1. Initiation of Basal Insulin- not bolus
Review as stated
INTERNAL TRAINING USE ONLY. NOT FOR DISTRIBUTION.

2. Basal Analogs Offer Advantages for Individuals Who Need Basal Insulin
From PRB : Getting Patients to Goal: When Is It Time to Intensify With Insulin?(Pending final approval) -Updated formatting, added training disclaimer
Basal Analogs Offer Advantages for Individuals Who Need Basal Insulin
Inzucchi
P4-5 Table 1
Theoretical insulin profile1
NPH
Basal analog 24
Time (h)
Serum insulin level
Insulin is associated with the greatest expected decrease in A1C as well as a high risk for hypoglycemia2
Compared to NPH, basal insulin analogs provide3,4:
Reduced rate of hypoglycemia
Once-daily dosing in type 2 diabetes
Similar reduction in FPG
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 hypoglycemia1
Compared to NPH, long-acting insulin analogs provide a reduced rate of hypoglycemia, once-daily dosing in type 2 diabetes, and a similar reduction in FPG2,3
A theoretical basal analog and NPH profile over 24 hours is shown here4
References
Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach: Position Statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2012;35(6):
Duckworth W, Davis SN. Comparison of insulin glargine and NPH insulin in the treatment of type 2 diabetes: a review of clinical studies. J Diabetes Complications. 2007;21(3):
Hirsch IB. Insulin analogues. N Engl J Med. 2005;352(2):174–183.
Brunton S, Carmichael B, Funnell M, Lorber D, Rakel R, Rubin R. Type 2 diabetes: the role of insulin. J Fam Pract. 2005;54(5):
NPH=neutral protamine Hagedorn.
1. Brunton S et al. J Fam Pract. 2005;54(5): Inzucchi SE et al. Diabetes Care. 2012;35(6):
3. Duckworth W et al. J Diabetes Complications. 2007;21(3): Hirsch IB. N Engl J Med. 2005;352(2):
INTERNAL TRAINING USE ONLY. NOT FOR DISTRIBUTION.

3. From PRB approved : Why Mealtime Matters – Updated formatting, added training disclaimer
Basal Insulin May Not Cover Postprandial Excursions and May Increase Risk for Hypoglycemia
Time
Plasma insulin (µU/mL) 75 50 25
4:00
8:00
12:00
16:00
20:00
24:00
Basal insulin
Dinner
Lunch
Breakfast
High postprandial readings at every meal
because mealtime insulin response is absent
Increased risk for hypoglycemia if diet changes or meals are missed
Basal Insulin May Not Cover Postprandial Excursions and May Increase Risk for Hypoglycemia
High levels of basal insulin therapy may not provide PPG control
In this hypothetical diagram, normal insulin physiology is represented by yellow curves. If basal insulin is raised to high levels (red line), high postprandial readings remain, and there is an increased risk for hypoglycemia if diet changes or meals are missed and insulin levels are too high
Reference
Garber AJ. Insulin intensification strategies in type 2 diabetes: when one injection is no longer sufficient. Diabetes Obes Metab. 2009;11(suppl 5):14-18.
Garber AJ. Diabetes Obes Metab. 2009;11(suppl 5):14-18.
INTERNAL TRAINING USE ONLY. NOT FOR DISTRIBUTION.

4. “Overbasalization” May Lead to Inadequate Glycemic Control
From PRB approved : Teaching Patients to Self-Titrate Rapid-Acting Insulin – Updated formatting, added training disclaimer
“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
“Overbasalization” May Lead to Inadequate Glycemic Control
Multiple steps can be taken to identify patients who may be overbasalized and may require prandial insulin
When the titration of basal insulin achieves a fasting glucose level between 80 and 100 mg/dL and the patient is still not at A1C goal, a more intensive therapy needs to be initiated to control postprandial blood glucose
In some patients, basal insulin exceeds 50% of the estimated required daily insulin dose without achieving fasting plasma glucose goals
Reference
LaSalle JR. Empowering patients during insulin initiation: a real-world approach. J Am Osteopath Assoc. 2010;110(2):69-78.
1. LaSalle JR. J Am Osteopath Assoc. 2010;110(2): LaSalle JR, Berria R. J Am Osteopath Assoc. 2013;113(2):
INTERNAL TRAINING USE ONLY. NOT FOR DISTRIBUTION.

5. A Basal-Bolus Regimen Mimics the Body’s Physiologic Insulin Response
From PRB approved : Approaches in Managing Mealtime Insulin: Why and When – Updated formatting, added training disclaimer
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--
A Basal-Bolus Regimen Mimics the Body’s Physiologic Insulin Response
Basal-bolus insulin therapy can mimic a body’s physiologic insulin response with rapid-acting insulin (orange line) covering meals and long-acting insulin (green line) providing coverage for up to 24 hours
As you can see by the chart, this insulin strategy matches the body’s normal glucose profile (blue lines)
Reference
Polonsky KS, Given BD, Van Cauter E. Twenty-four-hour profiles and pulsatile patterns of insulin secretion in normal and obese subjects. J Clin Invest. 1988;81(2):
8 AM-12 PM
12 PM-6 PM
6 PM-12 AM
Adapted from Polonsky KS et al. J Clin Invest. 1988;81(2):
INTERNAL TRAINING USE ONLY. NOT FOR DISTRIBUTION.

6. . Treat with Least Number of agents that address most Number of Mechanisms of hyperglycemia 2. Treat across natural history of Diabetes Delay Need for Insulin No need for Early Insulin If need Insulin, Continue Non-Insulin RX OR WITH USE NEW GLP-1 BASAL COMBO (Avoids need for Meal-Time Insulin- (Decrease Risk Hypoglycemia 85%- Garber) 4. Get Patients off insulin who had been given early Insulin
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

7. 2. No need for Early Insulin 3. If need Insulin, Continue
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 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 Insulin-
Decrease Risk Hypoglycemia 85%-
4. Get Patients off insulin who had
been given early Insulin

8. Philosophy for Reduced Insulin Need in T2DM
Have more Beta-Cells In Patients with T2DM than we had been Taught
1. No Perfect Insulin-
Exogenous 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 Insulin-
use 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%)

9. Hypoglycemia In BEGIN BB Trial: 88% of daily hypoglycemia due to bolus insulin
Hypoglycemia with glargine
Hypoglycemia with degludec
Confirmed: 13.6/pt.yr
Nocturnal: /pt.yr
Nocturnal/Confirmed % =
13.2% of total
Confirmed: 11.1/pt.yr
Nocturnal: /pt.yr
Nocturnal/Confirmed % =
12.6% of total
Garber A et al Lancet 2012; 379:
Presentation title

10. So Might one not expect ? 90-95% to goal with 3 agents ? 
Basal + other Agents% to Goal
So Might one not expect ? 90-95% to goal with 3 agents ? 

11. And If see Patient Given Early Insulin get them off insulin 
If willing to start NCS diet, dec. insulin 25%
If hypoglycemic (sx’ic, asymptomatic, dec. insulin 25%
Take this new estimated insulin dose requirement:
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

12. 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