Insulin therapy in T2DM

Dr.T.V.Narayan Rao M.D.

Andhra Hospitals
drtummala@gmail.com
 “Insulin is the oldest of the
hypoglycemic agents, it is also the
only one that occurs naturally in
humans and has no upper dose limit”

Prof. David Nathan

Nejm (2002)17:1342 - 49

2
 "No single event in the history of medicine had
changed the lives of so many people, so suddenly.“

-Stephen Hume, Biographer of Banting

 Leonard Thompson (1908–1935)
Toronto, Ontario, January 11, 1922
 Novo Nordisk®

The Fantastic 4 of Insulin Discovery

MOST
CHERISHED
MOMENT

FG Banting CH Best JB Collip JJR Macleod

 UKPDS: Each single % reduction in HbA1c gives …
Every Single % point matters

Epidemiological extrapolationUKPDS,
showing benefit
Strattonof aet1%
al.reduction in mean HbA1c at 12 yrs
BMJ 2000;321;405-12
 Insulin Delivers Superior Glucose Reductions
Versus Other Agents
Oral Anti diabetic Agents

Example: Metformin SUs TZDs Exenatide Insulin

9.5% HbA1c

-0.9% -0.8%
-1.4%
-2.0%
Goal: 6.5%
HbA1c
Unlimited
AACE Medical Guidelines for the Management of Diabetes Mellitus
 The problem

Hundred years after the discovery of insulin, why are

we still vastly under utilizing one of the true medical
breakthroughs of our century?

Insulin “ last right’s therapy ”

Barriers To Insulin Therapy
“ Unfortunately it is poorly prescribed by so many physicians
who treat diabetes and so unsuccessfully used by so many
individuals who have diabetes “

Zachary T. Bloomgarden, Mount Sinai School of Medicine

Overcoming barriers for Insulin Therapy
“ It is important to try to dispel notions
that insulin therapy is difficult, onerous
or fraught with peril by highlighting it’s
efficacy and the great strides that have
been made in insulin formulations and
delivery devices
Most diabetic patients require
insulin at some point in their life time ”
Purpose of Insulin Therapy
“ Subcutaneous injection of Insulin in
T2DM is designed to supplement
endogenous production of insulin
both in the basal state, to modulate
hepatic glucose production and in
the post prandial state, in which a
surge in insulin release normally
facilitates glucose clearance in to
muscle and fat for storage to allow
intra prandial metabolism ”
 Indian insulin guidelines – initiating insulin
Start insulin

At diagnosis OAD failure

If: If:
• FPG >250 mg/dL • FPG >150 mg/dL
• PPG >300 mg/dL • PPG/RBG >200 mg/dL
• HbA1c >9% • HbA1c >8.5%

Or if patient has: Despite receiving optimal dose of two or three

• Systemic infection OADs
• Sepsis
• Acute myocardial infarction
• Unstable angina
• Diabetic ketoacidosis Other indications if there is systemic infection, sepsis, acute MI,
• Pregnancy unstable angina, DKA/HONK, pregnancy, diabetic kidney disease
• Perioperative care

DKA, diabetic ketoacidosis; FPG, fasting plasma glucose; HONK, hyperosmolar nonketotic
coma; MI, myocardial infarction; OAD, oral antidiabetic drug; PPG, postprandial plasma
glucose; RBS, random blood sugar
INCG. National guidelines on initiation and intensification of insulin therapy with premixed insulin analogues. 2013.
INCG. J Assoc Physicians India 2009:57(Suppl. 1):42–6
The Basal/Bolus Insulin Concept
 Basal Insulin
• In someone without diabetes, the pancreas delivers
a small amount of insulin continuously to cover the
body’s non-food related insulin needs.
• Suppresses glucose production between meals and
overnight
• Nearly constant levels
• 50% of daily needs
 Bolus insulin

• Meal time or prandial insulin

• Limits hyperglycemia after meals
• Immediate rise and sharp peak after 1 hour
• 10 to 20% of total daily requirement at each meal
Normal physiological profile of serum insulin
concentration
50

Mealtime insulin excursions

40 Rapid rise; short duration
Serum insulin (mU/L)

30

20
Flat basal insulin profile
10

0
0800 1200 1600 2000 2400 0400 0800
Time (h)

Breakfast Lunch Dinner

Kruszynska. Diabetologia 1987;30:16

 How to go about it ?
• Fix Fasting First – basal + OAD’s
• Pre Mix – once, twice or thrice a day
• Basal Plus
• Basal bolus
• Insulin Pump
Fix Fasting First
(BIDS)
 Case History
• 55 year old woman with 8-year history of type 2 diabetes
• For last 2 years, has taken metformin 1000 mg bid, pioglitazone 15
mg qd, and glimepiride 4 mg qd
– Seen 4 months ago: A1C 8.0%, BP 130/80, and LDL Cholesterol 125 mg/dL
– Added atorvastatin 10 mg qd, told to intensify diet and exercise
• Weight 78 Kg, height 5’ 5”
• Fasting plasma glucose in the office = 196 mg/dL
• Current A1C = 8.8%
 Fix fasting first
PP
BG

Basal Elevated Fasting Hyperglycemia and HGO

Insulins

Normal Fasting Blood Glucose

Hence need to fix fasting first

 Starting With Basal Insulin: Advantages

• 1 injection with no mixing

• Slow, safe, and simple titration
• Low dosage
• Limited weight gain
• Effective improvement in glycemic control

6-37
 Basal Insulin (BIDS)
• Continue OHA’s in the morning
• Start: 10 units/ 0.1 to 0.2 U/Kg/day at bed time
• Adjust: 2 to 4 U once or twice a week to reach FPG Target
• For Hypo: Determine and address cause
Reduce dose by 4 Units
If A1c is not controlled after FPG becomes normal or dose is
>0.5 U/Kg/day
• Treat PPG Excursions
- Add rapid insulin before main meal
- Pre Mix BD
 Adding Rapid Insulin(basal plus)
• Identify Major Meal
• Start: 4 U/ 0.1 U/Kg - consider decreasing basal by
same dose
• Adjust: by 1to 2 U once or twice a week until targets
are met
• Hypo: Determine and address cause
Reduce dose by 2 to 4 Units
 Change to pre mix BD

• Divide current dose in to 2/3 AM, 1/3 PM

• Adjust: by 1to 2 U once or twice a week until targets
are met
• Hypo: Determine and address cause
Reduce dose by 2 to 4 Units
Next step is basal bolus…
 Next step is basal bolus…
• But we have another option
 Pre Mix Thrice
( Prefer Analogue Mix)
 Basal bolus
• One basal injection to cover Fasting
• Prandial injection to cover each meal
• Mostly 3 to cover break fast, lunch and supper
• Other option would be insulin pump
GLP 1Receptor antagonists
Thank you