metabolic activity was 20% lower (p=0.047) for Toujeo than iDeg

GLA 300 provides a more stable profile than degludec with less within-day fluctuations

Bailey T, et al. (abstract) presented at 14th World Congress on Insulin Resistance, Diabetes and Cardiovascular Disease; 2016 Dec 1–3; Los Angeles,
California. Available from: http://journals.aace.com/doi/pdf/10.4158/1934-2403-23.1.1A. Date accessed: February 2017.
 Morning vs Evening injection with GLA -300

CGM Data
Euglycemic Clamp Clinical Study

Within-day Between-day
PK/PD Profile CGM data
fluctuation variability

Gla-300 presents a Low within-day Low between-day More constant 24-

more stable and fluctuation variability hour glucose
prolonged profile profile
vs. Gla-100 with Gla-300 vs.
Gla-100

Randomized,
CGM, continuous glucose monitoring; multicenter,PK,
PD, pharmacodynamic; 16-week, open-label,
pharmacokinetic; parallel-group,
T1DM, type 1 diabetes two-period crossover study in 59 patients with T1DM
Becker RHA et al. Diabetes Care 2015;38:637−643. Becker RHA et Once-daily
al. Diabetes Obes
Gla-300 or Gla-100 given in from
Metab 2015;17:261−267; Adapted the morning or evening
Bergenstal RM et al. Diabetes Care. 2017;40:554-560
 Flexibility of dosing injection time with Gla-300
• Morning vs evening injection in T1DM
– In EDITION 4, there were no clinically relevant differences in HbA1C improvement or hypoglycemia with
morning or evening Gla-300 injections1 (further confirmed by findings from the T1DM CGM trial)2

• In EDITION 1 and 2 substudies in T2DM (Months 6–9) administration of Gla-300 with a flexible dosing* time had
no effect on glycemic control and incidence of hypoglycemia 3
Pooled data of EDITION 1 and 2 substudies Pooled data of EDITION 1 and 2 substudies
(mITT population) (safety population)
60
Flexible dosing Fixed dosing
Flexible dosing

% participants experiencing
n=99 n=95 50

≥1 hypoglycemic event
Fixed dosing
HbA1C,% 40

Month 6, mean (SD) 7.30 (0.93) 7.30 (0.96) 30

Month 6–9, LS mean 0.05 (0.06) 0.00 (0.07) 20

change (SE)
10
LS mean difference 0.05
(95% CI) (–0.13 to 0.23) 0
Any time of day (24 h) Nocturnal (00:00 to 05:59 h)
Confirmed (≤70 mg/dL [≤3.9 mmol/L])
or severe hypoglycemia

*Flexible dosing time: Once-daily injection intervals of 24 ± 3 h 13

CGM, continuous glucose monitoring; CI, confidence interval; HbA1C, glycated hemoglobin A1C; LS, least squares; mITT, modified intention-to-treat; SD, standard deviation; SE, standard error;
T1DM, type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus
1. Home PD et al. Diabetes Care. 2015;38:2217-25; 2. Bergenstal RM et al. Diabetes Technol Ther 2015;17:A16–A17; 3. Adapted from Riddle M et al. Diabetes Technol Ther. 2016;18:252-7
 RCT - EDITION 1+2+3 T2DM
Patient-level meta-analysis, M12
More sustained HbA1C reduction with lower
hypoglycemia and weight gain with Gla-300 vs Gla-100 at Month 12
Participants with ≥1 confirmed (≤70 mg/dL
Mean (SE) HbA1C, % Mean (SE) HbA1C, mmol/mol [≤3.9 mmol/L]) or severe hypoglycemia event at Month 12
8.8 73
Favors Favors
8.6 Gla-300 Gla-100
8.4 ← →
68
Nocturnal 0.85 (0.77 to 0.92)
8.2 LS mean difference at (00:00 h–05:59 h)
Month 12: –0.10%
8.0
95% CI –0.18 to –0.02% 63
7.8 P=0.0174 Any time of day 0.94 (0.90 to 0.98)
7.6
(24 h)

7.4 58
0.5 1 1.5
Gla-300
7.2
Gla-100 Relative risk (95% CI)
7.0 53
Baseline W12 M6 M9 M12

• 3.2% participants on Gla-300 and 3.6% on Gla-100 had ≥1 severe hypoglycemic event at any time of day
(24 h) (relative risk 0.89; 95% CI 0.59 to 1.35)
• Less weight gain with Gla-300 vs Gla-100: LS mean difference −0.40 kg (95% CI −0.71 to −0.09;
P=0.0117)
• The mean basal insulin dose at Month 12 was 0.89 U/kg/day with Gla-300 and 0.78 U/kg/day with Gla-100,
representing
CI, confidence interval; HbA ,aglycated
1C
14%hemoglobin
higherA dose with
; LS, least
1C
Gla-300
squares; M, month; T2DM, type 2 diabetes mellitus; W, week
Adapted from Ritzel R et al. Poster presentation at ADA 2015; Abstract 1030-P
14
 Second-generation/Ultra Long Acting basal insulins show similar overall
glycemic control* – Trial-level meta-analyses – RCT

Gla-300
Gla-300 vs
vs Gla-100
Gla-100 (EDITION
(EDITION trials)
trials) IDeg
IDeg vs
vs Gla-100
Gla-100 (BEGIN
(BEGIN trials)
trials)

The difference in HbA1c reduction from baseline to 6 months between Gla-300 and Gla-100
was not statistically significant (p=0.80). The HbA1c reduction from baseline to study end
was significantly better for Gla-100 versus IDeg (p=0.024).

*Based on comparison of HbA1c, average 24 h SMPG and FPG reduction from baseline to study end between
treatments in the two separate meta-analyses. CI, confidence interval; FPG, fasting plasma glucose; IDeg, Roussel R, et al. Diabetes Metab 2018;doi: 10.1016/j.diabet.2018.02.002.
insulin degludec; LS, least squares; OD, once daily; SMPG, fasting self measured plasma glucose;

15
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Although both second-generation/Ultra Long Acting basal insulins show reduced
hypoglycemia vs first-generation Gla-100, only Gla-300 reduced both anytime and
nocturnal events – Trial-level meta-analyses – RCT

Gla-300 vs Gla-100 (EDITION trials) IDeg vs Gla-100 (BEGIN trials)

Documented
Documented symptomatic
symptomatic (≤70
(≤70 mg/dL
mg/dL [≤
[≤ 3.9
3.9 mmol/L])
mmol/L])
Documented
Documented symptomatic
symptomatic (≤70
(≤70 mg/dL
mg/dL [≤
[≤ 3.9
3.9 mmol/L])
mmol/L]) hypoglycemia
hypoglycemia hypoglycemia
hypoglycemia

Documented
symptomatic
events

Gla-300 showed a consistent lower incidence of documented symptomatic

hypoglycemia both at night and anytime (24 h) vs Gla-100. The incidence of
symptomatic hypoglycemia with IDeg vs Gla-100 was lower for nocturnal (00:01–05:59 h)
events but not for anytime (24 h) hypoglycemic events
Roussel R, et al. Diabetes Metab 2018;doi: 10.1016/j.diabet.2018.02.002.
RR, relative risk. T2D, type 2 diabetes. Data based on separate trial-level meta-
analyses. 16
FOR MEDICAL and SCIENTIFIC PURPOSES ONLY – INTERNAL USE ONLY DO NOT DISTRIBUTE OR USE IN PROMOTION SAGLB.TJO.18.09.1130. Dated XXX
Although both second-generation/UltraLong Acting basal insulins show reduced
hypoglycemia vs first-generation Gla-100, only Gla-300 reduced both anytime and
nocturnal events – Trial-level meta-analyses - RCT

Gla-300
Gla-300 vs
vs Gla-100
Gla-100 (EDITION
(EDITION trials)
trials) IDeg
IDeg vs
vs Gla-100
Gla-100 (BEGIN
(BEGIN trials)
trials)
Confirmed
Confirmed (<54
(<54 mg/dL
mg/dL [<3.0
[<3.0 mmol/L])
mmol/L]) or
or severe
severe hypoglycemia
hypoglycemia Confirmed
Confirmed (<56
(<56 mg/dL
mg/dL [<3.1
[<3.1 mmol/L])
mmol/L]) or
or severe
severe hypoglycemia
hypoglycemia

Confirmed or
severe
events

Gla-300 showed a consistent lower incidence of hypoglycemia both at night and

anytime (24 h) vs Gla-100. The incidence of hypoglycemia with IDeg vs Gla-100 was lower
for nocturnal (00:01–05:59 h) events but not for anytime (24 h) hypoglycemic events

RR, relative risk. T2D, type 2 diabetes. Data based on separate trial-level meta- Roussel R, et al. Diabetes Metab 2018;doi: 10.1016/j.diabet.2018.02.002.
analyses.
17
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The Newest and 1st of Randomized Control Trial Study
June 25th, 2018

Rosenstock JR, et al. Diabetes Care 2018

Non-inferiority of Gla-300 vs IDeg-100 in HbA1c reduction at study end

LS mean difference for Gla-300 vs IDeg-100:

-0.05 % (95 % CI -0.15 to 0.05) (−0.6 mmol/mol [−1.7 to 0.6]),
non-inferiority p-value <0.0001
Gla-300 IDeg-100
-1.6 %
9.0 75 9.0 -1.6 %
8.7

HbA1c (mmol/mol) mean ± SE

8.6
8.5 Gla-300 70 8.5
HbA1c (%) mean ± SE

IDeg-100

HbA1c (%), mean

8.0 65
8.0

60
7.5 7.5
55 7.0 7.0
7.0 7.0
50
6.5 6.5
BL W8 W12 W24 BL W24
Change from BL to W24 displayed as LS mean values
Titration period Maintenance period
Gla-300 462 448 448 430
No. of
participants: 462 447 445 425
IDeg-100
ITT population.
BL, baseline; ITT, intention-to-treat; LS, Least square; SE, standard error; W, week

Cheng et al, American Diabetes Association 2018, # OR 301

 Anytime (24 h) hypoglycemia

Incidence Event rates

Incidence, % Events per patient-year
Favors Favors RR Favors Favors
OR Gla-300 IDeg-100 p-value Gla-300 IDeg-100
Gla-300 IDeg-100 p-value Gla-300 IDeg-100 (95 % CI)
(95 % CI)
Full study period (0–24 weeks)

0.88 0.86
Confirmed (≤70 mg/dL [≤3.9 mmol/L]) 66.5 69.0 0.371 9.34 10.83 0.130
(0.66 to 1.17) (0.71 to 1.04)
0.69
0.76 0.61 0.88 0.104
Confirmed (<54 mg/dL [<3.0 mmol/L]) 14.7 18.4 0.123 (0.45 to 1.08)
(0.53 to 1.08)

Titration period (0–12 weeks)

0.74 0.77
Confirmed (≤70 mg/dL [≤3.9 mmol/L]) 47.4 54.3 0.030 8.08 10.47 0.023
(0.57 to 0.97) (0.62 to 0.96)
0.57
Confirmed (<54 mg/dL [<3.0 mmol/L]) 0.63 0.49 0.86 0.038
7.8 11.7 0.044 (0.34 to 0.97)
(0.40 to 0.99)

Maintenance period (13–24 weeks)

10.64 11.21 0.95 0.650
0.93 (0.76 to 1.19)
Confirmed (≤70 mg/dL [≤3.9 mmol/L]) 54.1 55.8 (0.72 to 1.22) 0.618
0.81
0.73 0.91 (0.48 to 1.39) 0.448
0.86
Confirmed (<54 mg/dL [<3.0 mmol/L]) 9.8 11.2 0.505
(0.56 to 1.33)

0.3 1.0 3.0 0.3 1.0 3.0

OR (95 % CI) RR (95 % CI)

Confirmed hypoglycemia included documented symptomatic or asymptomatic hypoglycemia (≤70 mg/dL or <54 mg/dL), and severe events if any; only 1 participant experienced severe hypoglycemia (1
event), in the Gla-300 group, due to a skipped evening meal and not reducing her insulin dose after a non-severe event 2 days earlier.
All p-values presented are nominal. Safety population (Gla-300, n=463; IDeg-100, n=462). CI, confidence interval; OR, odds ratio; RR, rate ratio

Cheng et al, American Diabetes Association 2018, # OR 301

 Nocturnal (00:00–06:00 h) hypoglycemia

Incidence Event Event rates

ates
Incidence, % Events per patient-year
Favors Favors RR Favors Favors
OR Gla-300 IDeg-100 p-value Gla-300 IDeg-100
Gla-300 IDeg-100 p-value Gla-300 IDeg-100 (95 % CI)
(95 % CI)
Full study period (0–24 weeks)

0.99 0.81
Confirmed (≤70 mg/dL [≤3.9 mmol/L]) 28.6 28.8 0.931 1.83 2.26 0.204
(0.74 to 1.32) (0.58 to 1.12)
1.09
1.00 0.24 0.22 0.777
Confirmed (<54 mg/dL [<3.0 mmol/L]) 6.1 6.1 0.991 (0.60 to 2.00)
(0.58 to 1.72)

Titration period (0–12 weeks)

0.77 0.65
Confirmed (≤70 mg/dL [≤3.9 mmol/L]) 15.2 18.8 0.133 1.42 2.20 0.040
(0.54 to 1.08) (0.43 to 0.98)
0.85
Confirmed (<54 mg/dL [<3.0 mmol/L]) 0.80 0.16 0.19 0.662
2.8 3.5 0.564 (0.40 to 1.79)
(0.38 to 1.69)

Maintenance period (13–24 weeks)

2.24 2.33 0.96 0.839
1.03 (0.66 to 1.40)
Confirmed (≤70 mg/dL [≤3.9 mmol/L]) 21.4 21.0 (0.74 to 1.42) 0.881
1.27
0.33 0.26 (0.57 to 2.83) 0.555
1.18
Confirmed (<54 mg/dL [<3.0 mmol/L]) 4.5 3.8 0.620
(0.61 to 2.29)

0.3 1.0 3.0 0.3 1.0 3.0

OR (95 % CI) RR (95 % CI)

Confirmed hypoglycemia included documented symptomatic or asymptomatic hypoglycemia (≤70 mg/dL or <54 mg/dL), and severe events if any; only 1 participant experienced severe hypoglycemia (1
event), in the Gla-300 group, due to a skipped evening meal and not reducing her insulin dose after a non-severe event 2 days earlier.
All p-values presented are nominal. Safety population (Gla-300, n=463; IDeg-100, n=462). CI, confidence interval; OR, odds ratio; RR, rate ratio

Cheng et al, American Diabetes Association 2018, # OR 301

 Key Messages

• Similar glycemic control with Gla-300 and IDeg-100 for HbA1c

• During the titration period (0-12 weeks), the incidence and rates
of anytime (24 h) confirmed hypoglycemia (≤70 and <54 mg/dL)
and the rate of nocturnal (00:00–06:00 h) confirmed
hypoglycemia (≤70 mg/dL) were lower with Gla-300 compare to
IDeg
• TITRATION is essential to reach METABOLIC CONTROL.
Gla-300 real world evidence (RWE) are consistent with
the results of the randomized control trial program
 Patients switching to Gla-300 had similar glycemic control and a lower RWE 2018-
DELIVER-2
incidence and rate of hypoglycemia versus other basal insulins

DELIVER
DELIVER 22 was
was aa retrospective
retrospective observational
observational analysis
analysis of
of matched
matched cohorts
cohorts (1:1
(1:1 ratio
ratio using
using aa propensity
propensity score
score based
based onon baseline
baseline demographics
demographics and and clinical
clinical
characteristics)
characteristics) of
of patients
patients with
withT2D
T2D on
on prior
prior basal
basal insulin
insulin who
who were
were switched
switched to to either
either Gla-300
Gla-300 or
or another
another basal
basal insulin*
insulin* (Gla-100,
(Gla-100, insulin
insulin detemir
detemir or
or
degludec).
degludec). Data
Data was
was obtained
obtained from
from US
US Predictive
Predictive Health
Health Intelligence
Intelligence Environment
Environment EMR EMR database
database (March
(March 2015
2015 to
to March
March 2016)
2016) (n=1,819
(n=1,819 per
per cohort)
cohort)

Comparable HbA1c reductions Lower hypoglycemia incidence Lower hypoglycemia event rate
at 6 months at 6 months† at 6 months†

21% 19%
difference difference
HbA1c (%)

p=0.015 p=0.041
Δ=-0.51% Δ=-0.51%
p<0.001 p<0.001
% of patients with hypoglycemia 20% Gla-300 (n=1,819) 0.8
9.5 Gla-300 (n=1,819)

Adjusted event rate (PPPY)

0.79
18.1% 0.7
8.95% 15% 42%
8.5 8.93%
15.4% difference
0.6 0.64
8.43% 8.43% 0.5 32% difference
p=0.001
7.5 10% 0.4 p=0.041

0.3
7.0% 0.31
6.5 5% 0.2
0.21
4.0% 0.1
5.5 0% 0
All hypoglycemia Severe hypoglyc... All hypoglycemia Severe hypoglyc...
Prior insulin to Prior insulin to
Gla-300 other basal insulin
(n=1,819) (n=1,819)
Difference between Gla-300 vs other basal insulin p=0.928

EMR, electronic medical record; PPPY, per-patient-per year; T2D, type 2 diabetes.
*Predominantly a first-generation basal insulin. †Adjusted for baseline hypoglycemia. Severe
hypoglycemia was defined as inpatient/emergency department (ED) related hypoglycemia

Zhou LF, et al. Diabetes Obes Metab 2018;20:1293–97.

24
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OR USE IN PROMOTION SAGLB.TJO.18.09.1130. Dated XXX
 RWE-
Patients switching to Gla-300 had a lower risk of hypoglycemia-related DELIVER-2
2018
hospitalization, ED services and outpatient visits versus other basal insulins

DELIVER
DELIVER 22 was
was aa retrospective
retrospective observational
observational analysis
analysis ofof matched
matched cohorts
cohorts (1:1
(1:1 ratio
ratio using
using aa propensity
propensity score
score based
based on
on baseline
baseline demographics
demographics and
and clinical
clinical
characteristics)
characteristics) of patients with T2D on prior basal insulin who were switched to either Gla-300 or another basal insulin* (Gla-100, insulin detemir or
of patients with T2D on prior basal insulin who were switched to either Gla-300 or another basal insulin* (Gla-100, insulin detemir or IDeg).
IDeg).
Data
Data was
was obtained
obtained from
from US
US Predictive
Predictive Health
Health Intelligence
Intelligence Environment
Environment EMR EMR database
database (March
(March 2015
2015 to
to March
March 2016)
2016) (n=1,819
(n=1,819 per
per cohort)
cohort)

Incidence of hypoglycemia-related HCRU Event rate of hypoglycemia-related HCRU NS

20 1.4 p=0.160
18 p=0.011 1.22
Patients with hypoglycemia-

1.2

Adjusted mean event rate of

Switched to Gla-300

hypoglycemia-related visits
16 15.4
Switched to other basal insulin
related visits (%)

14 1.0
1.03

(events/PPY)
12
12.6 0.8
10
8 p=0.007 0.6
p=0.037
6 4.3 5.1 0.4
NS
p=0.304 p=0.012
0.22
4
0.2 0.14 0.2 0.13
2 2.8 3.1
0 0.0
Hospitalization Emergency Outpatient Hospitalization Emergency Outpatient
department department

Considering all hypoglycemia-related HCRU including hospitalizations, ED and outpatient visits,

switching to Gla-300 resulted in overall savings of US$1,439 per patient per year

Predominantly first-generation basal insulins ED, emergency department; EMR, electronic medical records; HCRU,
healthcare resource utilization; IDeg, insulin degludec; NS, non significant; T2D, type 2 diabetes.

Zhou LF, et al. Diabetes Obes Metab 2018;20:1293-97.

25
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OR USE IN PROMOTION SAGLB.TJO.18.09.1130. Dated XXX
Patients switching to Gla-300 had similar glycemic control and similar rate (vs second
generation IDeg) or lower rate (vs first generation Gla-100/IDet) of severe hypoglycemia

RWE 2018 -
LIGHTNING PSM

LIGHTNING
LIGHTNING was was aa retrospective
retrospective observational
observational electronic
electronic medical
medical record
record study
study (Humedica
(Humedica database)
database) of
of patients
patients with
with T2D
T2D who
who switched
switched
to
to Gla-100,
Gla-100, detemir,
detemir, degludec
degludec (IDeg)
(IDeg) or
or Gla-300.
Gla-300. This
This analysis
analysis reports
reports results
results from
from patients
patients switching
switching between
between basal
basal insulin
insulin treatments
treatments
(April
(April 2015
2015 to
to Dec
Dec 2016)
2016)

Comparable HbA1c reductions following a switch to Gla- Rates of severe hypoglycemia following a switch to
300 or comparator basal insulin Gla-300 or comparator basal insulin
PSM-matched
25
Gla-300 Gla-100 Gla-300 IDet Gla-300 IDeg
cohorts n=734 n=720 n=735 n=706 n=181 n=246
0

(event/100 patient-years)
20 p=0.002
Mean (SE) HbA1c reduction (%)

15.1

Mean event rate

-0.2
15 p=0.009

-0.4 9.7
10 NS
p=0.370
-0.50
-0.6 -0.56 (2.0) 5.3
-0.59 -0.59
(1.9)
(1.9)
(1.9) 5 3.6 3.6 3.4
-0.8
NS NS -0.80
p=0.789 p=0.382 (1.8)
-0.89
0
-1 (1.9) PSM-matched Gla-300 Gla-100 Gla-300 IDet Gla-300 IDeg
cohorts n=2,615 n=2,717 n=2,602 n=2,647 n=1,517 n=1,458
NS
p=0.591
HbA1c reduction: 0.59% vs 0.56% 0.59% vs 0.50% 0.80% vs 0.89%

Hypoglycemic events were partly captured through use of natural language processing.
Severe hypoglycemia was defined as any hypoglycemic event (identified by ICD 9/10 codes
or plasma glucose level ≤70 mg/dL) related to an emergency department encounter. IDeg,
insulin degludec; IDet, insulin detemir; NS, non significant; PSM, propensity score matching;
T2D, type 2 diabetes.

Meneghini L, et al. Diabetes Technol Therap 2018;20(Suppl 1):A45-46.

26
FOR MEDICAL and SCIENTIFIC PURPOSES ONLY – INTERNAL USE ONLY FOR INTERNAL USE ONLY – DO NOT DISTRIBUTE
DO NOT OR USE
DISTRIBUTE IN PROMOTION
OR USE IN PROMOTION SAGLB.TJO.18.09.1130. Dated XXX
 Conclusion
• GLA 300 as an Ultra Long Acting Basal Insulin has complete clinical
studies program from PK/PD, RCT and Real World Evidence.

• GLA 300 is an Ultra Long Acting Basal Insulin which mimicking

insulin secretion endogen provide profile PK/PD as follow :
• less fluctuating steady-state PD profiles (lower within-day variability) and more
evenly distributed PK profiles
• lower within-day and day-to-day variability in glucose lowering effect compare to
IDeg

• Offer flexibility dosing injection +/- 3 hours

• RCT - BRIGHT Study confirmed more Hypo benefit of GLA 300 vs IDeg
during TITRATION PERIOD. TITRATION is essential to
Metabolic Control

• RWE study showed switching from other basal insulin to GLA 300 will
result :
– Effective in lowering HbA1C
– Hypo benefit both Nocturnal and anytime of the day
– Cost effective