®

Should ultra-rapid acting

analogs be the new standard
of mealtime insulins care?
3 May 2023

Dr Hood Thabit Prof Christophe De Block

Consultant diabetologist and senior lecturer Endocrinology-Diabetology
Manchester University Hospital Foundation Trust, UK Antwerp University Hospital, Belgium

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Mealtime insulin dosing
Current barriers
Prof Christophe De Block
Disclosures

Prof De Block

• Advisory board

– Abbott Diagnostics, AstraZeneca, Boehringer-Ingelheim,

Eli Lilly, Insulet, Novo Nordisk

• Research support

– AstraZeneca, Boehringer-Ingelheim, Indigo nv, Novo Nordisk

• Speaker bureaus

– Eli Lilly, Novo Nordisk, Abbott Diagnostics

 Current reality of diabetes healthcare gap with mealtime insulin
Patients lack confidence around mealtime insulin

35%
‘very
confident’

Although the majority of T1DM patients recognise the importance of accurate mealtime insulin bolus
dosing, only a small proportion (35%) report being ‘very confident’ in accurate bolus insulin estimation

T1DM = type 1 diabetes mellitus.

Lane W, et al. Clin Diabetes. 2021;39(4): 347–357.
 Mealtime insulin: Mismatch between recommendation and reality
• PPG contributes significantly to HbA1c1
• Mismatch between insulin action and PPG elevations could result in elevated HbA1c 2
Mean fasting and 2-hr plasma glucose levels in US adults
aged 40–74 years with T2DM not using insulin1
600
Plasma glucose (mg/dL)

500

400

300

200

100

0
<7 7–7.9 8–8.9 9–9.9 ≥10

HbA1c (%)

Fasting plasma glucose 2-hour plasma glucose

HbA1c = glycated haemoglobin; hr = hour; PPG = postprandial glucose; T2DM = type diabetes mellitus.
1
Modified according to Erlinger TP and Brancati FL. Diabetes Care. 2001;24(10): 1734–1738. 2Datye KA, et al. J Diabetes Sci Technol. 2018;12(2): 349–355.
 Mealtime insulin: Mismatch between recommendation and reality

Time of mealtime insulin injection1

21%
24%

• Hypoglycaemia is less likely in those who

dosed insulin before meals than those who
10% dosed at or after meals2

44%

Before meal At meal During meal After meal

Currently available rapid-acting insulin analogues (e.g. insulin lispro, insulin aspart) are recommended to
be injected 15–20 minutes prior to meal consumption in order to provide optimal PPG control. 3
PPG = postprandial glucose.
1
Modified according to Datye KA, et al. J Diabetes Sci Technol. 2018;12(2): 349–355. 2Tamborlane WV, et al. Curr Med Res Opin. 2017;33(4): 639–645. 3Slattery D, et al. Diabet Med. 2018;35(3): 306–316.
 Need for faster-acting insulin
Current fast-acting insulin
analogues
Sun 8 Jan 249
• Onset of glucose-lowering takes
>10 min1,2 10
1
• Maximum insulin concentrations Glucose
mg/dL
are not reached until 60 min 121 101

after injection3
Carbs
• To achieve optimal PPG control, Grams

Rapid-acting
patients are forced to wait 15 to insulin 5.0 8.0
20 min post-injection before a Units

meal4 Long-acting insulin

Units
15.0

• This affects quality of life and

flexibility4

Current fast-acting insulin is still not fast enough 1-4

Carbs = carbohydrates; PPG = postprandial glucose.
1
Sanlioglu AD, et al. Islets. 2013;5(2): 67–78. 2Shiramoto M, et al. J Diabetes Investig. 2018;9(2): 303–310. 3Slattery D, et al. Diabet Med. 2018;35(3): 306–316. 4Heinemann L and Muchmore DB.
J Diabetes Sci Technol. 2012;6(4): 728–742.
 People with T2D may spend >12 hours per day in the postprandial state
Duration of postprandial state

Breakfast Lunch Dinner Midnight 4 AM Breakfast

8 AM 11 AM 2 PM 5 PM

Postprandial Postabsorptive Fasting

T2D = type 2 diabetes.
Modified according to Monnier L. Eur J Clin Invest. 2000;30(Suppl 2): 3–11.
 Missed mealtime doses may translate to poor glycaemic control
• We spend 12 hours of every day in a post-prandial state1
• A study found a nearly 1% increase in HbA1c per week for every four mealtime doses missed2

4
missed
mealtime
doses
0.92%
increase
in
HbA1c

In a 2006 survey of youth with T1DM using CSII with suboptimal HbA1c levels ≥8 (n = 48) in the USA,
linear regression showed a 0.92% increase in HbA1c for every four meal boluses missed at 3 months 2

CSII = continuous subcutaneous insulin infusion; HbA1c = glycated haemoglobin; PPG = post-prandial glucose; T1DM = type 1 diabetes mellitus.
1
Monnier L, et al. Diabetes Metab. 2004;30(2): 113–119. 2Chase HP, et al. Diabetes Care. 2006;29(5): 1012–1015.
 Possible complications for poor PPG control

1 Increased risk of retinopathy

2 Increased carotid intima-media thickness

3 Independent risk factor for macrovascular disease

4 Decreased myocardial blood volume and blood flow

5 Oxidative stress, inflammation and endothelial

dysfunction

PPG = postprandial glucose.

Ceriello A, et al. Nutr Metab Vardiovasc Dis. 2008;18(4): S17–33.
 Main physician barriers to insulin intensification
600 physicians from Germany, Japan, Spain, Turkey, the UK, and the USA were recruited to complete an online survey 

Doctors are lacking experience with the available insulins

Doctors feel that educating patients about insulin intensification will take too much time

Doctors do not believe that patients will be able to cope with intensified insulin therapy

Guidance about insulin intensification is lacking

Monitoring to show when patients with T2DM require intensified therapy is lacking

Doctors lack belief that insulin intensification is necessary

[USA, Spain, Japan only; n = 300]: The reimbursement situation for insulin

Other

There are no barriers to insulin intensification in my country

0% 10% 20% 0 30% 2040% 4050% 6060% 8070% 100
80% 90% 100%

Percentage of respondents

T2DM = type 2 diabetes mellitus.

Modified according to Cuddihy RM, et al. Diabetes Educ. 2011;37(1): 111–123.
 Primary care physician-perceived barriers to insulin therapy
288 physicians from 168 primary healthcare centers in the Jazan region of Saudi Arabia

For most of my patients, these are the biggest barriers Total Practitioner Specialist
p
to their acceptance of insulin therapy n = 288 n = 202 n = 86

Fear of injection 80.6 79.2 83.7 0.376

Lack of education about diabetes and insulin 68.8 69.3 67.4 0.755
Fear of hypoglycaemia 50.7 48.5 55.8 0.257
Technical difficulty in insulin administration 50.7 46.5 60.5 0.030*
Concern about personal failure in controlling diabetes 26.4 18.8 44.2 <0.001*
Embarrassment/social stigma 16.7 14.9 20.9 0.205
Fear of weight gain 14.6 12.9 18.6 0.207
Religious/cultural beliefs 11.1 11.9 9.3 0.524
Fear of death 10.4 8.9 14 0.200
Worry about job instability 8.3 5.9 14 0.024*
Decreased life span 6.3 2.0 16.3 <0.001*
Insulin cost 4.9 4 7 0.276

Data are presented as a percentage; *p is significant at the 0.05 level.

Alhagawy AJ, et al. Int J Environ Res Public Health. 2022;19(24): 16794.
 The patient difficulty most often reported by physicians was
that the typical patient finds it difficult to take insulin frequently
70%
58.5% 57.7% 54.5%
60%
Internet survey of 1250 physicians: 50%
*1
45.4%
40% 35.0%
30%
• 600 specialists 20%

Physicians (n=1250)
10%
0%
• 650 primary care physicians who ent
ly
eed
s
da
ily
t io
ns
t io
ns
qu n ls ru
c
je
c
treat patients with diabetes in
fre dai
ly
m
ea
inst g
in
s ul ee
t ith P arin
w C
in m or H ep
in
g to e in
g Pr
• from China, France, Japan, Ta
k
s ul
in tim llo
w
in ed Fo
Germany, Spain, Turkey, the UK of c rib
g
in r es
m
or the USA ng
ti
th
e
p

ngi at
ha lin
C
nsu
i
g
k in
Ta

Patient difficulties*

*Very difficult or somewhat difficult (vs. very easy, somewhat easy, not applicable, ‘don’t know’). * 1Physician item is ‘taking insulin frequently’.
HCP = healthcare professional.
Modified according to Peyrot M, et al. Diabet Med. 2012;29(5): 682–689.
 The difficulty most often reported by insulin-treated patients
was taking insulin at the prescribed time or with meals
30% 27.6%
*1
25% 23.1%
20% 16.9% 16.8%
15%
10.3%
10%
5%
Patients (n = 1530)

0% Telephone survey of 1530 patients

-5%
receiving insulin (180 with T1DM,
1350 with T2DM) in China, France,
Japan, Germany, Spain, Turkey, the
UK or the USA

Patient difficulties*

*Very difficult or somewhat difficult (vs. very easy, somewhat easy, not applicable, ‘don’t know’). * 1Average of response for two items (insulin at prescribed times, insulin with each meal).
HCP = healthcare professional; T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus.
Modified according to Peyrot M, et al. Diabet Med. 2012;29(5): 682–689.
 Reasons* for insulin omission/non-adherence,# as reported by
patients (n = 530) and physicians (n = 964)

Patients Physicians
Too busy
Reason
Travelling % Rank % Rank

Skipped a meal Too busy 18.9 1 41.9 3

Stress or emotional problems Traveling 16.2 2 43.6 2

Injection embarassment Skipped meal 15.0 3 44.8 1

Challenging to take at the same time every day Stress or emotional problems 11.7 4 32.2 5

Forgot Embarrassing to inject in public 9.7 5 36.8 4

Too many injections Challenging to take it at the same

9.4 6 29.1 6
time every day
Avoid weight gain
Forgot 7.4 7 2.0 11
Regimen is too complicated
Too many injections 6.0 8 26.4 7
Injections are too painful
Avoid weight gain 4.0 9 13.4 9
0 5 10 15 20
Regimen is too complicated 3.8 10 16.8 8
Patients (%) Injections are painful 2.6 11 7.8 10

*Respondents were asked to select top three reasons (order of reasons randomised, ‘forgot’ responses volunteered as ‘other’); data are percentage of respondents choosing a reason as one of the three.
#Absolute percentages reported for physicians cannot be compared with percentage of patients who report these reasons because physicians report whether this is a reason for the behaviour of their
‘typical patient’ rather than the percentage of their patients for whom this is a reason; rank order of reasons by patients and physicians can be compared.
Modified according to Peyrot M, et al. Diabet Med. 2012;29(5): 682–689.
 Objectives of developing a new mealtime insulin

Targeted action profiles of potential

future mealtime insulins

Improve PPG
More rapid absorption after injection

Faster onset of action

Possibility of flexible mealtime dosing

Greater potential for early

glucose lowering
Improve the profile for pumps
without late postprandial or nocturnal
hypoglycaemia

… compared with currently

available mealtime insulins

PPG = postprandial glucose.

Ziegler R, et al. Journal of Diabetes Science and Technology. 2017;11(1): 165–171.
 Evolution of mealtime bolus insulin

Faster-
Insulin Insulin Insulin acting
regular lispro glulisine insulin
aspart

198 199 199 200 200 201 201 202

3 1 6 2 4 7 7 0

Insulin
Insulin Insulin Insulin
lispro-
regular aspart lispro
aabc

Modified according to Wong EY and Kroon L. Clin Diabetes. 2021;39(4): 415–423.

Mealtime insulin: Ultra-rapid
insulin lispro as a solution
Dr Hood Thabit
Disclosures

Dr Thabit

• Advisory board

– Roche Diabetes

• Research support

– Dexcom Inc

• Speaker bureaus

– Eli Lilly, Dexcom Inc

 What is URLi?
URLi is a novel, prandial insulin lispro formulation developed to more closely
match physiological prandial insulin secretion, with the goal of improving
PPG control.1 It contains the following excipients:1,2

Citrate

• Speeds insulin absorption by enhancing local vascular permeability2

Treprostinil

• A prostacyclin analogue currently approved for treatment of pulmonary arterial

hypertension1
• Further enhances the absorption of insulin lispro via local vasodilation1
• Undetectable in plasma after dosing; exhibits no systemic effects3

PPG = post-prandial glucose; URLi = ultra-rapid insulin lispro.

1
Klaff L, et al. Diabetes Obes Metab. 2020;22(10): 1799–1807. 2Lyumjev [Summary of Product Characteristics]. Utrecht, Netherlands: Eli Lilly Nederland B.V. 2023. 3Linnebjerg H, et al. Clin
Pharmacokinet. 2020;59(12): 1589–1599.
 Insulin subcutaneous absorption1–4
Insulin lispro vs rapid lispro
Hexamers Monomers

Insulin lispro
Dissociation/diffusion

Capillary endothelium

URLi Dissociation/diffusion
Increased permeability
Citrate, treprostinil

Capillary endothelium

Vessel
dilation

URLi = ultra-rapid insulin lispro.

1
Modified according to Hirsch IB, et al. Endocr Rev. 2020;41(5): 733–755. 2Bakaysa DL, et al. Protein Sci. 1996;5(12): 2521–2531. 3Pechenov S, et al. Adv Drug Deliv Rev. 2017;112: 106–
122. 4Leohr J, et al. Clinical Pharmacokinetics. 2020;59(12): 1601–1610.
 URLi has faster absorption and initial action than insulin lispro
T1DM
First hour after injection 8 First 2 hours after injection
600

Mean glucose infusion

concentration (pmol/L)
Serum insulin lispro

rate (mg/kg/min)
500
600 8 6
400

Mean glucose infusion rate

500 300 4
concentration (pmol/L)
Serum insulin lispro

200 6
2
400

(mg/kg/min)
100

0 0
300 4 0 1 2
0.0 0.2 0.4 0.6 0.8 1.0

Time after injection (h) Time after injection (h)

200
2
100

0 0
0 2 4 6 8 0 2 4 6 8

Time after injection (h) Time after injection (h)

URLi had 5.6 minutes of earlier appearance in serum and a URLi had 11 minutes of faster insulin action and a
7.2-fold increase in the exposure within the first 15 minutes 2.8-fold increase in insulin action in the first 30 minutes
This was a phase I, two-period, randomised, double-blind, crossover glucose clamp study in younger adult
(aged 18-45 years; n = 41) and elderly (aged ≥ 65 years; n = 39) patients with T1DM.
T1DM = type 1 diabetes mellitus; URLi = ultra-rapid insulin lispro. URLi Lispro
Modified according to Linnebjerg H, et al. Clin Pharmacokinet. 2020;59(12): 1589–1599.
 URLi has faster absorption and initial action than insulin lispro
(cont.)
T2DM First 2 hours after injection
First hour after injection
500 5

Mean glucose infusion

concentration (pmol/L)
Serum insulin lispro

rate (mg/kg/min)
500 400 5 4

Mean glucose infusion rate

300
concentration (pmol/L)

400 4
Serum insulin lispro

2
200
1

(mg/kg/min)
100
300 3 0
0
0 1 2
0.0 0.2 0.4 0.6 0.8 1.0
200 2 Time after injection (h)
Time after injection (h)

100 1

0 0
0 2 4 6 8 10 0 2 4 6 8 10

Time after injection (h) Time after injection (h)

URLi had 5.3 minutes of earlier appearance in serum and a URLi had 13 minutes of faster insulin action and a
6.4-fold increase in the exposure within the first 15 minutes 4.2-fold increase in insulin action in the first 30 minutes
This was a phase I, randomised, two-period, two-treatment, double-blind, crossover study in 38
patients with T2DM. Data presented as mean ± standard error.
T2DM = type 2 diabetes mellitus; URLi = ultra-rapid insulin lispro. URLi Lispro
Modified according to Leohr J, et al. Clin Pharmacokinet. 2020;59(12): 1601–1610.
 URLi had a greater reduction in PPG in people with T1DM
3.5
URLi Lispro Aspart Faster aspart Healthy subjects

3.0

Change from premeal BG (mmol/L)

2.5

Improvement in PPG
2.0
excursions with URLi
was statistically 1.5

significant vs insulin
lispro and insulin 1.0

aspart 0.5

-0.5

0 1 2 3 4 5

Time after meal (h)

This was a randomised, double-blind, four-period, crossover study, conducted in 68 patients with T1DM.
URLi vs lispro: p < 0.05 to AUC (0–3 hours; 0–4 hours); p < 0.01 ∆ BG 2 hours; p < 0.001 to AUC (0–1 hour; 0–2 hours) and ∆ BG 1 hour; URLi vs aspart: p < 0.001 to AUC (0–1 hour; 0–2 hours; 0–3 hours) and
∆ BG 1 and 2 hours. Data are presented as mean + standard error.
AUC = area under the plasma concentration–time curve; BG = blood glucose; PPG = post-prandial glucose; T1DM = type 1 diabetes mellitus; URLi = ultra-rapid insulin lispro.
Modified according to Heise T, et al. Diabetes Obes Metab. 2020;22(10): 1789–1798.
 Mealtime URLi was superior to insulin lispro in controlling PPG
PRONTO-T1D
7 MMTT at week 26

6
a
PPG excursions (mmol/L)

5 a

4 b b

b
a
3 2-h ETD mealtime URLi vs lispro
-1.73 mmol/L (95% CI -2.28; -1.18)
2 b
a b 1-h ETD mealtime URLi vs lispro
1 −1.55 mmol/L (95% CI −1.96; −1.14)

a
0
0 20 60 120 180 240

Time after meal (min)

Insulin given at or 20 min
after meal start Mealtime URLi Mealtime lispro Post-meal URLi

PRONTO-T1D was a 26-week, treat-to-target, phase 3 trial of URLi vs lispro in 1222 adults with T1DM. Data are least squares mean ± standard error.
a
p < 0.05 for comparison vs insulin lispro. bp < 0.001 for comparison vs insulin lispro.
CI = confidence interval; ETD = estimated treatment difference; MMTT = mixed meal tolerance test; PPG = post-prandial glucose; T1DM = type 1 diabetes mellitus; URLi = ultra-rapid insulin lispro.
Modified according to Klaff L, et al. Diabetes Obes Metab. 2020;22(10): 1799–1807.
 URLi was superior to lispro in controlling PPG
PRONTO-T2D
MMTT at week 26

PPG Excursions (mmol/L) 5

4
b
2-h ETD URLi vs lispro b
−0.96 mmol/L (95% CI −1.41; −0.52)
3 b
1-h ETD URLi vs lispro
−0.66 mmol/L (95% CI −1.01; −0.30) a
2 a

0
0 15 30 60 120 180 240

Time (min)
URLi Lispro
PRONTO-T2D was a 26-week, treat-to-target, phase 3 trial of URLi vs lispro in 673 patients with T2DM on a basal bolus insulin regimen. Data are least squares mean ± standard error.
a
p < 0.05. bp < 0.001.
CI = confidence interval; ETD = estimated treatment difference; MMTT = mixed meal tolerance test; PPG = post-prandial glucose; T2DM = type 2 diabetes mellitus; URLi = ultra-rapid insulin lispro.
Modified according to Blevins T, et al. Diabetes Care. 2020;43(12): 2991–2998.
 Rate and incidence of hypoglycaemia
PRONTO-T1D
All documented hypoglycaemia Nocturnal hypoglycaemia

14.5 14.24 16

14
14

Events/patient/year
Events/patient/year

13.48 12
13.5
10

13 8
12.46 6
12.5
4
12 1.75
2 1.25 1.24

11.5 0
0-26 weeks 0-26 weeks

Incidence 88.2% 90.4% 90.5% 31.5% 32.8% 30.5%

Mealtime URLi Mealtime lispro Post-meal URLi

PRONTO-T1D was a 26-week, treat-to-target, phase 3 trial of URLi vs lispro in 1222 adults with T1DM. Data are least squares mean ± standard error. Hypoglycaemia was defined as <3.0 mmol/L (<54 mg/dL).
T1DM = type 1 diabetes mellitus; URLi = ultra-rapid insulin lispro.
Modified according to Klaff L, et al. Diabetes Obes Metab. 2020;22(10): 1799–1807.
 Rate of hypoglycaemia in people with T2DM
PRONTO-T2D

All documented hypoglycaemia Nocturnal hypoglycaemia

from weeks 0 to 26 from weeks 0 to 26
RR=1.02 RR=1.29
10 10
7.57 7.43
8

Events/patient/year
8
Events/patient/year

6 6

4 4

2 2
0.68 0.53
0 0

URLi Lispro

PRONTO-T2D was a 26-week, treat-to-target, phase 3 trial of URLi vs lispro in 673 patients with T2DM on a basal bolus insulin regimen. Data are least squares mean ± standard error. Hypoglycaemia was
defined as <3.0 mmol/L (<54 mg/dL). All documented hypoglycaemia = hypoglycaemia with or without symptoms; nocturnal hypoglycaemia = documented hypoglycaemia from bedtime to waking.
RR = relative risk; T2DM = type 2 diabetes mellitus; URLi = ultra-rapid insulin lispro.
Modified according to Blevins T, et al. Diabetes Care. 2020;43(12): 2991–2998.
Conclusions

• Novel ultra-rapid-acting insulins provide additional bolus insulin options, and their quick
onset of action provides additional dosing flexibility for people with diabetes

• Given the comparable efficacy and safety of these novel insulins compared with other quick-
acting insulins, healthcare providers should engage in shared decision-making with patients
and their caregivers regarding the possible use of ultra-rapid-acting insulin, considering their
preferences, individualised considerations and insurance formulary coverage

• These new insulin formulations may be a suitable option for people with diabetes not at post-
prandial glycaemic targets with other bolus insulins
 Managing blood sugar and meeting goals can be challenging in
many patients1
Antonio Cindy Joanna

• Is 16 years of age; newly diagnosed with T1D • Is 32 years of age; has had T1D for • Is 59 years of age; has had T2D for 11 years
• Recently got a flash glucose meter 3 years • On basal insulin, an OAM and a GLP-1 RA
• Calculates her insulin dose and injects at
• Is generally managing well but is frustrated • Postprandial readings are frequently high (>11.1
mealtime when eating out
that his PPG is regularly too high mmol/L) (>200 mg/dL)
• Is afraid of nighttime hypoglycaemia so usually
• Wants to manage his PPG better to maximise • Her busy lifestyle results in unpredictable meal
rounds down the insulin dose at dinner
his TIR sizes and timing
• Has a BG measurement of
• She wants a sense of normalcy in her daily life
10.5 mmol/L (190 mg/dL) before going to bed
and social interactions
• Despite trying her best, is not achieving her
HbA1c goals but is willing to work with her
*All patient data are anonymous and presented in a hypothetical scenario for illustration purposes only. physician to have a better control of her blood
BG = blood glucose; GLP-1 RA = glucagon-like peptide-1 receptor agonist; HbA1c = glycated haemoglobin; OAM = oral antihyperglycaemic medication; PPG = sugar
postprandial glucose; T1D = type 1 diabetes; T2D = type 2 diabetes; TIR = time in range.
1
American Diabetes Association – Standards of Medical Care in Diabetes. Diabetes Care. 2020;43(suppl 1): S34–S47.
 Let us look at some
practical case
scenarios with
mealtime insulin
⮚ T2DM on mealtime insulin – Christophe De Block
⮚ T1DM on mealtime insulin – Hood Thabit
⮚ T1DM on pump – Hood Thabit

T1DM = type 1 diabetes; T2DM = type 2 diabetes mellitus.

 A T2DM patient on mealtime insulin
Prof Christophe De Block

T2DM = type 2 diabetes mellitus.

 Male: 62 years of age

Nicotine: never
Patient history

✔ Diagnosed with diabetes at age 45 years;

beta cell-autoantibodies negative, no Alcohol: 5 units/week
ketosis
✔ Angina pectoris (04/2012):
Coronary angiography: normal LV
function, 50% stenosis mid LAD Cycles 2 x 50 km/week
(FFR 0.86), 40% occlusion distal RCA
– 02/2015: PCI mid-LAD
✔ Hypertension Football referee for youth
✔ Hypercholesterolemia team at the weekends

*All patient data are anonymous and presented in a hypothetical scenario for illustration purposes only.
FFR = fractional flow reserve; LAD = left anterior descending artery; LV = left ventricular; PCI = percutaneous coronary intervention; RCA = right coronary artery.
 Male: 62 years of age
Physical exam

Medication
BP 132/76 mmHg
Diabetes

1.72 m
Metformin 850 mg twice daily

Canagliflozin 300 mg once daily

Insulin aspart 8 + 9 + 12 U/day

Antihypertensive agents Insulin glargine 20 U

Perindopril 10 mg once
daily BMI
Sotalol 160 mg per day Lipid-lowering agents
Rosuvastatin 40 mg per day 28.7 kg/m2
Other agents
Molsidomine 16 mg once daily
Aspirin 80 mg once daily

*All patient data are anonymous and presented in a hypothetical scenario for illustration purposes only.
BMI = body mass index; BP = blood pressure: U = units.
85 kg
 Male: 62 years of age Food intake

Breakfast:
3 slices of bread with chocolate

Diabetes clinical status (01 Dec 2022)

Lunch:
✔ Feels good 6 slices of bread with ham/cheese/…or
✔ Changes insulin needles on daily basis, rotates charcuterie
his injection sites, well educated
✔ No hypoglycaemia unawareness, but FEAR of
hypos
Dinner:
– Prefers to go to sleep with glucose levels Hot meal with 3 potatoes, lots of
around 200 mg/dL (~11 mmol/L) due to fear vegetables and 100 g of meat/fish/chicken
of nocturnal hypoglycaemia
– Only starts giving correction boluses of
insulin at >250 mg/dL (~14 mmol/L)
✔ Sometimes forgets to inject prior to meals Pre-bedtime:
Waffle (does not
bolus for this)

*All patient data are anonymous and presented in a hypothetical scenario for illustration purposes only.
 Patient’s glucose profile
GLUCOSE STATISTICS AND TARGETS TIME IN RANGES

18 November 2020 - 1 December 2020 14 Days

% Time Sensor is Active 96%

Ranges And Targets For Type 1 or Type 2 Diabetes

Very High
>250 mg/dL
13%
(3h 7min) • Insulin aspart: 8 + 9 + 12 U;
Glucose Ranges
Target Range 3.9-10.0 mmol/L
Targets % of Readings (Time/Day)
Greater than 70% (16h 48 min) High 23%
insulin glargine: 22 U
181 - 250 mg/dL (5h 31min)
Below 70 mg/dL Less than 4% (58min)
Below 54 mg/dL Less than 1% (14min)
Above 180 mg/dL Less than 25% (6h) Target Range 62%

• GMI: 7.3% (56 mmol/mol)

Above 250 mg/dL Less than 5% (1h 12min) 70 - 180 mg/dL (14h 53min)
Each 5% increase in time in range (70-180 mg/dL) is clinically beneficial.

Average Glucose 168 mg/dL Low 2%

• TIR: 62%
54 - 69 mg/dL (29min)
Glucose Management Indicator (GMI) 7.3% of 56 mmol/mol
Glucose Variability 40.7% Very Low 0%
<54 mg/dL (0min)
Defined as percent coefficient of variation (%CV); target ≤36%
• TBR: 2%
AMBULATORY GLUCOSE PROFILE (AGP)
AGP is a summary of glucose values from the report period, with median (50%) and other percentiles shown as if occurring in a single day
• CV: 40.7%
• Mean glucose: 168 mg/dL (9.3 mmol/L)

Target Range

*All patient data are anonymous and presented in a hypothetical scenario for illustration purposes only.
CV = coefficients of variation; GMI = glucose management indicator; TBR = time below range; TIR – time in range.
 Patient’s glucose monitoring results
Thursday 19 Nov

Glucose mg/dL

Carbs Grams
Rapid-acting insulin 8.0
Units
12.0
Units
• Insulin aspart: 8 + 9 + 12 U;
Long-acting insulin 20.0
Units insulin glargine: 22 U
Friday 20 Nov

Glucose mg/dL
• High post-breakfast
• High post-lunch
Carbs Grams
Rapid-acting insulin 8.0
Units
9.0
Units
10.0
Units
• High post-dinner
Long-acting insulin 20.0
Units

Saturday 21 Nov
• No correction boluses

Glucose mg/dL

Carbs Grams
8.0 10.0 10.0
Rapid-acting insulin Units Units Units

Long-acting insulin 20.0

Units

*All patient data are anonymous and presented in a hypothetical scenario for illustration purposes only.
Carbs = carbohydrates; U = units.
 Patient’s core problems

• Fear of hypos, afraid to use correction boluses

• High postprandial values
• Sometimes forgets to inject preprandially

• Switch to ultra-rapid insulin lispro

*All patient data are anonymous and presented in a hypothetical scenario for illustration purposes only.
 Patient’s glucose profile after switch to ultra-rapid insulin lispro
GLUCOSE STATISTICS AND TARGETS TIME IN RANGES

7 February 2023 - 20 February 2023 14 Days

% Time Sensor is Active 94%
Very High 6%
>250 mg/dL (1h 26min)
Ranges And Targets For Type 1 or Type 2 Diabetes

Glucose Ranges Targets % of Readings (Time/Day) 26%

High
Target Range 3.9-10.0 mmol/L
Below 70 mg/dL
Greater than 70% (16h 48 min)
Less than 4% (58min)
181 - 250 mg/dL (6h 14min)
• Ultra-rapid insulin lispro: 9 + 9 + 12 U;
Below 54 mg/dL
Above 180 mg/dL
Less than 1% (14min)
Less than 25% (6h)
insulin glargine 22 U
Target Range 68%
Above 250 mg/dL Less than 5% (1h 12min) 70 - 180 mg/dL (16h 20min)
Each 5% increase in time in range (70-180 mg/dL) is clinically beneficial.

Average Glucose 162 mg/dL Low 0%

Glucose Management Indicator (GMI) 7.2% of 55 mmol/mol
54 - 69 mg/dL

Very Low
(0min)

0%
• GMI: 7.2% (56 mmol/mol)
Glucose Variability 33.7%
<54 mg/dL (0min)

• TIR: 68%
Defined as percent coefficient of variation (%CV)

AMBULATORY GLUCOSE PROFILE (AGP)

AGP is a summary of glucose values from the report period, with median (50%) and other percentiles shown as if occurring in a single day • TBR: 0%
• CV: 33.7%
• Mean glucose: 162 mg/dL (9.0 mmol/L)

Target Range

*All patient data are anonymous and presented in a hypothetical scenario for illustration purposes only.
CV = coefficients of variation; GMI = glucose management indicator; TBR = time below range; TIR – time in range.
 Conclusions

• GMI and mean glucose remained stable

• TIR and TBR improved
• CV improved

• Patient more confident, less fear of hypos

• More flexibility (timing of injections)

*All patient data are anonymous and presented in a hypothetical scenario for illustration purposes only.
CV = coefficients of variation; GMI = glucose management indicator; TBR = time below range; TIR – time in range.
 A T1DM patient on mealtime insulin
Dr Hood Thabit

T1DM = type 1 diabetes.

 Male: 32 years of age

• 32 year-old male
• T1DM for 15 years
• Attended DAFNE 2014
• RA insulin: insulin aspart (carb counts)
• Basal insulin: insulin degludec 20 units PM

• Frustrated with current injection timing

• Post-prandial excursions in spite of
premeal injections
• Drives for a living, concerned with post-
prandial hypos and increasing prandial
dose

*All patient data are anonymous and presented in a hypothetical scenario for illustration purposes only.
DAFNE = Dose Adjustment for Normal Eating; RA = rapid-acting; T1DM = type 1 diabetes.
 Daily glucose profile before ultra-rapid insulin lispro

*All patient data are anonymous and presented in a hypothetical scenario for illustration purposes only.
CGM = continuous glucose monitoring.
 Follow-up 3/12 months later

• Ultra-rapid insulin lispro started Jan

2021

• Same mealtime doses as previous

• TIR increased from 68% to 82%
• Lower PPG with less perceived hypos

• Patient feels better and more confident

in adjusting meal-time doses

*All patient data are anonymous and presented in a hypothetical scenario for illustration purposes only.
PPG = postprandial glucose; TIR – time in range.
 Daily glucose profile after ultra-rapid insulin lispro

*All patient data are anonymous and presented in a hypothetical scenario for illustration purposes only.
CGM = continuous glucose monitoring.
 A T1DM patient on pump
Dr Hood Thabit

T1DM = type 1 diabetes.

 Female: 57 years of age

• 57 year-old female
• T1DM for 16 years
• DAFNE graduate
• On insulin pump since 2014
• Omnipod and FreeStyle Libre 2

• Has her own business, works

long hours and always busy
• Finds it challenging to bolus 15
mins before eating consistently
• Postprandial hyperglycaemia and
delayed hypoglycaemia

• Started ultra-rapid insulin lispro

March 2021

*All patient data are anonymous and presented in a hypothetical scenario for illustration purposes only.
DAFNE = Dose Adjustment for Normal Eating; T1DM = type 1 diabetes.
 Daily glucose profile pre- and post- ultra-rapid insulin lispro

Pre-ultra-rapid insulin lispro Post-ultra-rapid insulin lispro

*All patient data are anonymous and presented in a hypothetical scenario for illustration purposes only.
Carbs = carbohydrates.
 Post-ultra-rapid insulin lispro

*All patient data are anonymous and presented in a hypothetical scenario for illustration purposes only.
AGP = ambulatory glucose profile.
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