New Paradigms, Guidelines,
and Evolving Strategies
Achieving A1C and
Glycemic Targets with Insulin
What to Do When Oral Agents Fail
JUAN P. FRIAS, M.D., FACE
Assistant Clinical Professor of Medicine
University of California San Diego
San Diego, CA
ADA/EASD: Managing
Hyperglycemia in Type 2 Diabetes
Initial
Monotherapy
Healthy Eating, Increased Physical Activity, Weight Control
Metformin
Efficacy (A1C)
Hypoglycemia
Weight
Side effects
Cost
High
Low risk
Neutral/loss
GI/lactic acidosis
Low
Two Drug
Combo.
A1C target not achieved after 3 months, proceed to 2-drug combo.
Metformin + (order does not denote specific preference)
SFU
TZD
DPP-4 Inhib.
GLP-1 RA
Insulin
(usually basal)
Efficacy (A1C)
Hypoglycemia
Weight
Side effects
Cost
Three Drug
Combo.
High
Mod. risk
Gain
Hypo.
Low
High
Low risk
Gain
Edema, HF, fx
High
Intermediate
Low risk
Neutral
Rare
High
High
Low risk
Loss
GI
High
Highest
High risk
Gain
Hypo.
Variable
A1C target not met after 3 months, proceed to 3-drug combo.
(order does not denote specific preference)
Adapted from, Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
ADA/EASD: Managing
Hyperglycemia in Type 2 Diabetes
Three Drug
Combo.
A1C target not met after 3 months, proceed to 3-drug combo.
(order does not denote specific preference)
MET +
SFU +
MET +
MET +
TZD +
DPP-4 Inh. +
MET +
GLP-1 RA +
MET +
Insulin
(usually basal)
• TZD, or
• DPP-4-I, or
• GLP-1 RA, or
• Insulin
• SFU or
• DPP-4-I, or
• GLP-1 RA, or
• Insulin
• SFU, or
• TZD, or
• Insulin
• SFU, or
• TZD, or
• Insulin
+
• TZD or
• DPP-4-I, or
• GLP-1 RA
If combination therapy that includes basal insulin has failed to
achieve A1C target after 3-6 months, proceed to a more complex
insulin strategy, usually in combination with 1-2 non-insulin agents
More
Complex
Insulin
Strategies
Insulin
Multiple daily doses
Adapted from, Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
Case #1
►
55 year old woman with 8-year history of type 2 diabetes
►
For last 2 years, has taken metformin 1000 mg bid,
pioglitazone 45 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 20 mg qd, told to intensify diet and
exercise
►
Weight 215 lbs (6 lb gain since last visit), height 5’ 5”,
BMI 36 kg/m2
►
Fasting plasma glucose in the office = 196 mg/dL
►
Current A1C = 8.8%
Question #1
What do you do now?
1) Start a GLP-1 receptor agonist
2) Start a DPP-4 inhibitor
3) Add insulin
4) Reinforce efforts at better nutrition and
increased physical activity
Idealized Profiles of Human Insulin
and Insulin Analogs
Rapid-acting: lispro, aspart, glulisine
Regular insulin
NPH
Insulin detemir
Plasma Insulin
Concentration
Insulin glargine
0:00
2:00 4:00 6:00 8:00 10:00 12:00 14:00 16:00 18:00 20:00 22:00 24:00
Time
Rosenstock J. Goldstein BJ et al, eds. Textbook of Type 2 Diabetes. Martin Dunitz;2003:131-154.
Plank J et al. Diabetes Care. 2005;28:1107-1112.
Consistent Results Using the Treat-to-Target
Method with Glargine as Basal Insulin
Baseline
Study end
9.5
9.0
8.6
8.8
8.7
8.6
8.7
8.5
A1C %
8.0
∆ -1.6
∆ -1.6
∆ -1.7
∆ -2.0
∆ -1.7
7.5
7.0
7.0
7.0
7.0
6.8
7.0
6.5
6.0
5.5
T-T-T1
INSIGHT2
APOLLO3
INITIATE4
Schreiber5
n = 367
n = 206
n = 174
n = 58
n = 12,216
1. Riddle M et al. Diabetes Care 2003;26:3080
2. Gerstein HC et al. Diabetes Med 2006;23:736
3. Bretzel RG et al. Lancet 2008;371:1073
4. Yki-Järvinen H et al. Diabetes Care 2007;30:1364
5. Schreiber SA et al. Diabetes Obes Metab 2007;9:31
Insulin Dosage and FPG During Study
50
40
206
36
30
31
28
175
37
39
44
43
41
200
33
25
20
153
16
150
142
10
135 135
128 125
10
121
118
117
116
0
100
0*
2
4
6
8
10
12
14
Weeks in Study
Mean insulin dose 0.45 U/kg
*Week 0 based on a starting dose of 10 units
Riddle M, Rosenstock J, and Gerich, J. Diabetes Care. 2003;26(11)3080-3086.
16
24
Mean FPG mg/dL (± SE)
Total Daily Dose, Units (± SE)
(Both Treatment Groups)
Events per patient exposure–year
Symptomatic Hypoglycemic Events
1.4
*
*
1.2
NPH
Insulin glargine
*
*
1.0
*
*
Basal
insulin
0.8
*
0.6
0.4
0.2
Breakfast
Lunch
Dinner
0
20
22
24
2
4
6
8
10
12
Time of day (h)
Hypoglycaemia defined as plasma glucose 72 mg/dL
*P<0.05 vs insulin glargine
Adapted from Riddle M, et al. Diabetes Care. 2003;26:3080-3086. Used with permission.
14
16
18
Detemir vs NPH Insulin in Type 2
Diabetes (n=476)
Detemir
NPH
10.0
Detemir
NPH
9.0
8.0
7.0
6.0
Hypoglycemia Events*
400
A1C (%)
350
300
250
200
150
100
50
0
-2 0
4
8 12 16 20 24
Study Week
024
8 12 16 20 24
Study Week
*All reported events, including symptoms only.
Hermansen K et al. Diabetes Care. 2006;29:1269-1274.
Percentage of Patients Reaching Target
A1C at Week 24 by Baseline A1C
Baseline A1C Group
n
Mean Baseline A1C
581
436
360
327
608
7.6
8.2
8.7
9.2
10.2
Riddle M et al. ADA abstract 468-P. Diabetes. 2009;58(suppl 1):A125.
Exenatide QW Resulted in Superior A1C
Reduction vs. Insulin Glargine
Exenatide QW, N=233; baseline A1C=8.3%
Insulin glargine, N=223; baseline A1C=8.3%
0.0
Change in A1C (%)
-0.2
-0.4
-0.6
-0.8
-1.0
*
-1.2
-1.3%
-1.4
-1.6
*
*
*
14
18
22
*
-1.8
0
8
Time (weeks)
ITT Population, N=456. *p<0.05
Diamant M, et al. Lancet. 2010;375:2234-43.
26
-1.5%
Exenatide QW Resulted in Superior Body
Weight Reduction vs. Insulin Glargine
Exenatide QW, N=233; baseline weight=91 kg
Insulin glargine, N=223; baseline weight=91 kg
Change in Body Weight (kg)
2
+1.4 kg
1
0
*
-1
*
-2
*
*
-3
012
4
8
14
18
Time (weeks)
ITT Population, N=456. *p<0.05
Diamant M, et al. Lancet. 2010;375:2234-43.
*
22
-2.6 kg
*
26
Case #1 (cont.)
►
20 U insulin glargine (~0.2 U/kg) is added to her
oral agents
►
Sent home with instructions to increase dose by 2U
every 3 days until FBG in 100-120 mg/dL range
►
Call if any hypoglycemia and follow-up by phone or
in clinic in 1 week
Should you reduce or stop one of
the oral agents?
Riddle MC et al. Diabetes Care. 2003;26:3080-3086.
Hermansen K et al. Diabetes Care. 2006;29:1259-1271.
Nathan DM, et al. Diabetes Care 2009;32:193–203.
Case #1 (cont.)
►
Patient is up to 52 U with fasting blood glucose
controlled (100-110 mg/dL range) since her last
visit 4 months ago
►
A1C = 6.7%, monitoring occasional postprandial
blood glucose
►
Patient finds insulin injections painless and after
working with diabetes educator, feels that she is
now a partner in her own therapy
“Fix the Fasting First”
►
Even if you are not certain basal insulin alone will
achieve target A1C (e.g. patient with A1C >10%), it
is generally preferable to begin with it & add a
rapid-acting analog with the largest meal, if needed.
►
It is easier for the HCP & patient to see which
insulin needs to be adjusted
Basal Insulin Therapy
►
Usual first step in beginning insulin therapy
►
Continue oral agents and add basal insulin to optimize FPG
►
A1C of up to 9.0% usually brought to goal (7%) by
addition of basal insulin therapy to oral agents
►
Easy and generally safe: patient-directed treatment
algorithms with small risk of serious hypoglycemia
►
ADA and EASD: ”If triple combination therapy exclusive of
insulin is tried, the patient should be monitored closely,
with the approach promptly reconsidered if it proves
unsuccessful”
ADA=American Diabetes Association; EASD=European Association for the Study of Diabetes.
ADA/EASD Management of hyperglycemia in type 2 diabetes: A patient-centered approach. 19 April 2012 [Epub ahead of print]
New Paradigms, Guidelines,
and Evolving Strategies
Case Presentation #2:
Strategies for Advancing to
Postprandial Glucose Control
ADA/EASD: Managing
Hyperglycemia in Type 2 Diabetes
Three Drug
Combo.
A1C target not met after 3 months, proceed to 3-drug combo.
(order does not denote specific preference)
MET +
SFU +
MET +
MET +
TZD +
DPP-4 Inh. +
MET +
GLP-1 RA +
MET +
Insulin
(usually basal)
• TZD, or
• DPP-4-I, or
• GLP-1 RA, or
• Insulin
• SFU or
• DPP-4-I, or
• GLP-1 RA, or
• Insulin
• SFU, or
• TZD, or
• Insulin
• SFU, or
• TZD, or
• Insulin
+
• TZD or
• DPP-4-I, or
• GLP-1 RA
If combination therapy that includes basal insulin has failed to
achieve A1C target after 3-6 months, proceed to a more complex
insulin strategy, usually in combination with 1-2 non-insulin agents
More
Complex
Insulin
Strategies
Insulin
Multiple daily doses
Adapted from, Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
Sequential Insulin Strategies in
Type 2 Diabetes
Non-Insulin Regimen
Number Complexity
of
of
injections regimen
Basal Insulin only
1
Low
2
Mod
3+
High
(usually with oral agents)
Basal insulin + 1 (mealtime)
rapid-acting insulin injection
Pre-mixed insulin twice daily
Basal insulin + ≥2 (mealtime)
rapid-acting insulin injection
More Flexible
Less Flexible
Adapted from, Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
Case #2
►
50-year-old man with 6-year history of type 2 diabetes
►
295 lb, 6’ 1”, BMI 39 kg/m2
►
For last 2 years, has taken metformin 1000 mg bid and
glimepiride 8 mg qd
►
3 months ago, A1C 9.2%
►
Started a twice-daily premixed analog insulin (70/30);
current dose 40 U bid
Case #2 (cont.)
►
Current A1C 7.5% and random plasma glucose in
the office 185 mg/dL
►
Patient experiencing nighttime hypoglycemia
(reports middle-of-night sweating)
►
SMBG diary focused on fasting glucose
►
Patient instructed to measure glucose before meals,
at bedtime, and during night for a week
Case #2 (cont.)
Question #2
Patient’s A1C is 7.5% and SMBG diary reveals high
fasting and post-dinner glucose, and nocturnal
hypoglycemia. The next step for this patient to gain
control is to:
1) Continue with the twice-daily premix and increase
dose
2) Continue with premixed and discontinue glimepiride
3) Switch to a long-acting insulin analog alone
4) Basal insulin + GLP-1 receptor agonist
5) Switch to a basal-bolus insulin regimen
Basal/Bolus Treatment Program With
Rapid-acting and Long-acting Analogs
Breakfast
Lunch
Aspart
Aspart
Aspart
Lispro
Lispro
Lispro
or
or
or
Plasma
Insulin
Dinner
Glulisine
or
Glulisine
or
or
Glulisine
Glargine
or
Detemir
4:00
8:00
12:00
16:00
Time
20:00
24:00
4:00
8:00
“All to Target” Trial
Insulin Glargine + Glulisine on to Background Orals
►
►
572 patients with type 2 diabetes uncontrolled on oral agents
●
PREMIX: n=192
●
GLARG+1: n=189
●
GLARG+0-3: n=191
Mean baseline parameters:
●
A1C 9.4%
●
Age 54 years
●
Diabetes duration 9 years
●
BMI 33 kg/m2
“All to Target” study, Diabetes. 2011;60(suppl 1), 409-P, 073-OR
Insulin Glargine + Glulisine:
A1C and Hypoglycemia
a
b
c
a
p < 0.025 versus PREMIX
b
p < 0.05 versus PREMI
d
c
p < 0.05 versus PREMIX
p < 0.01 versus PREMIX
“All to Target” study, Diabetes. 2011;60(suppl 1), 409-P, 073-OR
d
Case #2 (cont.)
►
Patient to switch to basal-bolus insulin therapy:
●
►
After 3 months, patient remains on metformin +
glimepiride, and is using 62 U glargine daily
●
►
First step, patient starts with 40 U insulin glargine
A1C now 7.2%
Asked to repeat SMBG profiles prior to next visit
Case #2 (cont)
Question #3
Patient’s A1C is approaching target, but not fully
there. What is next for this patient?
1) Continue basal insulin and increase dose
2) Continue basal insulin and initiate prandial
insulin
3) Add GLP-1 receptor agonist to basal insulin
4) Return to twice-daily premix at lower dose
5) Continue basal insulin and recommend diabetes
education to advise on controlling diet
Mealtime Insulin: Rapid-Acting Analogs
(Lispro, Aspart, Glulisine) vs Regular
Analog insulin
Insulin Activity
10
8
6
4
Human regular
Timing of
food
absorbed
2
0
0
1
2
3
4
5
6
Hours
Adapted with permission from Howey DC et al. Diabetes. 1994;43:396-402.
7
8
9
10
11
12
Insulin Glargine + Exenatide
Buse,JB Ann Int Med 154:103, 2011
Question #4
How do you start dosing a short-acting analog
at dinner?
1) Up to 4-6 U pre-meal
2) Use sliding scale
3) By body weight: 0.1 U/kg
4) By carbohydrate counting
Case #2 (cont.)
►
At 6-month follow-up patient is doing well with
56 U glargine and 14-18 U glulisine at dinner
►
Mealtime dose occasionally adjusted based on:
●
●
Meal carbohydrate content
Activity
►
A1C = 6.3%
►
He feels well, has infrequent “hypos”, and is
pleased with his BG control
Case #2 (cont.)
►
Continue follow-up with patient
►
Over time, if postprandial glucose becomes
elevated at meals other than dinner, add premeal insulin at that meal
Basal-Bolus Insulin Replacement:
Summary
►
An effective insulin treatment strategy provides
both basal and prandial insulin coverage
►
Initially, prandial insulin may be needed only at
the largest meal of the day, with coverage at
other meals added based on postprandial glucose
concentrations
►
Rapid-acting insulin analogs more closely match
post-meal carbohydrate absorption
Insulin Therapy in Type 2 Diabetes:
Conclusions
►
Most patients will ultimately need insulin therapy alone or
in combination with other agents to maintain glycemic
control
►
The most convenient strategy for initiating insulin is
starting with a single dose of basal insulin
►
Addition of prandial insulin should be considered when
significant postprandial glucose excursions occur (e.g.,
>180 mg/dL), staring with the meal with the largest
postprandial glucose excursion
►
Side effects (risk of hypoglycemia and weight gain) must
be addressed with patient, and appropriate follow-up
scheduled
New Paradigms, Guidelines,
and Evolving Strategies
Case Studies, Clinical Dilemmas, and
2012 ADA/EASD Guidelines for
Diabetes Management
Focus On Insulin-based Approaches
Workshop Interactive, ARS Session
VIVIAN A. FONSECA, MD, FRCP
Program Chairman
Professor of Medicine and Pharmacology | Tulis-Tulane
Alumni Chair in Diabetes | Chief, Section of Endocrinology |
Tulane University Health Sciences Center
Case Studies and Clinical Dilemmas
1. Less stringent A1c goals may be appropriate for
which of the following patients?
1) Patients with advanced microvascular complications
2) Patients with advanced macrovascular complications
3) Patients with extensive comorbid conditions
4) All of the above patients may qualify for less stringent
A1c goals
5) None of the above patients qualify for less stringent A1c
goals
Case Studies and Clinical Dilemmas
2. With respect to recommendations contained in the
new ADA/EASD Guidelines issued on April 19, 2012, all
of the following are true for managing older patients
with T2D, EXCEPT:
1) The focus should be on achieving specific glycemic
targets
2) The focus should be on drug safety
3) The patient should be invited to participate in the
treatment decisions
4) Less ambitious glycemic targets can be considered in the
older patient
5) Glycemic targets less than 7.5%-8.0% can be considered
if tighter control is not easily achieved
ADA-EASD Position Statement:
Management of Hyperglycemia in T2DM
OTHER CONSIDERATIONS
 Age: Older adults





Reduced life expectancy
Higher CVD burden
Reduced GFR
At risk for adverse events from polypharmacy
More likely to be compromised from hypoglycemia
Less ambitious targets
HbA1c <7.5–8.0% if tighter targets
not easily achieved
Focus on drug safety
Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
Case Studies and Clinical Dilemmas
3. Which of the following statements regarding key
considerations in the management of type 2 diabetes
is FALSE?
1) The mechanisms driving hyperglycemia change with
duration of the disease
2) The loss of beta cell function drives the full expression of
the disease
3) Clinical inertia often results in prolonged exposure to
hyperglycemia, thereby leading to increased risk of
complications
4) Maximizing doses of first- and second-line agents before
introducing additional therapies will always improve
adherence and clinical outcomes
Case Studies and Clinical Dilemmas
4. AJ is a 58-year old man with a recent history of
type 2 diabetes. After being well controlled on
metformin (2000 mg per day) treatment alone for 1
year, his latest A1c is 8.2%. Which of the following
treatment options would be LEAST appropriate for AJ?
1) Increase his dose of metformin
2) Add a sulfonylurea to his treatment regimen
3) Add basal insulin to his treatment regimen
4) Add a GLP-1 agonist to his treatment regimen
Diabetes Care, Diabetologia. 19 April 201
T2DM Antihyperglycemic Therapy: General Recommendations[Epub ahead of print]
Progressive Platform Approach (PPA) to
Glycemic Control
A Practice-Oriented Analysis of 2012 ADA/EASD 2012 Guidelines
Platform 1: Lifestyle Changes Plus Oral Foundation Agents

Most patients will be started on the oral agent metformin, and if
individualized target goals are not met promptly, an additional oral agent
may be tried; or alternatively, a basal insulin is "usually" employed as the
starting insulin.

As a general rule, the use of more than two oral agents may not be optimal,
and consideration to insulin or a GLP-1 agonist should be given if target
goals are not reached with intensification of oral therapy.

Treatment choices, at least in part, will depend on how far from goal the
patient is.
Inadequate Treatment
Response
Progress to Next
Platform
Progressive Platform Approach (PPA) to
Glycemic Control
A Practice-Oriented Analysis of 2012 ADA/EASD 2012 Guidelines
Platform 2: Oral Foundation Agents Plus Basal Insulin
 If individualized target goal attainment fails with one or two oral agents,
typically the management plan will focus on a combined oral-insulin based
regimen, or the addition of a GLP-1 agonist.
 Usually, the foundation insulin for beginning therapy for platform 2 will be a
basal insulin.
 Glycemic control with oral agents individualized to patient's needs plus a basal
insulin will frequently be a sustainable regimen for many patients with T2D.
 Treatment choices, at least in part, will depend on how far from goal the
patient is.
Inadequate Treatment
Response
Progress to Next
Platform
Progressive Platform Approach (PPA) to
Glycemic Control
A Practice-Oriented Analysis of 2012 ADA/EASD 2012 Guidelines
Platform 3: Multi-Insulin Regimen
 If individualized glycemic targets cannot be maintained on the
combination of oral agents plus basal insulin or GLP-1 agonist,
shorter-acting insulin formulations may need to be added to basal
insulin to address post-prandial glycemic control. Insulin sensitizers
may need to be continued.
 Platform 3 therapy will generally require titration of multi-insulin
regimens to achieve glycemic control in patients who have
progressive T2D and have failed a combined oral agent-basal insulin
+/- GLP-1 agonist regimen.
 Bariatric surgery may be considered as an option, particularly when
medical therapy is clearly failing in obese patients.
Case Studies and Clinical Dilemmas
5. Which of the following statements about recent clinical trial
findings related to the use of insulin in patients with type 2
diabetes is FALSE?
1) In a substudy of the UKPDS, patients with newly diagnosed type 2
diabetes demonstrated that early addition of insulin to oral agent
monotherapy maintained glucose levels below target for 6 years
2) In the Treat-to-Target trial, glargine and NPH insulin demonstrated
equivalent efficacy when added to 1 or 2 oral agents in type 2
diabetes
3) In the Treat-to-Target trial, rates of hypoglycemia were significantly
lower with glargine than with NPH
4) In a recent study that examined the strategy of adding basal insulin
versus a third oral agent to oral combination therapy with metformin
and sulfonylurea, it was demonstrated that overall A1c reductions
were significantly better with a maximal dose of rosiglitazone than
with a low dose of insulin glargine
Case Studies and Clinical Dilemmas
6. BP is a 42-year old man who was diagnosed with
diabetes and started on metformin therapy 4 months ago.
His current HbA1c is 8.2%. According to the ADA/EASD
consensus algorithm, which of the following would be the
LEAST appropriate next step in therapy for BP?
1) Add a sulfonylurea
2) Add basal insulin glargine
3) Add a glitazone
4) Add postprandial insulin
Case Studies and Clinical Dilemmas
7. Which of the following statements about the
pharmacokinetic characteristics of insulin glargine is
FALSE?
1) Peak action occurs at approximately 5-7 hours from
administration
2) Duration of action is approximately 24 hours
3) Glargine produces a flat action profile similar to that if
continuous subcutaneous insulin infusion
4) Onset of action is approximately 2 hours
Case Studies and Clinical Dilemmas
8. When the goal is to “minimize costs,” the new
ADA/EASD Guidelines issued on April 19, 2012 for
management of T2D suggest:
1) The combination of metformin plus a DPP-4 inhibitor
2) The combination of metformin plus a GLP-1 receptor
agonist
3) The combination of metformin plus a insulin (usually
basal)
4) The combination of metformin plus a thiazolidine-dione
5) All of the above
6) None of the above
Case Studies and Clinical Dilemmas
9. Which of the following statements regarding insulin
glargine in type 2 diabetes is TRUE?
1) Clinical trials have demonstrated significant intra-patient
variability
2) Studies demonstrate that once-daily insulin glargine was
less effective than NPH insulin given once or twice daily
in reducing A1c levels
3) Clinical trials have demonstrated that nocturnal
hypoglycemia was less frequent when using insulin
glargine than with NPH insulin
4) Studies show that when compared to NPH insulin, insulin
glargine use resulted in more weight gain
ADA-EASD Position Statement:
Management of Hyperglycemia in
T2DM
ANTI-HYPERGLYCEMIC THERAPY
 Therapeutic options: Insulin
 Neutral protamine Hagedorn (NPH)
 Regular
 Basal analogues (glargine, detemir)
 Rapid analogues (lispro, aspart, glulisine)
 Pre-mixed varieties
Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
ADA-EASD Position Statement:
Management of Hyperglycemia in
T2DM
ANTI-HYPERGLYCEMIC THERAPY
Therapeutic options: Insulin
Insulin level
Rapid (Lispro, Aspart, Glulisine)
Short (Regular)
Intermediate (NPH)
Long (Detemir)
Long (Glargine)
0
2
4
6
8
10
12
14
Hours after injection
16
18
20
22
24
Case Studies and Clinical Dilemmas
10. The new ADA/EASD Guidelines issued on April 19,
2012 for management of T2D recommend or indicate
all of the following EXCEPT:
1) Unless it is contraindicated, metformin is the optimal first-line
drug
2) Comprehensive CV risk reduction is a major focus of therapy
3) The combination of metformin, plus the addition of at least
two other appropriately selected oral agents, should precede
use of insulin
4) The combination of metformin plus insulin (usually basal) is an
appropriate second step in patients not achieving targets on
5) None of the above is correct
Case Studies and Clinical Dilemmas
11. Which of the following options is the LEAST
appropriate way to initiate basal insulin in a patient
with type 2 diabetes?
1) Start with 10 units of bedtime insulin glargine
2) Start with 10 units of morning NPH insulin
3) Start with 10 units of morning insulin glargine
4) Start with 10 units of bedtime insulin detemir
Case Studies and Clinical Dilemmas
12. Which of the following statements regarding the early
initiation, addition, or intensification of insulin therapy in type 2
diabetes is FALSE?
1) Early insulin therapy has been shown to have beneficial
effects on short-term glycemic control but little effect on
long-term control
2) Short-term positive effects of early insulin initiation is
explained by rapid reduction of glucotoxicity
3) Early initiation of insulin therapy may lead to immediate
improvement in beta-cell function
4) Initiation of insulin therapy, after failure of lifestyle
modification and an oral agent, is one option
recommended in the ADA guidelines
Sequential Insulin Strategies in T2DM
Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of prin
Case Studies and Clinical Dilemmas
13. All of the following are potential barriers
associated with insulin initiation in diabetes, EXCEPT:
1) Potential for hypoglycemia
2) Weight gain
3) Potential for unpredictable action of long-acting
formulations
4) Improved cognitive function with oral agents
Case Studies and Clinical Dilemmas
14. When initiating insulin therapy in patients with
type 2 diabetes, patients should be advised to
maintain regular eating habits and exercise schedules,
centered around their insulin treatment regimen.
1) True
2) False
Case Studies and Clinical Dilemmas
15. TK is a 64-year old woman with a 3-year history of type 2
diabetes. Despite losing 10 pounds in the past year, her most
recent A1c is 7.9%.
Her current medication regimen includes metformin and a
sulfonylurea.
You decide to add insulin treatment to her regimen. Which of
the following is the MOST appropriate next step in therapy for
TK?
Case Studies and Clinical Dilemmas
1) Start with bedtime intermediate-acting insulin; check fasting
glucose weekly and increase dose until fasting levels are in
target range; check A1c in 6 months
2) Start with morning basal insulin; check fasting glucose daily
and increase dose until fasting levels are in target range;
check A1c in 6 months
3) Start with bedtime basal insulin; check fasting glucose daily
and increase dose slowly until fasting levels are in target
range; check A1c in 3 months
4) Start with morning intermediate-acting insulin; check fasting
glucose daily until fasting levels are in target range; check
A1c in 3 months
Case Studies and Clinical Dilemmas
16. Rapid-acting insulin analogues control postprandial glucose levels better than regular insulin, but
cause more hypoglycemia.
1) True
2) False
Case Studies and Clinical Dilemmas
17. In which of the following patients with type 2 diabetes
would it be MOST appropriate to initiate insulin therapy?
1) A newly diagnosed 80-year old patient who is treatment
naïve
2) A patient who has been on metformin monotherapy for 6
months with an A1c of 7%, who is prone to
hypoglycemic episodes
3) A newly diagnosed 58-year old patient with severe
hyperglycemia at diagnosis
4) All of the above would be good candidates for insulin
therapy
5) None of the above would be good candidates for insulin
therapy
Case Studies and Clinical Dilemmas
18. GG is a 68-year old woman with a 3-year history of type 2
diabetes. Her A1c is 8.1% and she is currently on metformin, a
sulfonylurea, and bedtime basal insulin. Her fasting plasma
glucose levels are consistently around 110 mg/dL and her
postprandial levels are around 180 mg/dL. Which of the
following is the MOST appropriate next step in therapy for GG?
1) Increase her dose of basal insulin by 4 units and
continue to monitor her fasting glucose daily
2) Discontinue her basal insulin and initiate treatment with
a GLP-1 receptor agonist
3) Increase her dose of basal insulin by 2 units and add a
pre-meal rapid-acting insulin
4) Add a rapid acting insulin before the largest meal with or
without discontinuing her sulfonylurea
ADA-EASD Position Statement:
Management of Hyperglycemia in
T2DM
KEY POINTS
 Glycemic targets & BG-lowering therapies must be individualized.
 Diet, exercise, & education: foundation of any T2DM therapy program
 Unless contraindicated, metformin = optimal 1st-line drug.
 After metformin, data are limited. Combination therapy with 1-2 other
oral / injectable agents is reasonable; minimize side effects.
 Ultimately, many patients will require insulin therapy alone / in
combination with other agents to maintain BG control.
 All treatment decisions should be made in conjunction with the patient
(focus on preferences, needs & values).
 Comprehensive CV risk reduction - a major focus of therapy.
Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]