Breaking the Complexities of

T2DM Management with SOLID

evidence of
iGlarLixi

MAT-IN-2400980-V1.0/07/2024

This event is only for invited and Registered Endocrinologist or specialist in Internal Medicine only.
India and Type 2 Diabetes

LANDMARC is the first large-scale, longitudinal, prospective, observational real-world study to

investigate management & complications in type 2 diabetes across India over a period of 3 years

01 02
63%
03
66% 04
21%
The underlying
pathophysiology of type 2
T2DM patients are Patients have micro
diabetes is complex, with Participants are obese
uncontrolled (18%) and macro
(HbA1c>7%) (Mean BMI 27.2kg/m2) (3.3%) vascular
multiple contributing
abnormalities. complications

Sun H et al. Diabetes research and clinical practice. 2022 Jan 1;183:109119; Das AK et al. Endocrinology, Diabetes & Metabolism. 2023 Sep;6(5):e422..
Advancing insulin therapy in clinical practice

Options for advancing basal insulin therapy in adults with insufficiently controlled T2D include:

Basal insulin Basal + bolus/ Basal insulin + Combination injectable

Premixed insulin a GLP-1 RA of basal insulin
and GLP-1 RA

FRC, fixed-ratio combination; GLP-1 RA, glucagon-like peptide-1 receptor agonist; T2D, Type 2 diabetes. Davies MJ, et al. Diabetes Care 2018;61:2461–98.
Unmet needs with complex regimens in T2D management

Despite evolution of many glucose-lowering therapies, glycemic control remains suboptimal

for many people with diabetes

Factors impacting the potential

Complex insulin regimens are
treatment burden of complex
associated with:
treatment regimens:

Multiple Risk of hypoglycemia Lifestyle Multiple

injections and weight gain adjustments daily injections

Reduced
flexibility Diet Physical activity

Meece J. Diabetes Ther 2018;9:877–90; Rizvi A and Ligthelm R. Insulin 2007;2:68–79.

Combining
Basal insulin+GLP-1 RA
Combination Injectable

Two titratable drugs, basal insulin and GLP-1 RA combined in a single injection is called as
01
combination injectable or a fixed-ratio combination.

Once-daily combination injectable containing basal insulin + GLP-1 RA :

02  Insulin glargine U100 + lixisenatide (iGlarLixi)

Diabetes Care Volume 46, Supplement 1, January Soliqua® SoloStar® PI.pdf (sanofi.in) Accessed on 26Feb2024
2023
What opportunities could a combination injectable of basal insulin
and GLP-1 RA provide for patients?

Opportunity to Earlier achievement Potential to delay

address multiple and greater underlying disease
physiologic defects persistence of glycemic progression and
using combinations of and other therapeutic disease-related vascular
various antidiabetic drugs goals complications
with complementary
mechanisms of action

Increased convenience, Potential reduction

therefore improved in risk of side effects
adherence to therapy with combined drugs at
lower doses vs up-titration
of single doses

1. Levin PA. Diabetes Metab Syndr Obes 2016;9:355−69; 2. Liakopoulou P, et al. Endocrine 2017;56:485−94; 3. Owens DR, et al. Diabetes Obes Metab 2017;19:1339–52.
Combination of insulin with GLP-1 RA utilize a complementary
approach to help achieve glycemic control

Basal Insulin 1,2

GLP-1 RA3,4

Targets hepatic glucose

Glucose-dependent insulin
over-production by
release:
decreasing gluconeogenesis:

↓ Glucagon
secretion,
delayed gastric emptying,
↓ Fasting blood glucose
↓ Post-prandial glucose
excursions

Result: Result:

Improve post-prandial blood

Reduce fasting blood glucose
glucose control

1. Balena R, et al. Diab Obes Metab 2013;15:485–502; 2. Wang Z, et al. Diabetes Care 2010;33:1555–60; 3. Baggio LL and Drucker DJ. Gastroenterol 2007;132:2131–57;
4. Holst JJ, et al. Physiol Rev 2007;87:1409–39; 5. Blonde L, et al. Curr Med Res Opin 2019;35:793–804.
Combination injectable iGlarLixi targets 7 out of 8 pathophysiologic
abnormalities of T2DM

↑ Glucose dependent
↓ Hepatic glucose production
insulin release
↓ Gluconeogenesis
Liver β-cells

↓ Glucose dependent
glucagon release
Muscle α-cells
↑ Glucose uptake in muscles
Hyperglycemia

↑ Satiety
Fat Brain

↓ Lipolysis

Kidney Intestine

↓ Gastric emptying

DeFronzo RA et al. Diabetes. 2009 Apr 1;58(4):773-95. Soliqua® SoloStar® PI.pdf (sanofi.in) Accessed on 26Feb2024
 Complementary modes of action of basal insulin glargine U100 +
prandial GLP-1 RA lixisenatide provide a rationale for combination

Effective HbA1c reduction

Improved GI
tolerability vs
monocomponents More people achieving
glycemic targets

Insulin
Glargine U100
+ Lixisenatide
complementary
No additional risk of hypoglycemia/ approach to
Lower rates of hypoglycemia HbA1c control Address multiple
(vs intensified insulin regimes) pathophysiological defects

Weight benefits / neutrality FPG + PP

(vs intensified insulin regimes) glucose control

Complementary mechanisms of action of insulin glargine and lixisenatide in a single daily injection

GLP-1 RA, glucagon-like peptide 1 receptor agonists; GI, gastrointestinal.

1. Perreault L, et al. Adv Ther2019;36:265-77; 2. Blonde L, et al. CurrMed Res Opin2019;35:793–804; 3. Davies MJ, et al. Diabetes Care 2022;45:2753–86; 4. Gough S, et al. Lancet Diab Endocrinol
2014;2:885–9; 5. Buse JB, et al. Diabetes Care 2014;37:2926–33; 6. Rosenstock J, et al. Diabetes Care 2016;39:2026–35; 7. ArodaVR, et al. Diabetes Care 2016;39:1972–80.
Guideline
recommendations
 Global Guideline Recommendations on Combination
Injectable

ADA 2024 AACE/ACE 2023 ADA/EASD 2022

• The combination of basal • Failure of OADs or • The combination of basal

insulin and GLP-1 RA* has GLP-1 RA: insulin with GLP-1 RA
potent glucose-lowering If glycemic targets are not results in greater
actions and less weight achieved with these glycaemic lowering
gain and hypoglycemia therapies, basal insulin efficacy than the mono-
compared with intensified should be added alone or components, with less
insulin plans. as a basal insulin/GLP-1 weight gain and lower
RA combination injection. rates of hypoglycemia
than with intensified insulin
• Although premixed insulin regimens, and better
requires fewer injections, it gastrointestinal
also has less flexibility for tolerability than with GLP-
dosing adjustments and may 1 RA alone.
increase hypoglycemia

*administered via separate injections of individual products or single injection of a fixed-ratio product

Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2024. Endocrine Practice. 2023 May 4. Diabetes care. 2022 Nov 1;45(11):2753-86.
" Diabetes Care 47, no. Supplement_1 (2024): S158-S178.
iGlarLixi
clinical evidence
 iGlarLixi Evidence in Adults with T2DM

Phase IIIb trails:

• iGlarLixi vs IDegAsp in T2DM sub-optimally controlled on OADs

• iGlarLixi vs BIAsp30 in T2DM sub-optimally controlled on basal insulin

Phase III trials:

• iGlarLixi in T2DM sub-optimally controlled on OAD
• iGlarLixi in T2DM sub-optimally controlled on basal insulin
• iGlarLixi in T2DM sub-optimally controlled on GLP-1RA

RWE studies:
• iGlarLixi vs basal-plus rapid acting insulin
• iGlarLixi vs basal-bolus
• iGlarLixi in Ramadan

Systematic review & Meta Analysis:

• iGlarLixi vs IDegLira

Liu M et al. Diabetes Obes Metab. 2024;1‐10. doi:10.1111/dom.15724; Rosenstock J et al. Diabetes Care. 2021 Oct 1;44(10):2361-70. ; Rosenstock J, et al. Diabetes Care 2016;39:2026−35 Aroda VR, et al. Diabetes Care 2016;39:1972–80 ; Blonde L, et al. Diabetes Care 2019;42:2108–2116
SoliSimplify: McCrimmon RC, et al. Data presented at ADA 2022; 260-OR. Tabák ÁG et al. Diabetes Ther. 2020;11:305–18. ; BEYOND: Giugliano D et al. Diabetes Care 2021;44:1353–60. Cai X et al. Expert opinion on pharmacotherapy. 2017 Nov 22;18(17):1789-98.; Home PD et al. Diabetes, Obesity and Metabolism.
2020 Nov;22(11):2170-8.; Visolyi GÁ et al. Canadian Journal of Diabetes. 2023 Mar 22; Jammah AA et al. Primary Care Diabetes. 2021 Feb 1;15(1):132-7.
Phase III/IIIb evidence:
iGlarLixi in T2DM sub-optimally controlled
on OADs
• iGlarLixi vs IDegAsp
• iGlarLixi vs individual mono-components

iGlarLixi in T2DM sub-optimally controlled on

basal insulin
• iGlarLixi vs BIAsp30
• iGlarLixi vs iGlar
iGlarLixi in T2DM sub-optimally controlled on
GLP-1 RA
• Durability over 52 weeks
iGlarLixi vs IDegAsp efficacy and safety in T2DM sub-optimally
controlled on OADs: Soli-D randomized controlled trial

Study Objective: 24-week, open-label, phase 3 study to compare the efficacy and safety of iGlarLixi with
IDegAsp in Chinese adults with sub-optimally controlled T2DM on OADs (n=582)

Population
Follow-up
iGlarLixi once daily (n=291) Primary
• Adult T2DM with ≥3 months on Screening (3 days)
Endpoint
stable dose of metformin ± a second
OAD (SU, glinide, alpha GI, DPP4i or Metformin ± SGLT2i
SGLT2i)
Follow-up Non-inferiority
• BMI <40 kg/m² IDegAsp once daily (n=291)
(3 days) in HbA1c
• HbA1c change from
Open-label randomized treatment period
• ≥7.5 to ≤11% if previously on baseline to
(24 weeks)
metformin ± SGLT2i week 24
• ≥7.0 to ≤10% if previously on Randomization End of treatment
metformin + second non-SGLT2i 1:1 (Week 24)
OAD
Treatments titrated to a fasting SMPG target of 80-100 mg/dL

iGlarLixi 1:1 and 2:1 pens were used. iGlarLixi was self-administered once-daily within 1 hour before the first meal
IDegAsp was self-administered once-daily before the largest meal of the day
Recommended starting daily dose was 5 dose steps for iGlarLixi and 5 U for IDegAsp.
DPP-4I, dipeptidyl peptidase 4 inhibitors; alpha GI, alpha-glucosidase inhibitor; HbA1c, glycosylated haemoglobin; N, number of participants; OAD, oral antidiabetic drugs; SGLT2I, sodium-glucose cotransporter-2
inhibitors; SMPG, self-monitored plasma glucose; SU, sulphonyl urea; T2DM, type 2 diabetes, IDegAsp Insulin degludec 70% /insulin aspart (30%) Liu M et al. Diabetes Obes Metab. 2024;1‐10.
doi:10.1111/dom.15724
iGlarLixi vs IDegAsp in T2DM sub-optimally controlled on OADs:
Soli-D study Endpoints

Key secondary Other secondary Safety endpoints

efficacy endpoints efficacy endpoints

• Superiority in change in HbA1c • Change in FPG from • Incidence and event rates of
from baseline to Week 24 baseline to Week 24 hypoglycaemia:

• Superiority in change in body • Change in 7-point SMPG • Any hypoglycaemic event

weight from baseline to Week 24 profile from baseline to • ADA Level 1 (<70 mg/dL
Week 24 and ≥54 mg/dL)
• Proportion of participants to reach
HbA1c<7% at Week 24 • Proportion of participants • ADA Level 2 (<54 mg/dL)
• Proportion of participants reaching reaching HbA1c target
<7% at Week 24 with no • ADA Level 3 (severe
HbA1c targets <7% without body hypoglycaemia†)
weight gain at Week 24 hypoglycaemia¥

• Total insulin dose in each • AEs, serious AEs,

• Proportion of participants reaching
group at Week 24 AEs of special interest
HbA1c <7% with no body weight
gain at Week 24 and no
hypoglycaemia¥

¥
defined as ADA Level 1, 2 or 3
ADA Level 1 hypoglycaemia: blood glucose concentration < 70 mg/dL but ≥ 54 mg/dL; ADA Level 2 hypoglycaemia: blood glucose concentration < 54 mg/dL; †Level 3
hypoglycaemia: a severe event characterized by altered mental and/or physical functioning that requires assistance from another person for recovery. Liu M et al. Diabetes Obes Metab. 2024;1‐10.
doi:10.1111/dom.15724
iGlarLixi vs IDegAsp in T2DM sub-optimally controlled on OADs:
Soli-D study Baseline characteristics were similar

Metformin ±
Duration of
Age, years Female, n (%) BMI, kg/m2 HbA1c, % SGLT2i use at
T2DM, years screening, n (%)

iGlarLixi
56.3 ± 10.2 141 (48.5) 25.92 ± 3.47 8.56 ± 5.68 8.58 ± 0.93 151 (51.9)
(N=291)

IDegAsp
(N=291) 57.5 ± 9.9 136 (46.7) 25.42 ± 3.25 9.06 ± 6.00 8.53 ± 0.90 151 (51.9)

Data presented as mean ± SD unless specified otherwise.

BMI, body mass index; SD, standard deviation
Liu M et al. Diabetes Obes Metab. 2024;1‐10.
doi:10.1111/dom.15724
iGlarLixi showed non-inferiority and superiority over IDegAsp in
HbA1c reduction: Soli-D study

Change in HbA1c from baseline to week 24

iGlarLixi IDegAsp
Mean ± SD HbA1c, % (n = 291) (n = 291)
Mean ± SE change in HbA1c from baseline

9.5 Baseline 8.58 ± 0.93 8.53 ± 0.90

iGlarLixi

• The LS
9 mean difference between iGlarLixi IDeg Asp

versus IDegAsp was −0.20 (95% CI: −1.88 ± 0.05 −1.68 ± 0.05

from baseline to Week 24, (%)

−0.33;
8.5 −0.07) -1

LS mean ± change in HbA1c

to Week 24, (%)

• Non-inferiority
8 of iGlarLixi over IDegAsp -1.2
on HbA1c (%) change from baseline to
Week
7.5 24 was demonstrated (p<0.001) -1.4
6.83
± 0.74
• The superiority
7 of iGlarLixi versus -1.6
6.58
6.83 ± 0.74
IDegAsp in terms of HbA1c reduction was ± 0.71
6.58 ± 0.71 -1.8
also6.5shown (superiority p-value 0.003)
-2
6
Baseline Week 4 Week 8 Week 12 Week 18 Week 24 LS Mean difference: −0.2%
-2.2
Visit (95% CI −0.33, −0.07) P<0.001 non-inferiority
Number of participants

291 277 268 276 276

(97.5% CI −0.35, −0.05) P=0.003 superiority
iGlarLixi 274

IDegAsp 291 275 276 280 282 285

LS, least square; SD, standard deviation; SE, standard error.

Liu M et al. Diabetes Obes Metab. 2024;1‐10.

doi:10.1111/dom.15724
iGlarLixi demonstrate body weight benefit versus IDegAsp: Soli-D study

Change in body weight from baseline to week 24 Key secondary endpoints

OR (97.5% CI)
1.89 (1.25, 2.85)
Mean ± SD body iGlarLixi IDegAsp
weight, kg (n = 291) (n = 291) 72.5
HbA1c <7% at week 24 Hb A1 c < 7 % a t we e k 2 4

p<0.001
Baseline 70.7 ± 13.36 69 ± 12.53 59.8

LS Mean difference: -1.49

OR (95% CI)
LS Mean change in body weight ± SE, kg

(97.5% CI -2.32, −0.66)

2 2.59 (1.79, 3.76)
P<0.001 superiority
40.5
HbA1c <7% without body
p<0.001
1.5
Hb A1 c < 7 % wi th o u t b o d y we ig h t g a in a t we e k 2 4

weight gain at week 24

21.3

1 1.2 + 0.25

OR (95% CI)
0.5 2.34 (1.52, 3.6)
HbA1c <7% without body 26.5
weight gain at week 24 and p<0.001
0
Hb A1 c < 7 % wi th o u t b o d y we ig h t g a in a t we e k 2 4 a n d n o h y p o g ly c a e m i a *

no hypoglycaemia* during
Series1 13.4
treatment .
-0.5
-0.3 + 0.29 0 10 20 30 40 50 60 70 80
-1 Proportion of participants (%)
iGlarLixi (n=291) IDegAsp (n=291)

Greater proportion of participants treated with iGlarLixi reached HbA1c <7%, HbA1c <7% without body
weight gain and HbA1c <7% without body weight gain and no hypoglycaemia versus IDegAsp
*Defined as ADA Level 1, 2 or 3 hypoglycaemia
ADA, American Diabetes Association; CI, confidence interval; OR, odds ratio. Liu M et al. Diabetes Obes Metab. 2024;1‐10.
doi:10.1111/dom.15724
 iGlarLixi showed reduction in 7-point SMPG values: Soli-D
study
Change in 7-point SMPG from baseline to week 24 Change in PPG from baseline to week 24

Favors IDegAsp
16
iGlarLixi at baseline IDegAsp at baseline
15
iGlarLixi at week 24 IDegAsp at week 24 Mean of all
14 Breakfast Lunch Dinner meals
Mean (±SE) mmol/L

13 1.0
1.26
12 0.5 (95% Cl -7.2, 9.54)

LS mean difference in PPG

11 0.0

reduction, mg/dL
10

Favors iGlarLixi
-0.5
9
-1.0
8 -18.18 -14.22
-1.5 (95% Cl -26.1, -10.26) (95% Cl -20.7, -7.56)
7
6 -2.0 -25.92
(95% Cl -34.74, -17.28)
5
Before 2-hr after Before 2-hr after Before 2-hr after Bedtime
breakfast breakfast Lunch Lunch Dinner dinner

LS mean difference¥ in 7-point SMPG between iGlarLixi vs IDegAsp was -7.93 mg/dL

¥LS mean difference in 7-point SMPG between iGlarLixi vs IDegAsp: 95% CI: -0.75, -0.14
Mean 7-point SMPG reductions: iGlarLixi -61.2 mg/dL (2.16) and IDegAsp -52.2 mg/dL (1.98)]
Values in mg/dL here are calculated from the values in mmol/L given in the publication using the formula: mg/dL = 18 × mmol/L. Liu M et al. Diabetes Obes Metab. 2024;1‐10.
doi:10.1111/dom.15724
Lower mean total insulin dose required for iGlarLixi: Soli-D study

Mean insulin dose at week 24

60

LS mean difference -6.10 ± 1.18 U/day

50 (95% CI -8.42, -3.78)

40
34.1
30 28.2
(0.48 U/Kg)
(0.40 U/Kg)
20

10

0
iGlarLixi IDegAsp

Final mean Lixi dose was 16.2 μg

LS mean difference in U/kg: -0.08 U/Kg (95% CI -0.11, -0.05)
Liu M et al. Diabetes Obes Metab. 2024;1‐10.
doi:10.1111/dom.15724
Lower incidence and event rate of hypoglycaemia, including nocturnal
hypoglycaemia with iGlarLixi compared with IDegAsp: Soli-D study
iGlarLixi (Safety population; n=290) IDegAsp (Safety population, n=291)

Event rate of
Incidence of Hypoglycemia, %
Hypoglycemia, rate PPY
Any Hypoglycemia ADA Level 1 ADA Level 2 Any Hypoglycemia
Hypoglycemia Hypoglycemia
50 RR (95% CI)
OR (95% CI) OR (95% CI) OR (95% CI)
48 0.79 (0.56-1.11) 0.75 (0.53-1.06) 50 0.79 (0.43-1.45) 0.71 (0.52-0.98)
50
46 45

44 40
45
42 35
40.5
40
39.5 30 -29%
40
25
38
35 33.1 20
36 35.2
15
34
30 8.6 2.72
10 6.9 1.9
32
5
30 25
iGlarLixi IDegAsp iGlarLixi IDegAsp 0
iGlarLixi IDegAsp iGlarLixi IDegAsp

The incidence of nocturnal hypoglycaemia^ (between bedtime and waking) was lower with
iGlarLixi (2.8%) versus IDegAsp (5.8%) (OR: 0.46, 95% CI: 0.19, 1.08)

^ADA Level 1, 2 or 3; There were no reports of ADA Level 3 hypoglycaemia across both groups.
OR and CI are based on logistic regression model adjusting for treatment group, randomization strata of HbA1c and previous OADs.
ADA Level 1 hypoglycaemia: blood glucose concentration < 70 mg/dL but ≥ 54 mg/dL; ADA Level 2 hypoglycaemia: blood glucose concentration < 54 mg/dL; Level 3
hypoglycaemia: a severe event characterized by altered mental and/or physical functioning that requires assistance from another person for recovery. PPY, per patient year Liu M et al. Diabetes Obes Metab. 2024;1‐10.
doi:10.1111/dom.15724
Summary & Conclusion: Soli-D study

In Soli-D, a 24-weeks, head-to-head study conducted in Chinese T2DM patients sub-optimally

controlled on OADs, iGlarLixi has demonstrated versus IDegAsp:

Non-inferiority Superior body More patients Lower risk of No unexpected

and statistical weight benefit achieve hypoglycaemic safety findings
superiority in composite events
HbA1c endpoints
reduction

iGlarLixi should be considered as a valuable option for advancing therapy in people with
T2DM, suboptimally controlled on OADs.

Liu M et al. Diabetes Obes Metab. 2024;1‐10.

doi:10.1111/dom.15724
Phase III/IIIb evidence:
iGlarLixi in T2DM sub-optimally controlled
on OADs
• iGlarLixi vs IDegAsp
• iGlarLixi vs individual mono-components

iGlarLixi in T2DM sub-optimally controlled on

basal insulin
• iGlarLixi vs BIAsp30
• iGlarLixi vs iGlar
iGlarLixi in T2DM sub-optimally controlled on
GLP-1 RA
• Durability over 52 weeks
iGlarLixi vs iGlar vs Lixisenatide in OAD Uncontrolled Patients:
LixiLan-O study
Study Objective: Randomized, open-label, parallel-group phase III study to assess
superiority of iGlarLixi over lixisenatide and non-inferiority of iGlarLixi over iGlar in
HbA1c change from baseline to Week 30 (n = 1170)

Lixisenatide + metformin
20 µg
People with T2D 10 µg n=234
iGlarLixi + metformin
(1:2:2)
• Receiving metformin ± additional OAD n=469
R
Run-in phase 4
• HbA1c 7%–9% if receiving two OADs weeks iGlar + metformin
(OADs except
• HbA1c 7.5%–10% if receiving metformin metformin
n=467
discontinued)
alone
30 weeks

iGlarLixi was self administered 0-60 minutes before breakfast

U, units, OD, once daily; QW, once weekly, BD, twice daily, ER, extended release
Rosenstock J, et al. Diabetes Care 2016;39:2026−35
 iGlarLixi demonstrated superior HbA1c reduction and significant
reduction in average 7-point SMPG (LixiLan-O study)
HbA1c reduction Average 7-point SMPG profile

Baseline 8.1±0.7 8.1±0.7 8.1±0.7

0.0
-0.2 Series1
LS mean change (%)

-0.4
-0.6
-0.8 –0.9
-1.0
-1.2
–1.3
-1.4
-1.6 –1.6 iGlarLixi iGlar
iGlarLixi (n=468)
iGlar (n=466)
-1.8 p<0.0001 Lixisenatide
Lixisenatide (n=233)
p<0.0001

FPG change 2-hour PPG reduction

Baseline 178.0 175.7 176.4 Baseline 275.1 262.8 264.6
0.0 0.0
Series1
Randomized, open-label, parallel-group Series1
-10.0 -20.0
30-week treatment trial
LS mean change (mg/dL)

LS mean change (mg/dL)

-20.0 -27
-40.0
-30.0
-59.6
-40.0 -60.0
-50.0 -80.0 -82.6
-59.4
-60.0 -63 -102.4
-100.0 –42.9
-70.0 –3.6 95% CI: –50.3, –35.4
95% CI: –7.2, –0.7
–36.0 –19.8
95% CI: –39.6, –30.6 95% CI: –29.3, –10.3

Final mean basal insulin daily dose: iGlarLixi (39.86 ± 14.9U) iGlar (40.3 ± 6 14.9U)
Values in mg/dL here are calculated from the values in mmol/L given in the publication using the formula: mg/dL = 18 × mmol/L Rosenstock J, et al. Diabetes Care 2016;39:2026−35
 In the iGlarLixi group, 74% of patients achieved HbA1c target
<7% (LixiLan-O study)

Individuals at target HbA1c Weight change Hypoglycemia$

Baseline 89.4 89.8 90.8
Individuals with events No. of events per
100.0
Proportion of individuals (%)

2.0 (%) patient year

40.6*

LS mean change (kg)

50.0 5.0
80.0 14.3* 1.0
36.4* 1.1
74 40.0 4.0
60.0 16.4*
0.0
59 56 Series1
–0.3 30.0 3.0
40.0 -1.0
40
33 20.0 2.0
20.0 25.6
-2.0 –2.3 23.6
19 –1.4* 10.0 6.4 1.0
0.0 95% CI: –1.9, –0.9 0.3
-3.0 1.4
HbA1c <7% HbA1c ≤6.5% –2.0 0.0 0.0
1.2

95% CI: 1.4, 2.6 n=469 Series1

n=467 n=233 n=469 Series1
n=467 n=233

iGlarLixi (n=468) iGlar (n=466) Lixisenatide (n=233)

§One event of severe hypoglycemia was reported during the study and occurred in the iGlar group Frias J et al. Diabetes, Obesity and Metabolism. 2018 Sep;20(9):2314-8.; Rosenstock J, et al. Diabetes Care 2016;39:2026−35
iGlarLixi showed low gastrointestinal adverse effects compared with
Lixisenatide alone and the side effects subsided over time (LixiLan-O study)

GI TEAEs from LixiLan-O study

Individuals, % (n), with at least one…

GI TEAEs iGlarLixi Lixisenatide iGlar
(n=469) (n=233) (n=467)

Nausea 9.6 (45) 24.0 (56) 3.6 (17)

 discontinuation 0.4 (2) 2.6 (6) 0

Vomiting 3.2 (15) 6.4 (15) 1.5 (7)

 discontinuation 0.4 (2) 1.7 (4) 0
Randomized, open-label, parallel-group 30-week
treatment trial

Diarrhea 9.0 (42) 9.0 (21) 4.3 (20)

 discontinuation 0.2 (1) 0.9 (2) 0

iGlarLixi achieved significant HbA1c reductions, close to near normoglycemia without

increase in either hypoglycemia or weight, compared with iGlar, and had low gastrointestinal
adverse effects compared with Lixisenatide.

GI gastro-intestinal
LixiLan-O was a 30-week open-label, multicenter, randomized trial comparing iGlarLixi vs iGlar vs Lixi in adults with suboptimally controlled type 2 diabetes despite receiving
oral antihyperglycemic drugs (OADs)
Rosenstock J, et al. Diabetes Care 2016;39:2026−35
iGlarLixi achieved superior glycaemic control: post-hoc analysis

Study Objective: Assess efficacy and safety in patient subgroups:

• Baseline HbA1c ≥9% (n = 134)
• HbA1c ≥7.0%-≤9.0% despite two OADs at screening (n = 725)

Patients achieving HbA1c <7.0% at week 30

All patients Patients with baseline HbA1c ≥9.0% Patients with 2 OADs at
(range 9.0%-10.4%) screening
40.6%† 73.2%† 44.8%†
(95% CI: 33.63 to 47.59) (95% CI: 59.13 to 87.28) (95% CI: 35.92 to 53.63)
100 P<0.0001 100 P<0.0001 100 P<0.0001

90 90 90
14.3%† 26.7%† 14.6%†
(95% CI: 8.37 to 20.25) (95% CI: 8.80 to 44.61) (95% CI: 6.92 to 22.25)
80 P<0.0001 80 P=0.0064 80 P=0.0002

70 70 70

60 60 60
Patients (%)

Patients (%)

Patients (%)
50 50 50

40 40 40
73.7 73.5 72.4
30 59.4 30 30 57.8
47.3
20 20 20
33
27.6
10 10 10
0
0 0 0 0
N 468 466 233 N 49 55 29 N 290 287 145

iGlarLixi iGlar Lixisenatide

iGlarLixi is a viable treatment option for patients with T2DM who have HbA1c of 9% or who have failed to achieve glycaemic control with two OADs.

*Modified intent-to-treat population. †Overall LixiLan-O data based on mixed-effect model with repeated measures. ‡LS mean difference for iGlarLixi vs iGlar
or Lixi alone, ANCOVA; LOCF was used to handle missing data. ANCOVA, analysis of covariance; BL, baseline; LOCF, last observation carried forward.
Davies MJ et al. Diabetes, Obesity and Metabolism. 2019 Aug;21(8):1967-72.
LixiLan-O was a 30-week open-label, multicenter, randomized trial comparing iGlarLixi vs iGlar vs Lixi in adults with suboptimally controlled type 2 diabetes despite receiving oral antihyperglycemic drugs (OADs)
iGlarLixi allowed more patients intensifying either OADs or basal
insulin to achieve glycaemic control at early treatment time: post-hoc
analysis

Time to control was defined as days to achieve HbA1c <7% and was estimated using
the Kaplan–Meier method.

Time to achieve HbA1c <7%

HbA1c target was achieved by 50% of participants in

approximately half the time with iGlarLixi vs iGlar

100
iGlarLixi

uncontrolled following treatment,

according to HbA1c target (%)
80 iGlar

Participants remaining
166 days
60

40

85 days
20
HR: 1.5, p<0.0001
0
0 100 200 300
Time to first HbA1c <7% (days)

Efficacy, low rates of hypoglycaemia and the treatment simplicity with this combination may help to address clinical inertia and allow more patients
to safely reach their glycaemic targets earlier.

*Modified intent-to-treat population. †Overall LixiLan-O data based on mixed-effect model with repeated measures. ‡LS mean difference for iGlarLixi vs iGlar
or Lixi alone, ANCOVA; LOCF was used to handle missing data. ANCOVA, analysis of covariance; BL, baseline; LOCF, last observation carried forward.
Frias J et al. Diabetes, Obesity and Metabolism. 2018 Sep;20(9):2314-8.
LixiLan-O was a 30-week open-label, multicenter, randomized trial comparing iGlarLixi vs iGlar vs Lixi in adults with suboptimally controlled type 2 diabetes despite receiving oral antihyperglycemic drugs (OADs)
Phase III/IIIb evidence:
iGlarLixi in T2DM sub-optimally controlled on
OADs
• iGlarLixi vs IDegAsp
• iGlarLixi vs individual mono-components

iGlarLixi in T2DM sub-optimally controlled

on basal insulin
• iGlarLixi vs BIAsp30
• iGlarLixi vs iGlar
iGlarLixi in T2DM sub-optimally controlled on
GLP-1 RA
• Durability over 52 weeks
 SoliMix study: Phase 3b RCT comparing OD iGlarLixi vs BID BIAsp 30

Study Objective: Multicenter, open-label, randomized, 26-week, phase 3b study to

compare the efficacy and safety of iGlarLixi versus BIAsp 30 in adults with T2D advancing
from basal insulin + OADs (n = 887)

Population
Follow-up
A total of 887
• T2D for ≥1 year iGlarLixi once daily (n=443) (3 days) participants were
• ≥18 years of age Screening included from 89
• Basal insulin + OADs (1–2 weeks) centres across 17
(metformin ± SGLT2i) for BIAsp 30 twice daily (n=444) Follow-up
(3 days) countries
≥3 months
Open-label randomized treatment period
• HbA1c ≥7.5 % to ≤10.0 % (26 weeks)
• BMI ≥20 to <40 kg/m2 Randomization 1:1 India (n=182)
End of treatment
• Basal insulin dose at (Week 26)
screening ≥20 to ≤50 U

Prior OADs (metformin ± SGLT2i) were continued following randomisation.

BIAsp 30, biphasic insulin aspart 30 (30% insulin aspart and 70% insulin aspart protamine); BMI, body mass index, OAD, oral antihyperglycemic drug; U, units. Rosenstock J et al. Diabetes Care. 2021 Oct 1;44(10):2361-70.
 iGlarLixi showed superior HbA1c reduction and weight benefit versus
BIAsp30 (SoliMix Study)
Results
iGlarLixi was non-inferior* to BIAsp iGlarLixi was superior to BIAsp
HbA1c 30 in change in HbA1c from 30 in change in bodyweight from
baseline to Week 26 baseline to Week 26

iGlarLixi BIAsp 30 Mean ± SD bodyweight, iGlarLixi BIAsp 30

Mean ± SD HbA1c %
(n = 443) (n = 444) kg (n = 443) (n = 444)

Baseline 8.6 ± 0.7 8.6 ± 0.7 Baseline 80.7 ± 16.5 82.2 ± 18.5
LS mean ± SE change in HbA1c

Superiority (achieved)

LS mean ± SE change in bodyweight

Non-inferiority* (achieved)
from baseline to Week 26 (%)

LS mean difference (97.5% CI): LS mean difference (95% CI):

−1.3 ± 0.1 −1.1 ± 0.1 −0.2 (−0.4, −0.1) %; p<0.001 −1.9 (−2.3, −1.4) kg; p<0.001

from baseline to Week 26 (kg)

(%) (%)
+1.2 ± 0.2
Superiority (achieved) (kg)
LS mean difference (95% CI):
−0.2 (−0.4, −0.1) %; p<0.001

−0.7 ± 0.2
(kg)

Subsequent hierarchical testing showed superior HbA1c reduction with iGlarLixi vs BIAsp 30
*Non-inferiority margin 0.3 %.
CI, confidence interval; LS mean, least squares mean; SD, standard deviation; SE, standard error.
Rosenstock J et al. Diabetes Care. 2021 Oct 1;44(10):2361-70.
 Composite target achievement was significantly greater with iGlarLixi, and
smaller mean daily insulin dose required with iGlarLixi versus BIAsp 30 (SoliMix)
Secondary Endpoints Total insulin daily dose

iGlarLixi BIAsp 30 OR*(95% CI) LS mean difference iGlarLixi vs BIAsp

(ITT population; n=443) (ITT population; n=444)
30 (95% CI)
−12.2 (−14.8, −9.7) U

daily dose from baseline to Week 26, U

40

LS mean ± SE change in total insulin

27.5 (n=122)
HbA1c <7 % without 35
3 2.83 (1.98, 4.04)
weight gain‡
(Key secondary endpoint)
30 +22.9
12.4 (n=55) p<0.001 25 ± 1.1
20
15
+10.6
HbA1c <7 % without 19.4 (n=86) ± 1.2
10
weight gain and2 3.40 (2.19, 5.28)
without hypoglycemia# 5
(Key secondary endpoint) 7.0
(n=31) p<0.001 0
Series1

42.2 (n=187)
HbA1c <7 %1 Mean ± SD total iGlarLixi BIAsp 30
1.65 (1.25, 2.19)† insulin daily dose, U (n=442) (n=441)
(Exploratory analysis ) †

31.8 (n=141) Baseline 26.4 ± 6.2 33.6 ± 11.0

Week 26 39.7 ± 12.0 58.2 ± 23.6

0 10 20 30 40 50

CI, confidence interval; ITT, intent-to-treat; OR, odds ratio; U, units.

*Adjusted OR of iGlarLixi vs. BIAsp 30 with associated two-sided CI (at the specified significance level that is passed from family 1 of the primary objectives), calculated by logistic regression model adjusted for fixed
categorical effects of randomization strata (basal insulin dose at screening <30 units and ≥30 units and SGLT2i use [yes, no] at screening) and treatment group as well as fixed continuous covariates of baseline values for
each of the primary end points (HbA1c and body weight; ‡Weight gain defined as any increase >0 kg from baseline; #Hypoglycemia defined as plasma glucose <70 mg/dL occurring at any point within the 26-week open-
label randomized treatment period; †not included in the multiple testing procedure. Rosenstock J et al. Diabetes Care. 2021 Oct 1;44(10):2361-70.
Lower risk of hypoglycaemia at any time of day with iGlarLixi versus
BIAsp30 (SoliMix study)
Hypoglycemia
iGlarLixi (Safety population; n=442) BIAsp30(Safety population; n=441)

Incidence of hypoglycemia, % (n) Incidence of nocturnal hypoglycemia, % (n)

Any hypoglycemia ADA Level 1 ADA Level 2 ADA Level 1 ADA Level 2

Between 0:00-06:00 Between 0:00-06:00

Relative odds reduction
20 with iGlarLixi vs BIAsp30

Incidence, % (n)
Relative odds reduction with iGlarLixi vs BIAsp 30 OR (95% CI)
8.8% 0.32 (0.12, 0.90)
(n=39)
5.4%
10
−38% −45% −55% (n=24) 1.1% 3.4%
(n=15)
(n=5) -68%
OR (95% CI):
†
OR†(95% CI):
OR†(95% CI):
0.62 (0.47, 0.81) 0.45 (0.28, 0.73) 0
0.55 (0.42, 0.74)
50
Between bedtime and waking Between bedtime and waking
40
42.4%
Incidence, % (n)

(n=187) 20
30 14.5% OR (95% CI)
38.5%

Incidence, % (n)
31.2%
11.3% (n=64)
(n=170) 0.37 (0.16, 0.84)
(n=138) (n=50)
20
25.8% 10
(n=114) 1.8% 4.8% -63%
6.3%
10 (n=8) (n=21)
(n=28) 12.9%
(n=57)
0
0
Series1 Series1 Series1

Three sever hypoglycemic episodes (ADA Level 3*) were reported: one in the iGlarLixi group and two in the BIAsp 30 group

†OR for iGlarLixi vs. BIAsp 30 and 95% CI based on logistic regression with treatment group (iGlarLixi and BIAsp 30) and randomization strata (HbA1c <8.0% and $8.0%, basal insulin dose at
screening <30 units and $30 units, and SGLT2 inhibitor use [yes, no] at screening) as fixed effects . *Defined as severe cognitive impairment requiring external assistance for recovery.
ADA, American Diabetes Association; CI, confidence interval; OR, odds ratio. ADA Level 1; <70 mg/dL and ≥54 mg/dL, ADA Level 2; <54 mg/dL McCrimmon RJ et al. Diabetes, Obesity and Metabolism. 2022 Dec;24(12):2391-9. ;
Rosenstock J et al. Diabetes Care. 2021 Oct 1;44(10):2361-70.
iGlarLixi vs BIAsp 30 (SoliMix Study): Summary & Conclusion

Efficacy

Safety
Efficacy
• iGlarLixi vs BIAsp 30
 Better glycemic control with weight benefit
 Less hypoglycemia
 Fewer daily injections
 Similar proportion of SAEs in both treatment groups

• iGlarLixi is an efficacious, simpler, and well-

tolerated alternative to premix BIAsp 30 in uncontrolled
T2D.
Safety

SAE; serious adverse event

Rosenstock J et al. Diabetes Care. 2021 Oct 1;44(10):2361-70.
Once daily iGlarLixi vs twice daily BIAsp 30 (SoliMix study):
Patient-reported outcomes (PROs)

PROs were assessed using the Treatment-Related Impact Measure Diabetes (TRIM-D) and
Global Treatment Effectiveness Evaluation (GTEE) questionnaires

Participants receiving iGlarLixi perceived a complete or marked improvement in diabetes control compared
with those receiving BIAsp 30:

iGlarLixi: 81% BIAsp 30: 63%

This perception
was also shared by
the doctors who
treated them.

Increase of
High scores mean: 11 points In addition to better glucose control, weight
More treatment
satisfaction Low scores mean: benefit and less hypoglycaemia, once daily
Less treatment Increase of Less treatment iGlarLixi provided improved diabetes
burden 6 points satisfaction management, treatment burden and
More treatment
perceived effectiveness versus twice-daily
burden
iGlarLixi BIAsp 30 premix BIAsp30.

Polonsky WH et al. Diabetes, Obesity and Metabolism. 2022 Dec;24(12):2364-72. DOM-24-2364-s002.pdf

Phase III/IIIb evidence:
iGlarLixi in T2DM sub-optimally controlled on
OADs
• iGlarLixi vs IDegAsp
• iGlarLixi vs individual mono-components

iGlarLixi in T2DM sub-optimally controlled

on basal insulin
• iGlarLixi vs BIAsp30
• iGlarLixi vs iGlar
iGlarLixi in T2DM sub-optimally controlled on
GLP-1 RA
• Durability over 52 weeks
iGlarLixi vs iGlar in basal uncontrolled patients:
LixiLan-L study

Study Objective: Randomized, open-label, parallel-group phase III study to assess

superiority of iGlarLixi over iGlar in HbA1c change from baseline to Week 30 (n = 736)

People with T2D

iGlar + metformin
iGlar introduced n=369
• Receiving basal insulin (iGlar, detemir, NPH) for
and/or titrated
>6 months ± OADs
R
• Stable basal insulin dose (15–40 U/day) for >2 Run-in phase 6 iGlarLixi + metformin
months weeks
n=367
• HbA1c ≥7.5%–10%
• FPG ≤140 mg/dL at the end of run-in 30 weeks

iGlarLixi was self administered 0-60 minutes before breakfast

U, units, OD, once daily; QW, once weekly, BD, twice daily, ER, extended release
Aroda VR, et al. Diabetes Care 2016;39:1972–80
iGlarLixi demonstrated superior HbA1c reduction and significant
reduction in average 7-point SMPG (LixiLan-L study)
HbA1c reduction Average 7-point SMPG profile
Baseline 8.1 ± 0.7 8.1 ± 0.7 iGlarLixi at baseline iGlar at baseline
0.0
iGlar at week 30
Series1 iGlarLixi at week 30

-0.2
LS mean change (%)

-0.4
–0.6
-0.6

-0.8
iGlarLixi (n=367)
-1.0 iGlarLixi
–1.1 iGlar
-1.2 iGlar (n=369)
–0.5
95% CI: –0.6, –0.4
p<0.0001 2-hour PPG reduction

FPG reduction 2-hour PPG reduction

Baseline 132 ± 35 132 ± 37 Baseline 268 ± 69 270 ± 66
0 0.0
Series1 -10.0 Series1
-2
-20.0 -25.1

LS mean change (mg/dL)

LS mean change (mg/dL)

-4 -30.0
-6
-6 -40.0
-8 -50.0
-8
-60.0
-10
-70.0
–60.0
-12 -80.0 -85.1
2 95% CI: –70.1, –50.0
-90.0 p<0,0001
95% CI: –3.6, 7.2
p=0.495

Dose if insulin glargine at week 30: iGlarLixi group: 46.7±12.6U; iGlar group: 46.7±12.5 U
‡Documented symptomatic hypoglycemia, defined as plasma glucose ≤70 mg/dL Aroda VR, et al. Diabetes Care 2016;39:1972–80
 Significantly higher proportion of patients treated with iGlarLixi
reached HbA1c targets of <7% (LixiLan-L study)

Individuals at target HbA1c Weight change Hypoglycemia‡

25.5 Baseline 87.7 87.1
70 95% CI: 18.9, 32.1 Individuals with No. of events per
Proportion of individuals

p<0.0001 1.0 events (%) patient year

60 50 5.0
19.8

LS mean change (kg)

50 55 95% CI: 13.9, 25.6 0.7
40 4.0
p<0.0001
40 0.0 42.5 4.2
(%)

Series1 30 40.0 3.0

30 34
30 3.0
20 20 2.0
-1.0
10 14 –0.7 10 1.0
–1.4
0 95% CI: –1.8, –0.9
HbA1c <7% HbA1c ≤6.5% -2.0 p<0.0001 0 0.0
Series1 Series1

Higher proportion of iGlarLixi-treated patients achieved glycemic targets with a beneficial effect
on body weight, no additional risk of hypoglycemia, and low levels of GI adverse effects compared
to iGlar in basal uncontrolled long-standing T2DM.

‡Documented symptomatic hypoglycemia, defined as plasma glucose ≤70 mg/dL

§Severe hypoglycemia was reported in 4 (1.1%) individuals in the iGlarLixi group and 1 (0.3%) individual in the iGlar group
Aroda VR, et al. Diabetes Care 2016;39:1972–80
Phase III/IIIb evidence:
iGlarLixi in T2DM sub-optimally controlled on
OADs
• iGlarLixi vs IDegAsp
• iGlarLixi vs individual mono-components

iGlarLixi in T2DM sub-optimally controlled on

basal insulin
• iGlarLixi vs BIAsp30
• iGlarLixi vs iGlar
iGlarLixi in T2DM sub-optimally controlled
on GLP-1 RA
• Durability over 52 weeks
Durable effects of iGlarLixi up to 52 weeks in type 2 diabetes:
LixiLan-G extension study

LixiLan-G was a randomized, controlled, open-label 26-week, study comparing iGlarLixi with prior GLP-1 RA regimen.
LixiLan-G extension study is a 26-week, single-arm extension of LixiLan-G to determine the durability of iGlarLixi
efficacy and safety over 52 weeks.

Baseline to Baseline to
People with T2D
Week 26 Week 52
 Adults with T2DM ≥1 year Mean ± SD
GLP-1 RA iGlarLixi iGlarLixi
 HbA1c 7% to 9% reduction in
 OADs (metformin ± pioglitazone ± SGLT2 inhibitor) -0.4 -1.0 -1.0
 GLP-1 RA (liraglutide once daily, or exenatide twice daily for ≥4 months, HbA1c ± 0.8 ± 0.9 ± 0.9
exenatide ER, albiglutide, or dulaglutide once weekly for ≥6 months)
(%)

Randomized treatment period Extension period -13.5 -38.6 -40.9

FPG ± ± ±
(n=206) (mg/dL) 44.5 41.8 43.5
(n=257)
iGlarLixi (once daily) iGlarLixi (once daily)
R -21.5 -70.6 -77.4
1:1 (n=257)
2-hr PPG ± ± ±
Continued previous GLP-1 RA 66.4 68.6 71.0
(mg/dL)
Baseline OADs were continued without modification
(metformin ± pioglitazone ±SGLT2 inhibitor)

Week 0 Week 52 2-hr -9.1 -28.0 -33.4

Week 26
Inclusion criteria for extension period: plasma ± ± ±
No rescue therapy OR Rescue therapy but
HbA1c ≤8% at Week 12
Glucose 50.6 58.0 52.1
AND
No discontinuation of iGlarLixi before Week 26
excursio
n*
*2-hr plasma glucose excursion is defined as change in plasma glucose concentration from before a meal to 2 hours after a meal. (mg/dL) Blonde L et al. Diabetes Care. 2021 Mar 1;44(3):774-80.
Durable effects of iGlarLixi up to 52 weeks in type 2 diabetes:
LixiLan-G extension study

Results at week 26 were also maintained at week 52 Safety results for iGlarLixi over 52 weeks were similar
for target achievement endpoints: to those seen over 26 weeks

At week 26 At week 52 Week 0-26 Week 0-52

Percentage at target GLP-1 RA IGlarLixi IGlarLixi IGlarLixi IGlarLixi

Any AE 64% 73%

HbA1c <7%
26% 62% 64%
Any GI disorder 22% 25%

Documented symptomatic
HbA1c <7% with no (≤3.9 mmol/L) hypoglycemia 1.54 1.59
documented events PPY
symptomatic 25% 57% 58%
(<54 mg/dL) Documented symptomatic
hypoglycemia (<3.0 mmol/L) hypoglycemia 0.25 0.24
events PPY

The efficacy and safety of iGlarLixi at the end of the 26-week randomized treatment period were maintained at week 52.

Blonde L et al. Diabetes Care. 2021 Mar 1;44(3):774-80.

iGlarLixi
CV Safety
ORIGIN: Basal Insulin Glargine and Cardiovascular Outcomes

ORIGIN trial assessed the effects of insulin glargine vs. standard care on CV outcomes in people with
CV risk factors + impaired fasting glucose/impaired glucose tolerance/or T2D (N=12,537)

MI, stroke, or death from CV Causes (coprimary outcome)

0.6
Adjusted HR: 1.02 (0.94-1.11)
P=0.63 by log-rank test
Over the more than 6 years follow-up of 0.4

Proportion with
the ORIGIN study, key findings are:
0.3

events
 Insulin glargine had a neutral effect on
CV outcomes 0.2 Insulin glargine
 Rates of incident CV outcomes were similar in
insulin glargine and standard-care groups 0.1
Standard care
(2.94 and 2.85 per 100 person-years,
respectively) 0.0
0 1 2 3 4 5 6 7
Years of follow-up
No. at risk
Insulin glargine 6264 6057 5850 5619 5379 5151 3611 766
Standard care 6273 6043 5847 5632 5415 5156 3639 800

CV, cardiovascular; HR, hazard ratio; ORIGIN Trial Investigators. New England Journal of Medicine. 2012 Jul 26;367(4):319-28.
ELIXA: Lixisenatide in Patients with T2D & Acute Coronary Syndrome

ELIXA was a randomized, double-blind, placebo-controlled, parallel-group, multicenter phase III event-
driven trial that assessed the effect of lixisenatide when added to standard T2DM therapy on CV
morbidity and mortality in patients with a recent ACS (N=6,068)

Study included participants with: Kaplan–Meier plot of the first confirmed primary endpoint event
 Established or newly diagnosed T2DM (HbA1c:
7.7%)
20
 High risk of CVD* HR (95% CI): 1.02 (0.89, 1.17)

incidence (%)
15

Cumulative
After a median follow-up of 25 months, 10
lixisenatide demonstrated:
Placebo
 Non-inferiority vs placebo for composite primary 5 Lixisenatide
CV endpoint†
 Neutral effect on the individual components of
0
the composite primary and secondary CV 0 12 24 36
endpoints No. at risk
 No increase in HF risk Placebo 3034 2759 1566 476
Lixisenatide 3034 2785 1558 484

*ACS event within 180 days of screening, MI or unstable angina. †Composite of the first occurrence of any of the following: death from CV causes, nonfatal MI, nonfatal stroke, or hospitalization for unstable angina.
ACS, acute coronary syndrome; CV, cardiovascular; HbA1c, glycated hemoglobin; HF, heart failure; HR, hazard ration; MI, myocardial infarction; T2DM, type 2 diabetes mellitus. Pfeffer MA et al. NEJM 2015;373:2247–57.
iGlarLixi
o Pen
o Dose
o Titration
o Use in special population
iGlarLixi 10-40 Pen
10–40 Pen
(2 U:1 µg ratio)
Insulin Lixisenati
glargine de
10 U 5 mcg
11 5.5
12 6
13 6.5
Per mL: 100 units/mL + 50 µg/mL 14 7
15 7.5
16 8
Composition Total 3 mL: 17 8.5
18 9
300 units of insulin glargine & 19 9.5
20 10
150 µg lixisenatide
21 10.5
22 11
23 11.5
Lixisenatide concentration 50 µg/mL
24 12
25 12.5
26 13
Ratio Glargine: lixisenatide 2 U : 1 µg 27 13.5
28 14
29 14.5
Dose range 10 dose to 40 dose 30 15
31 15.5
32 16
33 16.5
34 17
35 17.5 Dose starts
36 18 with zero
37 18.5
38 19
Lixisenatide dose follows the insulin glargine 100 U/mL dose
39 19.5
40 U 20 mcg
Soliqua® SoloStar® PI.pdf (sanofi.in) Accessed on 1July2024
 iGlarLixi: Dose and Dose Titration

Dose must be individualized based on fasting plasma glucose and titrated in accordance
with individual patient needs

Previous therapy

Insulin naïve patients

Insulin glargine Insulin glargine
(Oral anti-diabetic
(U100)* (U100)*
treatment or
<20 U ≥20 and <30 U
GLP-1RA)

Starting iGlarLixi 10 dose steps 20 dose steps

dose (10–40) pen (10 U/5 µg) (20 U/10 µg)

Weekly dose adjustment based on mean fasting SMPG from the last 3 days

The starting dose of iGlarLixi should not exceed the recommended lixisenatide starting dose of 10 mcg.
*If a different basal insulin was taken:
For twice daily basal insulin or glargineU300, the total daily dose previously taken should be reduced by 20% to choose the iGlarLixi starting dose.
For any other basal insulin the same rule as for insulin glargine (U100) should be applied.

Soliqua® SoloStar® PI.pdf (sanofi.in) Accessed on 1July2024

 iGlarLixi: Dose Titration

i G l a rLi xi : D ose Ti tra ti on *

+4
Timing of iGlarLixi- Within

iGlarLixi should be injected subcutaneously

Dose change

+2 once a day within 1 hour prior to a meal

<80
It is preferable that the prandial injection is
No change mg/dL performed before the same meal every day,
Fasting >140 >100 & ≤140 80-100 when the most convenient meal has been
mg/dL
SMPG mg/dL mg/dL
chosen

In case of missed dose, it should be injected

-2 within the hour prior to the next meal.

*Dose must be individualized based on individual patient needs and conditions

Weekly dose adjustment based on mean fasting SMPG from the last 3 days

Soliqua® SoloStar® PI.pdf (sanofi.in) Accessed on 1July2024

 iGlarLixi: Usage in Special Population

Elderly
(≥65 years old)
Renal
impairment
Hepatic
impairment
04 Pregnancy

iGlarLixi can be iGlarLixi can be used in iGlarLixi can be used in iGlarLixi should not be
used in elderly patients with mild or patients with hepatic used during pregnancy.
patients moderate renal impairment The potential risk for
impairment humans is unknown.
For lixisenatide, no For lixisenatide, no
dose adjustment is iGlarLixi is not dose adjustment is If a patient wishes to
required based on recommended in required in patients become pregnant, or
age patients with severe with hepatic pregnancy occurs,
renal impairment impairment treatment with iGlarLixi
(creatinine clearance should be discontinued.
<30 mL/min) or end-
stage renal disease

In each of these populations: Insulin requirements More frequent glucose monitoring and
may be reduced dose adjustment may be necessary

Soliqua® SoloStar® PI.pdf (sanofi.in) Accessed on 1July2024

SUMMARY
iGlarLixi 10-40 Pen

One injection

Once daily
Within

One hour prior to meal

Soliqua® SoloStar® PI.pdf (sanofi.in) Accessed on 1Julyl2024

 Combination Injectable iGlarLixi

iGlarLixi is a synergistic once daily combination injectable of basal insulin glargine U100 and

prandial GLP-1RA lixisenatide that provides effective fasting and post-prandial glycemic control.

Soli-D trial indicates that iGlarLixi is a simple, well-tolerated treatment that has shown better
glycaemic control with added body weight benefit and lower risk of hypoglycaemia events
compared with IDegAsp.

SoliMix trial indicates that the iGlarLixi is efficacious, simpler, well-tolerated, provided better
glycemic control with weight benefit, and less hypoglycemia compared with twice daily
BIAsp30.
Thank You
BACK UP
SLIDES
iGlarLixi vs iGlar vs Lixisenatide in OAD Uncontrolled Patients:
(LixiLan-O study) Baseline data

iGlarLixi iGlar Lixisenatide All

(n=469) (n=467) (n=234) (N=1170)

Age, years 58.2 ± 9.5 58.3 ± 9.4 58.7 ± 8.7 58.4 ± 9.3

Male/female, % 47.3/52.7 50.7/49.3 56.8/43.2 50.6/49.4

Demographics and
Diabetes duration, years 8.9 ± 5.5 8.7 ± 5.6 8.9 ± 6.3 8.8 ± 5.7 baseline characteristics
were similar across the
BMI, kg/m2 31.6 ± 4.4 31.7 ± 4.5 32.0 ± 4.4 31.7 ± 4.4
treatment groups
Individuals with BMI ≥30 62.9 61.7 67.9 63.4
HbA1c at baseline,% 8.1 ± 0.7 8.1 ± 0.7 8.1 ± 0.7 8.1 ± 0.7
Individuals with HbA1c ≥8%, % 55.9 55.7 56.0 55.8
Patients had-
FPG, mmol/mol 9.9 9.8 9.8 9.8
o Average age of 58 years
Metformin dose at baseline, mg 2246 (457) 2245 (445) 2267 (427) 2250 (446) o Overweight or obese
Second OAD use at screening, % 58.4 57.8 56.8 57.9 (BMI~32 kg/m2)
Sulfonylurea 55.2 53.3 52.6 53.9 o Mean duration of
diabetes of~9 years
Glinide 0.6 2.1 2.1 1.5
SGLT-2 inhibitor 0.4 0.4 0 0.3
DPP-4 inhibitor 2.6 2.4 2.1 2.4

Data is represented as mean ± SD, n (%), or %.

Rosenstock J, et al. Diabetes Care 2016;39:2026−35
iGlarLixi vs BIAsp30 in basal uncontrolled patients:
(SoliMix study) Baseline data

iGlarLixi BIAsp 30 All randomized

(n=443) (n=444) participants (N=887)
Age, years
59.8 ± 10.3 59.8 ± 10.0 59.8 ± 10.2

Sex, female 219 (49.4) 226 (50.9) 445 (50.2)

BMI, kg/m2 29.7 ± 4.7 30.0 ± 5.1 29.9 ± 4.9 Demographics and baseline
70 (15.8) 78 (17.6) 148 (16.7)
<25
characteristics
≥25 to <30 180 (40.7) 165 (37.2) 345 (38.9)
≥30 to <35 125 (28.3) 112 (25.2) 237 (26.7) were similar across both
≥35 67 (15.2) 89 (20.0) 156 (17.6) treatment group
Duration of T2D, years 13.0 ± 7.1 13.0 ± 7.4 13.0 ± 7.2

HbA1c, % 8.6 ± 0.7 8.6 ± 0.7 8.6 ± 0.7

Average basal insulin daily

dose†, U 33.8 ± 9.6 33.8 ± 9.9 33.8 ± 9.8 Metformin was used at
Prior basal insulin at baseline, n (%)*
baseline in 99.8% of all
Insulin glargine 100 units/mL 188 (42.4) 219 (49.2) 407 (45.8) participants
Insulin glargine 300 units/mL 100 (22.6) 92 (20.7) 192 (21.6)
NPH 102 (23.0) 82 (18.4) 184 (20.7)
Insulin detemir 34 (7.7) 31 (7.0) 65 (7.3)
Insulin degludec 19 (4.3) 21 (4.7) 40 (4.5)

SGLT2i use
104 (23.5) 102 (23.0) 206 (23.3)
at screening*

Data shown are mean ± SD or n (%). *A participant can be counted in more than one category. †Average daily basal insulin dose at baseline
within 3 days immediately before randomization.; SD, standard deviation; U, units. Rosenstock J et al. Diabetes Care. 2021 Oct 1;44(10):2361-70.
iGlarLixi vs iGlar basal uncontrolled patients:
(LixiLan-L study) Baseline data

iGlarLixi iGlar
(n=469) (n=467)
Age, years 59.6 ± 9.4 60.3 ± 8.7
Male/Female, % 45.0/55.0 48.5/51.5
Body weight at baseline, kg 87.7 ± 14.5 87.1 ± 14.8
BMI at baseline, kg/m2 31.3 ± 4.3 31.0 ± 4.2
Diabetes duration, years 12.0 ± 6.6 12.1 ± 6.9
Demographics and
Duration of basal insulin treatment, years 3.1 ± 3.1 3.3 ± 3.1 baseline characteristics
Basal insulin type at screening, % were similar across the
iGlar 64 65 treatment groups
Insulin detemir 13 15
NPH 23 20
OAD use at screening, %
None 5 5
Metformin 46 52 Patients had-
SU 4 4 o Average age of 60 years
DPP-4 inhibitor 1 1 o Overweight or obese
Metformin + SU 37 32
Metformin + DPP-4 inhibitor 5 5
(BMI~31 kg/m2)
HbA1c, % o Mean duration of
Screening 8.5 ± 0.7 8.5 ± 0.7 diabetes of~12 years
Baseline 8.1 ± 0.7 8.1 ± 0.7
FPG, mmol/L
Screening 7.9 ± 1.8 8 ± 1.8
Baseline 7.3 ± 2.0 7.4 ± 2.1

Data is represented as mean ± SD, n (%), or %.

Aroda VR, et al. Diabetes Care 2016;39:1972–80