3. HLG/CYCLEJAN2017/22
Company Confidential
@ 2016 Eli Lilly and Company
Objective
3
Understand the
patient profile for
initiation with
Lispro Mix 25 and
validate its
efficacy, safety
and durability
Evaluate options
available for
insulin initiation
by reviewing a
hypothetical case
Discuss the
present insulin
initiation scenario
in Type 2 diabetes
in India
1 2 3
5. HLG/CYCLEJAN2017/22
Company Confidential
@ 2016 Eli Lilly and Company
In present scenario insulin initiation is already
delayed
Failure to advance therapy
when recommended may delay
insulin therapy by up to 8 years
Diabetes, Obesity and Metabolism, 10 (Suppl. 2), 2008, 5–13
In India, insulin therapy is initiated only when the HbA1c levels have
deteriorated to around 9%
6. HLG/CYCLEJAN2017/22
Company Confidential
@ 2016 Eli Lilly and Company
Basis local needs, commonly utilized insulin regimens are
different around the world1
NPH = neutral protamine Hagedorn.
IDF Global Guideline for Type 2 Diabetes. Begin with a basal insulin once daily such as NPH insulin, insulin glargine, or insulin detemir.2
1. Polinski JM, et al. BMC Endocr Disord. 2015;15(46):1-9. 2. International Diabetes Federation. Clinical Guidelines Task Force. 2012.
Patients(%)
Basal insulin only
100
90
80
70
60
50
40
30
20
10
0
Mixed insulin only Other insulin combinations
Premix is the most common used therapy for India
7. HLG/CYCLEJAN2017/22
Company Confidential
@ 2016 Eli Lilly and Company
Mrs. Jain, a 56-year-old female presents to her primary
care provider for her 3-month routine diabetes follow-up
Diagnosed with
T2DM ~10years
ago & initiated
on Metformin
5 years later
addition of
Glimepiride
2 years ago,
Sitagliptin due to
rising A1C and
elevated PPG level
Has difficulty
attaining
glycemic
control post
3-4 months
8. HLG/CYCLEJAN2017/22
Company Confidential
@ 2016 Eli Lilly and Company
Clinical Signs & Lab Results
Note: Hypothetical patient case
Test Parameter Result
BMI 26 kg/m2
BP 110 / 75 mm Hg
A1C 9.7%
FPG 188 mg/dL
PPG 292 mg/dL
Creatinine 0.8 mg/dL
GFR ≥ 60 mL/min
BUN 16 mg/dL
Total cholesterol 159 mg/dL
HDL 58 mg/dL
LDL 84 mg/dL
Triglycerides 84 mg/dL
Urine protein Creatinine < 30 mg/g
9. HLG/CYCLEJAN2017/22
Company Confidential
@ 2016 Eli Lilly and Company
Which of the following options would you recommend
for Mrs. Jain to get to the required targets?
1. Increase dose of Glimepiride
2. Initiate other non insulin agents
3. Initiate insulin therapy
4. Re-iterate Lifestyle Modifications; no
change in medication
10. HLG/CYCLEJAN2017/22
Company Confidential
@ 2016 Eli Lilly and Company
Consider the unique characteristics of T2DM in Asian
populations when managing your patients
Average BMI1-4
β-cell dysfunction5
High PPG excursion6
BMI = body mass index; PPG = postprandial glucose.
1. Tsai S, et al. J Diabetes. 2011;3(3):208-216. 2. Kim S, et al. Acta Diabetol. 2014;51(4):655-661. 3. Monami M, et al. J Endocrinol Invest. 2006;29(7):619-624. 4. Freemantle N, et al. Diabetes
Obes Metab. 2012;14(10):901-909. 5. Møller JB, et al. J Clin Endocrinol Metab, 2014;99(11):4273-4280. 6. Venn BJ, et al. Diabet Med. 2010;27(10):1205-1208. 7. ChartsBin statistics collector
team 2011, chartsbin.com/view/1154. Accessed 7 July 2015.
High carbohydrate diet7
11. HLG/CYCLEJAN2017/22
Company Confidential
@ 2016 Eli Lilly and Company
Present HbA1c is 9.7%. Now which anti-diabetic
class would help achieve target of <7%
ADA 2017 : Efficacy of available anti-diabetic agents
Insulin is the most potent; delivering the
highest reduction of HbA1c
12. HLG/CYCLEJAN2017/22
Company Confidential
@ 2016 Eli Lilly and Company
Now we know insulin is the best choice to get to
target values; but which insulin would you consider?
1. Basal insulin
2. Premix insulin
3. Basal plus regimen
4. Co-formulation Test Parameter Result
A1C 9.7%
FPG 188 mg/dL
PPG 292 mg/dL
13. HLG/CYCLEJAN2017/22
Company Confidential
@ 2016 Eli Lilly and Company
Contribution of PPG excursions & FBS to HbA1c levels in
Asian T2D patients using CGMS
Diabetes Metab Res Rev 2011; 27: 79–84
Significant contribuation from PPG even at
higher HbA1c levels and lesser FPG contribution
as compared to Caucasians
Similar contribution of PPG at lower HbA1c
levels as compared to Caucasians
ASIA
14. HLG/CYCLEJAN2017/22
Company Confidential
@ 2016 Eli Lilly and Company
Effect of Various Insulin Regimen in T2DM patients with
Secondary OHA failure
Untreated Basal Only Pre-mix or Basal
Bolus
Volume 23, Number 2, 2005, Clinical Diabetes
PPG excursion not normalized
14
15. HLG/CYCLEJAN2017/22
Company Confidential
@ 2016 Eli Lilly and Company
Premix Twice-daily Insulin Lispro Mix 25
Lispro Mix 25
Insulineffect
Lispro Mix 25
Meals
Roach P and Woodworth JR. Clin Pharmacokinet. 2002; 41: 1043-1057.
16. HLG/CYCLEJAN2017/22
Company Confidential
@ 2016 Eli Lilly and Company
Starting with Premix Insulin
Pros
• Simple start with single
injection with continuation of
SUs
• Effective HbA1c control
• Control of both PPG and FPG
• Option to intensify with same
insulin
Cons
• Slightly more chance of
daytime hypo (nocturnal
similar)
• Somewhat more weight gain
(not a concern in lean diabetics
and people who have los
weight due to hyperglycemia)
18. HLG/CYCLEJAN2017/22
Company Confidential
@ 2016 Eli Lilly and Company
Insulin Lispro Mix 25 vs. Glargine + Lispro: LS Mean
Change in HbA1c from Baseline to Endpoint
Bowering K et al. Diabet Med. 2012;29:e263-72.
Percent of patients reaching HbA1c target
Glargine + Lispro
(n = 184)
Insulin lispro mix 25
(n = 177)
Target HbA1c <7.0%, n (%) 70 (39.1) 68 (40.0)
Target HbA1c ≤6.5%, n (%) 34 (19.0) 36 (21.2)
p=ns
19. HLG/CYCLEJAN2017/22
Company Confidential
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Insulin Lispro Mix 25 vs. Glargine + Lispro:
Key Findings and Conclusions
Both regimens successfully lowered HbA1c from baseline to
endpoint; insulin lispro mix 25 therapy was found to be non-inferior
to glargine + lispro therapy by study end (upper limit of 95% CI <0.4)
No statistically significant differences between treatment
groups in:
– Percentage of patients achieving HbA1c targets
– Postprandial blood glucose levels
– Increase in insulin dose and weight gain
– Number of injections
– Rates of hypoglycemic events
Bowering K et al. Diabet Med. 2012;29:e263-72.
20. HLG/CYCLEJAN2017/22
Company Confidential
@ 2016 Eli Lilly and Company
DURABLE Initiation Phase – Insulin Glargine
Vs. Insulin LM25: HbA1c Change over 24 Weeks
Change in HbA1c from
baseline to initiation endpoint
-0.8
-2
-1.6
-1.2
-0.4
0
ChangeinHbA1catendpoint(%)
Insulin lispro
Mix 25
n=962
Insulin
glargine
n=977
-1.8
-1.7
p<0.01
Buse JB et al. Diabetes Care. 2009; 32(6): 1007-1013.
Buse JB et al. Diabetes Care. 2011; 34(2): 249-255.
p=0.00650
40
30
20
0
%patientsmaintainingHbA1c≤7% 10
N=202 N=147
Lispro Mix25/75 Glargine
*16.8
months
*14.4
months
* Median time of maintaining the HbA1c goal
Greater Durability of LM25 over Glargine
21. HLG/CYCLEJAN2017/22
Company Confidential
@ 2016 Eli Lilly and Company
Key Messages
Insulin initiation in India is often delayed
Basal Insulin is commonly not enough for patients to reach their HbA1c Goal
Most patients with T2D like Mrs. Jain in India have both raised fasting and
post prandial glucose levels at insulin initiation
PPG control and early mealtime insulin treatment is more important for the
management of T2DM in such patients
Lispro Mix25 offers effective glycemic control with coverage of both FPG
and PPG
Lispro Mix25 can be started once daily in select groups of patients and can
be intensified with the same insulin to twice or thrice daily depending on
the patient’s needs
