Patient Case Discussion in Type 2 Diabetes

Patient Case Discussion
in Type 2 Diabetes
What Intensification Plan is Best?

Outline
• Introduction
• Diagnostic Criteria
• Treatment Goals
• Intensification Guidelines
• Changes in Lifestyle and Exercise.
• Oral Agents.
• Basal Insulin Analogs.

• Insulin Intensification
• Case Presentations
2

Introduction
• Type 2 Diabetes Mellitus (Defn??)
• Important to stay 1 step ahead
of T2DM.
• Intensifying antihyperglycemic
therapy requires:
• Guideline recommendations (ADA
& AACE).
• Safe and effective plans based on
individual cases.

• Intensification in order to meet
certain goal.
3

Introduction
• Diabetes is not a
quick fix.
• Regular follow-ups
needed.

• Treatment adherence
is crucial.
• Discuss goals of
treatment.
• Educate patients.

4

Diagnostic criteria
• Fasting Plasma Glucose.
• Impaired Fasting Glucose.
• Impaired Glucose Tolerance.
• Plasma Glucose.
• Glycated Hemoglobin.

5

Treatment Goals: Nonpregnant Adults
(Out Patient)
Parameter

A1C (%)

Treatment Goal
Individualize on the basis of age,
comorbidities, duration of disease, and
hypoglycemia risk:
• In general, ≤6.5 for most*
• Closer to normal for healthy
• Less stringent for “less healthy”

FPG (mg/dL)

<110

2-Hour PPG (mg/dL)

<140

*Provided target can be safely achieved.
FPG = fasting plasma glucose; PPG = postprandial glucose.

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Treatment Goals: Pregnant Women
(Out Patient)
Condition

Treatment Goal

Gestational diabetes mellitus (GDM)
Preprandial glucose, mg/dL

≤95*

1-Hour PPG, mg/dL

≤140*

2-Hour PPG, mg/dL

≤120*

Preexisting T1D or T2D
Premeal, bedtime, and overnight glucose,
mg/dL
Peak PPG, mg/dL
A1C

60-99*
100-129*
≤6.0%*

*Provided target can be safely achieved.
FPG = fasting plasma glucose; PPG = postprandial glucose.

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Treatment Goals: Nonpregnant Adults
(In Patient)
Hospital Unit

Treatment Goal

Intensive/critical care
Glucose range, mg/dL

140-180*

General medicine and surgery, non-ICU
Premeal glucose, mg/dL

<140*

Random glucose, mg/dL

<180*

*Provided target can be safely achieved.
ICU = intensive care unit.

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Intensification Guidelines
• Is a principle which
emphasize patient should be
treated based on:
• Age
• Degree of complication
• Other co-morbid conditions

Oral Agents

Lifestyle
Change
and
Exercise

Intensificati
on Therapy

Basal
Insulin
Analogs

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Changes in Lifestyle and Exercise
• Lifestyle
management is an
integral part of T2DM
management.
• Realistic plan for diet
and physical activity
is necessary.

T2DM incidence
per 100 person-years

12

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31%

10
8
6

58%

7.8

4.8

4
2
0

Intensive lifestyle
intervention*
(n=1079)

Metformin
850 mg BID
(n=1073)

Placebo
(n=1082)

*Goal: 7% reduction in baseline body weight through low-calorie, low-fat diet and ≥150 min/week moderate intensity exercise.
DPP, Diabetes Prevention Program; IGT, impaired glucose tolerance; T2D, type 2 diabetes.
DPP Research Group. N Engl J Med. 2002;346:393-403.

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Oral Agents

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Oral Agents
Class
-Glucosidase
inhibitors
Amylin analogue

Biguanide
Bile acid
sequestrant

Primary Mechanism of Action
 Delay carbohydrate
absorption from intestine
 Decrease glucagon secretion
 Slow gastric emptying
 Increase satiety
 Decrease HGP
 Increase glucose uptake in
muscle
 Decrease HGP?
 Increase incretin levels?

Agent(s)
Acarbose
Miglitol

Available as
Precose or generic
Glyset

Pramlintide

Symlin

Metformin

Glucophage or
generic

Colesevelam

WelChol



Alogliptin
Linagliptin
Saxagliptin
Sitagliptin
Bromocriptin
e
Nateglinide
Repaglinide

Nesina
Tradjenta
Onglyza
Januvia

DPP-4 inhibitors


Increase glucose-dependent
insulin secretion
Decrease glucagon secretion

Dopamine-2
agonist



Activates dopaminergic
receptors

Glinides



Increase insulin secretion

Cycloset
Starlix or generic
Prandin

DPP-4 = dipeptidyl peptidase; HGP = hepatic glucose production.
Garber AJ, et al. Endocr Pract. 2013;19(suppl 2):1-48. Inzucchi SE, et al. Diabetes Care. 2012;35:1364-1379.

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Oral Agents
Class
GLP-1 receptor
agonists

SGLT2 inhibitors

Sulfonylureas

Thiazolidinedione
s

Primary Mechanism of Action
 Increase glucose-dependent
insulin secretion
 Decrease glucagon secretion
 Slow gastric emptying
 Increase satiety

Agent(s)

Available as

Albiglutide
Dulaglutide
Exenatide
Exenatide XR
Liraglutide

Tanzeum
Trulicity
Byetta
Bydureon
Victoza

Increase urinary excretion of
glucose

Canagliflozin
Dapagliflozin
Empagliflozin

Invokana
Farxiga
Jardiance



Increase insulin secretion

Glimepiride
Glipizide
Glyburide



Amaryl or generic
Glucotrol or
generic
Diaeta, Glynase,
Micronase, or
generic

Increase glucose uptake in
muscle and fat
Decrease HGP

Pioglitazone
Rosiglitazone

Actos
Avandia





GLP-1 = glucagon-like peptide; HGP = hepatic glucose production; SGLT2 = sodium glucose cotransporter 2.
Garber AJ, et al. Endocr Pract. 2013;19(suppl 2):1-48. Inzucchi SE, et al. Diabetes Care. 2012;35:1364-1379.

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Intensification Plan: Mono, Dual, and
Triple Therapy for T2DM
Monotherapy*

Dual therapy*

Triple therapy*

Metformin (or other
first-line agent) plus

First- and secondline agent plus

Metformin

GLP1RA

GLP1RA

GLP1RA

SGLT2I

SGLT2I

SGLT2I

DPP4I

TZD†

DPP4I

TZD†

Basal insulin†

AGI

Basal insulin†

DPP4I

TZD†

Colesevelam

Colesevelam

SU/glinide†

BCR-QR

BCR-QR

 

AGI

AGI

 

SU/glinide†

SU/glinide†

AGI = -glucosidase inhibitors; BCR-QR = bromocriptine quick release; Coles = colesevelam; DPP4I = dipeptidyl peptidase 4 inhibitors;
GLP1RA = glucagon-like peptide 1 receptor agonists; Met = metformin; SGLT2I = sodium-glucose cotransporter 2 inhibitors; SU =
sulfonylureas; TZD = thiazolidinediones.
*Intensify therapy whenever A1C exceeds individualized target. Boldface denotes little or no risk of hypoglycemia or weight gain, few
adverse events, and/or the possibility of benefits beyond glucose-lowering.
†

Use with caution.

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Basal Insulin Analogs
• Doesn’t have to be permanent.
• Safe and effective.
• But overly aggressive  hypoglycemia.

• Hypoglycemia
• Cognitive & psychological changes.
• Accidents & falls.
• CV Effects.

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Pharmacokinetics of Insulin
Onset
(h)

Peak (h)

Duration
(h)

NPH

2-4

4-10

10-16

Ba
sal Glargine
Detemir

~1-4

No pronounced
peak*

Up to 24†

Ba Regular U-500
sal
Pr
an
dia
l

≤0.5

~2-3

12-24

Pr Regular
an
dia
l
Aspart
Glulisine
Lispro
Inhaled insulin

~0.5-1

~2-3

Up to 8




Must be injected 30-45 min before a meal
Injection with or after a meal could increase
risk for hypoglycemia

<0.5

~0.5-2.5

~3-5




Can be administered 0-15 min before a meal
Less risk of postprandial hypoglycemia
compared to regular insulin 

Agent

Considerations
Greater risk of nocturnal hypoglycemia compared
to insulin analogs
Less nocturnal hypoglycemia compared to NPH




Inject 30 min before a meal
Indicated for highly insulin resistant
individuals
Use caution when measuring dosage to avoid
inadvertent overdose

* Exhibits a peak at higher dosages.
† Dose-dependent.
NPH, Neutral Protamine Hagedorn.
Moghissi E et al. Endocr Pract. 2013;19:526-535. Humulin R U-500 (concentrated) insulin prescribing information. Indianapolis: Lilly USA, LLC.

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Case Discussion 1

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Case Discussion 2
• 48-year old Hispanic woman comes to her doctor for
recommendations about her weight. She is married, has
2 children in school and works full time as a bookkeeper.
She eats breakfast and dinner at home, and buys lunch
at various locations.

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Case Discussion 3
• John is a 55 year-old Caucasian man with diabetes
and asthma. He teaches math at a local high school
in New York City. He was diagnosed with type 2
diabetes on blood tests performed when he applied
for life insurance at age 51. At the time, he was
obese, weighing 220 pounds at 5 feet, 10 inches
height (BMI = 31.6). With HbA1c level of 7.2%.

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References
• Management of hyperglycemia in type 2 diabetes: a
patient-centered approach; Diabetes care, volume
35,pg1364-1380; Silvio E.Inzucchi
• Patient case discussions in TD: what intensification plan
is best?;Medscape education; Luingi F.Meneghini.

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