Use of insulin in diabetes mellitus

1. By: Geeta
M.Pharm (Ist year)
Pharmacy practice department
Use Of Insulin In Diabetes Mellitus
(DM)

2. Insulin and diabetes mellitus
 Acc. To WHO, “Diabetes is a chronic disease that occurs
either when the pancreas does not produce enough insulin
or when the body cannot effectively use the insulin it
produces.”
 1/12 person is suffering from diabetes and 1/2 diabetic
individual do not know that he is suffering from diabetes
 Insulin is a pancreatic enzyme responsible maintaing the
blood glucose levels
2 References:
1.Diabetes Fact sheet N°312. 2015 jan. Available from: http://www.who.int/mediacentre/factsheets/fs312/en

3. Hypoglycemic action of insulin
Liver
Adipose
tissuesMuscles
•Inhibits gluconeogenesis and
glycogenolysis
•Stimulates glycolysis
•Inhibits flow to
gluconeogenesis precursors to
liver
•Stimulates glucose uptake
•Inhibit gluconeogenesis and also
inhibits the flow of gluconeogenesis
precursors to the liver
•Stimulates glucose uptake
3 References :
1.Davis NS. Goodman & Gilman’s The pharmacological basis of therapeutics. 11th ed:1619-1645

4. Classification of insulin preparations
• Prepared via DNA recombinant
technology and is structurally similar
to human insulin
• Lesser mitogenicity and better efficacy
Human
• Derived from beef (bovine) or pork
(porcine)
• Risk of mitogenicity is higherAnimal
4
References:
1. Richter B, Neises G. Human insulin versus animal insulin in people with diabetes mellitus. The Cochrane
Library 2005;1:1-73

5. Pharmacokinetic classification
Category of
insulin
Type of insulin
(brand name)
Onset Peak Action
Rapid acting Lispro(humolog) 15-30 min. 30-90 min 3-5 h
Aspart (novolog) 10-20 min. 40-50 min. 3-5 h
Glulisine (apidra) 20-30 min. 30-90 min. 1-2½ h
Short acting Regular (humulin or
novolin) 30 min. -1 h 2-5 h 5-8 h
Velosulin ( used in
insulin pump) 30 min.-1 h 2-3 h 2-3 h
Intermediate
acting
NPH (N)
1-2 h 4-12 h 18-24 h
Long acting Insulin glargine
(lantus)
1-1½ h steady level 20-24 h
Insulin detemir
(levemir)
1-2 h 6-8 h Up to 24 h
5

6. Premixed insulin
Humulin 70/30 30 min. 2-4 h 14-24 h
Novolin 70/30 30 min. 2-12 h Up to 24 h
Novolog 70/30 10-20 min. 1-4 h Up to 24 h
Humulin 50/50 30 min. 2-5 h 18-24 h
Humalog mix 75/25 15 min. 30 min.-2½ h 16-20 h
Strength of insulin: U-100, which means it has 100 units of
insulin per milliliter of fluid, though U-500 insulin is available for
patients who are extremely insulin resistant.
6 References:
1.Types of insulin. Available from: http://www.webmd.com/diabetes/guide/diabetes-types-insulin/

7. Clinical safety and efficacy of insulin analogues
Treat to target study compared of insulin glargine and NPH
glargine reduces hypoglycaemias. Insulin detemir showed
similar results when added as basal insulin for type 2 diabetic
patients
INSIGHT study compared OAD thearapy and OAD + insulin
early initiation of insulin Glargine improves glycaemic control
and is more effective as compared to OAD alone
7
References :
1.Riddle MC, Rosenstock J, Gerich J. The treattotarget trial: randomized addition of glargine or human NPH
insulin to oral therapy of type 2 diabetic patients. Diabetes Care. 2003;26(11):3080–3086.
2.Gerstein HC, Yale JF, Harris SB, Issa M, Stewart JA, Dempsey E. A randomized trial of adding insulin
glargine vs. avoidance of insulin in people with Type 2 diabetes on either no oral glucose lowering agents or
submaximal doses of metformin and/or sulphonylureas. The Canadian INSIGHT (implementing new strategies
with Insulin glargine for hyperglycaemia treatment) Study. Diabetic Medicine. 2006;23(7):736–742.

8. Insulin therapy for non pregnant adults
Glycemic targets
A1C levels < 7%
Preprandial capillary plasma
glucose
80-130 mg/dL
Peak postprandial capillary
plasma glucose
<180mg/dL
8
Diet/
exercise
Oral
monotherapy
Oral
combination
Insulin
Oral
+/- insulin
Contd…

9. • Basal insulin
• Start at: 10 U/day or 0.1-0.2 U/kg/day
• Usually with metformin ± other noninsulin agent
Insulin therapy
• Add1 rapid acting insulin injection before largest meal
• Start at: 4U or 0.1 U/kg or 10% of basal dose
If not controlled
• Changed to premixed insulin twice daily
• Start at: Divide current basal dose into 2/3 AM, 1/3 AM or 1/2 AM ,
1/2 PM
If not controlled
• Add ≥2 rapid insulin bolus injections before meal (basal – bolus)
• Start at: 4U or 0.1 U/kg or 10% of basal dose/meal
If not controlled
9
References:
1.Standards of Medical Care in Diabetes. January 2015 Volume 38, Supplement 1. J Diabetes care.s41-s48
2.IDF Treatment Algorithm for People with Type 2 Diabetes. Available from:
httpp://www.idf.org/sites/default/files/Type%202%20treatment%20algorithm.pdf

10. Insulin therapy for gestational diabetes
Glycemic targets
Preprandial
and either
≤ 95 mg/dL
One-hour postmeal ≤ 140 mg/dL
Two-hour postmeal ≤ 120 mg/dL
For pregnant women having preexisting type 1 DM or type
2 DM the glycemic goals include:
• Premeal, bedtime, and overnight glucose 60–99
mg/dL (3.3– 5.4 mmol/L)
• Peak postprandial glucose 100–129 mg/dL (5.4–
7.1 mmol/L)
• HbA1C ,6.0%
10
Contd…

11. Insulin intake during pregnancy
Weeks Daily insulin dose
1-18 0.7 U/kg actual body weight
18-26 0.8U/kg actual body weight
26-36 0.9U/kg actual body weight
36-40 1.0U/kg actual body weight
11
References:
1. Standards of Medical Care in Diabetes. January 2015 Volume 38, Supplement 1. J Diabetes care.s77-s79
2. Catalano PM. Trying to understand gestational diabetes. Diabetes Med.2014 Mar;31(3):273-281
3. Thomas A. Buchanan and Anny H. Xiang. Gestational diabetes mellitus .J Clin Invest. 2005 Mar 1; 115(3):
485–491.

12. Insulin therapy for children and adolescence
Glycemic targets
Age (years)
Plasma blood glucose range
(mg/dl)
HbA1C
range
Before meal Bedtime
0-6 100-180 110-200 7.5-8.5
6-12 90-180 100-180 <8%
13-19 90-130 90-150 <8%
Insulin sensitivity related to sexual maturity, physical
growth, ability to provide self-care and unique neurologic
vulnerability to hyperglycemia are the factors that make
children a special population
12
Contd …

13. Insulin therapy recommendations
Age (years) Dose Drug
< 5 0.1 U/kg Regular insulin/ NPH
≥ 5 0.2 U/kg Regular insulin/NPH
13
References:
1. Standards of Medical Care in Diabetes. January 2015 Volume 38, Supplement 1. J Diabetes care.s70-s73
2. Global IDF/ISPAD Guideline for diabetes in childhood and adolescence. 21-28

14. Insulin therapy for elderly
Glycemic targets
Patient
characteristics/
health status
Reasonable
A1C goal
Fasting or pre-
prandial
glucose
(mg/dL)
Bedtime
glucose
(mg/dL)
Blood pressure
(mmHg) Lipids
Healthy 7.5% 90–130 90–150 140/90
Complex/inter
mediate
8.0% 90–150 100–180 140/90
Very complex/
poor health
8.5% 100–180 110–200 150/90
 Therapy is initiated with a relatively low dose and titrated until the goal is
achieved
 Individualized therapy & lifestyle modification
14
Contd…

15. Insulin therapy recommendation
Level of therapy Drug of choice Ist Alternative 2nd alternative
1st line Metformin
Sulphonyl ureas or
DPP-4 inhibitor
Acarbose or
Glinides or
Insulin or
SGLT2 inhibitors or
thiozolidions
2nd line
Sulphonyl ureas or
DPP-4 inhibitor
Metformin ( if not
used in 1st line
therapy)
Acarbose or
Glinides or
Insulin or
SGLT2 inhibitors or
thiozolidions
3rd line
Sulphonyl ureas or
DPP-4 inhibitor +
basal insulin or
premixed insulin
GLP1-RA
Acarbose or
Glinides or
Insulin or
SGLT2 inhibitors or
thiozolidions
4th line
Change oral agent or basal insulin or pre-mixed insulin or GLP1-
RA or basal + meal time insulin
15
References :
1. Standards of Medical Care in Diabetes. January 2015 Volume 38, Supplement 1. J Diabetes care.s67-s69
2. Blood glucose treatment algorithm for older people with diabetes recommended by IDA. Available from:
https://www.idf.org/sites/default/files/IDF-Guideline-for-older-people-T2D.pdf

16. Types of insulin therapies
1. Multiple daily injection (MDI)
2. Continuous subcutaneous insulin infusion therapy (CSII)
3. Continuous subcutaneous glucose monitoring (CGM)
4. Artificial closed loop system- artificial pancreas
 Extracorporeal subcutaneous system
 Implantable intraveneous-intraperitoneal system
16
References:
1.Valla V. Therapeutics of Diabetes Mellitus: Focus on Insulin Analogues and Insulin Pumps. Exp Diabetes
Res. 2010;1-10

17. Insulin injecting devices
Needle and syringe
• Angle and site of injection are the major factors
• Painful and risky procedure
Insulin pens
• Looks like a pen with a cartage with insulin
• Convenient, easy to use and less painful
Injection pump
• Consists of an insulin reservoir with needle &plunger
• Allows the release of insulin dose in a continuous fashion
17

18. Injection ports
• Consists of a canula inserted into the tissue beneath the skin
• It reduces the number of skin punchers
Insulin aids
• consists of a button for injecting the insulin
• makes the insulin administration easy
Insulin jet injector
• It sends a fine spray of insulin into the skin at high pressure
• Insulin is absorbed through the skin and also the need of
injection is eliminated
18
References:
1.Valla V. Therapeutics of Diabetes Mellitus: Focus on Insulin Analogues and Insulin Pumps. Exp Diabetes Res.
2010;1-10
2.Insulin injecting devices. Available from: www.niddk.nih.gov/health-information/health

19. Cost of insulin therapy
References:
1.Orlo I & diatribe team. Unpacking the rising cost of insulin and what it means for patients.2015 nov:1-3.
19
 Cost of insulin analogue =3-8 (cost of regular/ NPH insulin)

20. Key points for using insulin therapy
 Self monitoring of blood glucose
 Educate patient: injection technique, diet regulation, and
prevention and treatment of hypoglycemia.
 Tailoring the insulin regimen
 Use of enough insulin
20

21. Side effects
21 Reference:
1. Insulin side effects. Available from: www.drugs.com/sfx/insulin-side-effects.html
InsulinHypoglyce
mia
Occular
disturbance
s
Hypersensi
tivity
Increased
risk of
CVD
Weight
gain
Hypophosp
hatemia
Renal
insufficienc
y
Increased
Willebrand
factor

22. Current recommendation for insulin
 The therapy needs to be modified according to patient
variability and its health status
 Initial insulin regimen including basal insulin injection
once daily if HbA1C levels are not controlled
 Early initiation of insulin therapy for reduction in
cardiovascular disease in diabetic population
 Insulin + OHAs combination for better glycemic control
and improved QOL
22
References:
ADA and EASD recommendations
IDF recommendations

23. Recent advances in insulin therapy

24. Upcoming tools for insulin administration
Reference:
1. Treatment of diabetes. Available from: www.diabetes.co.uk/24
 Insulin inhalers: use compressed air to deliver a dose of
dry insulin or dissolved rapid-acting insulin that can then
be inhaled
 Artificial pancreas: manmade device which mimics the
role of pancreas
 Encapsulated islet cells: stem cell capable of growing to
a new insulin producing cell encapsulated in a protective
covering
 Diabetes vaccine: act by stopping or preventing the T-
cells attacking the body’s own cells
 Diamyd vaccine trial
 Nanoparticle vaccine

25. Short term intensive insulin therapy (SIIT)
 Glycemic remission after 2-3 week therapy
 Strategy for modifying natural history of disease
 Improved β-cell function and reduced insulin resistance in
newly diagnosed patients
Risks involved:
 ACCORD study showed remission of glycemic control in
type 2 DM, caused increase in mortality, including deaths
from CVDs
 Also the use of SIIT can led to insulin mediated metabolic
stress and this may result in metabolic cardiomyopathy (in
heart) and metabolic myopathy (in skeletal muscles)
25
References:
1. Kramer CK, Zinman B, Retnakaran R. Short-term intensive insulin therapy in type 2 diabetes
mellitus:systematic review and meta-analysis. Lancet Diabetes Endocrinol 2013; 1:28–34

26. Insulin monotherapy v/s combination therapy
A review article published in The Cochrane Library 2004,Issue
4,showed the following results:
 OHA therapy with a single bedtime injection of NPH insulin
show no difference in benefits only the therapy with insulin-
metformin shows significant benefits on glycemic controls.
 Combination therapy reduces total daily insulin
requirement of 46% compared to insulin monotherapy
 Combination therapy lesser weight gain
26
References :
1.Goudswaard AN, Furlong NJ, Valk GD, Stolk RP, Rutten GEHM. Insulin monotherapy versus
combinations of insulin with oral hypoglycaemic agents in patients with type 2 diabetes mellitus. he
Cochrane Library 2004;4:1-63

27. Automated insulin in the critically ill patients
 Software guided intensive insulin therapy ( SG-IIT)
tighter, faster, and less variable, with less hypoglycemia
compared with paper-based IIT protocols
 Software algorithms are divided into three groups:
1. Heuristic protocol: the paper based protocol is converted
into software
2. Leuven protocol: safe and easy as the paper protocol but
does not take glucose variability in account.
3. Proportional integrated derivative (PID) models: uses
previous blood glucose values to titrate insulin
administration.
27 Contd...

28. Commercially Available Software-Guided Intensive Insulin Therapy
Name Descripti
on
Comments
EndoTool PID Can be potentially interfaced with existing electronic
medical records.
Poor data: one article looking only at glucose level.
GlucoCare PID Can choose from multiple well-studied protocols,
including customizable ones.
Glucommander PID Also approved in pediatric populations.
Studied in several adult intensive care unit populations.
GlucoStabilizer PID Studied in intensive care unit and non-intensive care unit
populations.
GRIP PID Available for free download.
Few studies.
Space
GlucoseControl
MPC Built into proprietary insulin pumps.
Well studied.
28
References:
1.Rattan R, Nasraway SA. The Future Is Now: Software-Guided Intensive Insulin Therapy in the Critically Ill.
J Diabetes Sci Technol . 2013;7(2):549-551

29. Future aspects
29
Instead of choosing insulin as a end stage treatment early initiation
of insulin therapy should be done.
Areas yet to discover:
 Standards for use of insulin in special condition
 Crieteria for selecting proper insulin analogue during treatment
 Formal training for physician and patients regarding safe and
rational use of medication
During the next few years, we will likely see the introduction of
more new basal and prandial insulin analogs, including different
preparations of pulmonary inhaled insulin.

30. 30