Initiation of Basal Insulinnot bolus
INTERNAL TRAINING USE ONLY. NOT FOR DISTRIBUTION.
Basal Analogs Offer Advantages
for Individuals Who Need Basal
Insulin
• Insulin is associated with the greatest
expected decrease in A1C as well as a
high risk for hypoglycemia2
Theoretical insulin profile1
Serum insulin level
Basal analog
• Compared to NPH, basal insulin
analogs provide3,4:
NPH
– Reduced rate of hypoglycemia
– Once-daily dosing in type 2 diabetes
– Similar reduction in FPG
0
Time (h)
24
NPH=neutral protamine Hagedorn.
1. Brunton S et al. J Fam Pract. 2005;54(5):445-452. 2. Inzucchi SE et al. Diabetes Care. 2012;35(6):1364-1379.
3. Duckworth W et al. J Diabetes Complications. 2007;21(3):196-204. 4. Hirsch IB. N Engl J Med. 2005;352(2):174-183.
INTERNAL TRAINING USE ONLY. NOT FOR DISTRIBUTION.
Basal Insulin May Not Cover Postprandial
Excursions
and May Increase Risk for Hypoglycemia
75
Plasma insulin (µU/mL)
Breakfast
High postprandial readings at every meal
because mealtime insulin response is absent
50
Lunch
25
Dinner
Basal insulin
Increased risk for hypoglycemia if diet changes or meals are
missed
0
4:00
8:00
12:00
Garber AJ. Diabetes Obes Metab. 2009;11(suppl 5):14-18.
16:00
20:00
Time
INTERNAL TRAINING USE ONLY. NOT FOR DISTRIBUTION.
24:00
4:00
8:00
“Overbasalization” May Lead
to Inadequate Glycemic Control
• Overbasalization can be described as
continued titration of basal insulin without
any appreciable improvement in glucose
control1
• Continued titration of basal insulin may not
achieve A1C goals and may require a change
in treatment strategy1
• Overbasalization increases the risk of adverse
reactions, such as hypoglycemia2
1. LaSalle JR. J Am Osteopath Assoc. 2010;110(2):69-78. 2. LaSalle JR, Berria R. J Am Osteopath Assoc. 2013;113(2):152-162.
INTERNAL TRAINING USE ONLY. NOT FOR DISTRIBUTION.
A Basal-Bolus Regimen Mimics the
Body’s Physiologic Insulin Response
Normal plasma glucose profile
Rapid-acting insulin analog profile
Long-acting insulin analog profile
BUT--
8
AM-12 PM
12
PM-6 PM
6
PM-12 AM
Adapted from Polonsky KS et al. J Clin Invest. 1988;81(2):442-448.
INTERNAL TRAINING USE ONLY. NOT FOR DISTRIBUTION.
Treat across natural history of Diabetes
Patient-Centric, eventually Precision Medicine
Least # Agents Rx’ing Most # mechanisms Hyperglycemia
NO SU/ Insulin only if don’t respond to 3-4 non-Hypoglycemic Agents
Therapeutic Principles Across
Continuum of Care eg:
Right Drug for Right Patient and vice versa
 DETERMINE INSULIN DEPENDENCY-
(DKA, c-peptide,? Other)
DETERMINE Patient Specific Mechanisms of Hyperglycemia
 Treat ? For prevention/ Treat pre-diabetes
 Treat as many of the Egregious 11 Targets as needed,
with least # of agents, to get lowest sugars/HgA1c as
possible without undue weight gain or hypoglycemia
• Early Combination Therapy- Patient Centric- even 6.57.5 HgA1c
Efficacy, - CV event reduction, Weight Loss
(Not first-second-third line; Not competition between
classes)
 Treat with agents that address FBS AND PPG
 Can Modify therapy after 1m-not 3m-use Fructosamie
 Ideally agents will stabilize, preserve β-cells, the CORE
DEFECT ( NO SU/GLINIDES) Ideally agents will have potential to synergistically
decrease in CV risk factors / outcomes
1. Delay Need for Insulin
2. No need for Early Insulin
3. If need Insulin, Continue
Non-Insulin RX
(Avoids need for Meal-Time
Decrease Risk Hypoglycem
4. Get Patients off insulin w
Philosophy for Reduced Insulin
Need in T2DM
Have more Beta-Cells In Patients with T2DM than we had been Taught
1. No Perfect InsulinExogenous insulin not put in portal system; no fine-tuning a la Beta Cell
2. Leads to Insulin Resistance (suppresses dopamine in ‘biologic clock’ of
hypothalamus)– leads to Increased Weight, Hypoglycemia Risk
3. So Goal of all Insulin Therapy- Least Hypoglycemia, Least Weight Gain
4. Old Logic- use Early Insulin to reduce Glucotoxicity, Lipotoxicity
but GLP-1 RAs and SGLT-2 Inh. do that first day!!, with no weight gain, no
hypoglycemia
5. Therefore no need for Early Insulinuse 3-4 Non-Insulin therapy before go to Basal Insulin;
keep Non-Insulin Therapies and 95% of T2DM won’t need Bolus Insulin
(by avoiding bolus insulin
reduce hypoglycemic risk 85%)
Hypoglycemia In BEGIN BB Trial:
88% of daily hypoglycemia due to bolus insulin
Hypoglycemia with glargine
• Confirmed: 13.6/pt.yr
• Nocturnal: 1.8/pt.yr
• Nocturnal/Confirmed % =
• 13.2% of total
Garber A et al Lancet 2012;
379: 1498-1507
Hypoglycemia with degludec
• Confirmed: 11.1/pt.yr
• Nocturnal: 1.4/pt.yr
• Nocturnal/Confirmed % =
• 12.6% of total
Presentation title
Basal + other Agents% to Goal
So Might one not expect ? 90-95% to goal with 3 agents ? 
And If see Patient Given Early Insulin
get them off insulin

1. If willing to start NCS diet, dec. insulin 25%
2. If hypoglycemic (sx’ic, asymptomatic, dec. insulin
25%
3. Take this new estimated insulin dose requirement:
1.
2.
3.
4.
Dec 25% as strart GLP-1 RA
Dec 20% if start SGLT-2 inhibitor
If estimated dose <12u/d, stop insulin
As loses weight, reduce insulin doses until <12u/d,
Stop Insulin
So Based on above Data and Logic:
1. Hyperinsulinemia may be a pivotal defect
2. All exogenous insulin therapy results in
hyperinsulinemia
3. Hyperisulinemia has adverse CV and Other
Consequences
There becomes a CLEAR Pathophysiologic
Implication to ‘Delay’ Insulin Therapy,
Avoid Early Use,
Avoid Bolus even if need basal Insulin