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

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

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

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.

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.

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.

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

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

11

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
Diaeta, 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

Doesnt 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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