DIABETES

MANAGEMENT UPDATE
2016 March

Criteria for the Diagnosis of Diabetes

A1C 6.5%
OR

Fasting plasma glucose (FPG)

126 mg/dL (7.0 mmol/L)
OR

2-h plasma glucose 200 mg/dL

(11.1 mmol/L) during an OGTT
OR

A random plasma glucose 200 mg/dL

(11.1 mmol/L) if symptoms present
ADA. 2. Classification and Diagnosis. Diabetes Care 2015;38(suppl 1):S9; Table 2.1

Categories of Increased Risk for Diabetes

(Prediabetes)*
FPG 100125 mg/dL (5.66.9 mmol/L): IFG
OR

2-h plasma glucose in the 75-g OGTT

140199 mg/dL (7.811.0 mmol/L): IGT
OR

A1C 5.76.4%

*For all three tests, risk is continuous, extending below the lower limit of a range and becoming
disproportionately greater at higher ends of the range.

ADA. 2. Classification and Diagnosis. Diabetes Care 2015;38(suppl 1):S10; Table 2.3

Testing should begin at age 45 for all

patients, particularly those who are
overweight or obese. B

Consider testing for prediabetes in

asymptomatic adults of any age w/ BMI
25 kg/m2 or 23 kg/m2 (in Asian
Americans) who have 1 or more addl risk
factors for diabetes. B

If tests are normal, repeat at a minimum

of 3-year intervals. C

Patients with prediabetes should be

referred to an intensive diet and physical
activity behavioral counseling program
adhering to the tenets of the DPP
targeting a loss of 7% of body weight,
and should increase their moderate
physical activity to at least 150
min/week. A

Offer follow-up counseling and

maintenance programs for long-term
success in preventing diabetes. B

Metformin therapy for prevention of type

2 diabetes should be considered in those
with prediabetes, especially for those
with BMI >35 kg/m2, aged < 60 years,
and women with prior gestational
diabetes (GDM). A

Body Mass Index Category (kg/m2)

Treatment
Diet,
physical activity &
behavioral therapy
Pharmacotherapy

Bariatric surgery

23.0* or
25.0-26.9

27.0-29.9

30.0-34.9

35.0-39.9

40

Primary prevention

Evidence support that healthy diet and

exercise prevent diabetes
Diet different strategies to educate about
healthydiet food pyramid , food rainbow,
food plate method
Exercise- aerobic 150 min/week and
anaerobic 3sessins per week
Exercise according to the person.
Sedentary person walking speed 3.2 km/hr

Impact of Intensive Therapy

for Diabetes: Summary of
Major Clinical Trials
Study
UKPDS
DCCT /
EDIC*
ACCORD
ADVANCE
VADT

Microva
sc

CVD

KendallDM,BergenstalRM.InternationalDiabetesCenter2009

UKProspectiveDiabetesStudy(UKPDS)Group.Lancet1998;352:854.

Mortality

Initial Trial

Long Term Follow

up
* in T1DM

Legacy effect and metabolic

memory

short clinical trials, more intensive glucose

control has an overall neutral effect on
cardiovascular events. In longer term followup investigations, however, a statistically
significant beneficial effect eventually
emerged in both the DCCT (Type 1) and the
UKPDS (Type 2.) Some have therefore
proposed that there may be a legacy effect
from previous tight glycemic control on these
macrovascular outcomes something that
may not be appreciated for several decades

Multiple, Complex
Pathophysiological
Abnormalities
in
T2DM
GLP-1R
Insulin
pancreatic
agonists

incretin
effect

Glinides

DPP-4
inhibitors

Amylin
mimetics
_

gut A G I s
carbohydrate
delivery &
absorption

SUs

insulin
secretion

pancreatic
glucagon
secretion DA

agonists

HYPERGLYCEMIA

Metformin

TZDs

Bile acid
sequestrants

hepatic
glucose
production

renal
glucose
excretion

peripheral
glucose
uptake

Adapted from: Inzucchi SE, Sherwin RS in: Cecil Medicine 2011

Components of the Comprehensive

Diabetes Evaluation (1)
Medical history (1)

Age and characteristics of onset of diabetes (e.g.,

DKA, asymptomatic laboratory finding

Eating patterns, physical activity habits, nutritional

status, and weight history; growth and development
in children and adolescents

Diabetes education history

Review of previous treatment regimens and response

to therapy (A1C records)

ADA. 3. Initial Evaluation and Diabetes Management Planning. Diabetes Care 2015;38(suppl 1):S18

Components of the Comprehensive

Diabetes Evaluation (2)
Medical history (2)

Current treatment of diabetes, including medications,

adherence and barriers thereto, meal plan, physical
activity patterns, readiness for behavior change

Results of glucose monitoring, patients use of data

DKA frequency, severity, cause

Hypoglycemic episodes

Hypoglycemic awareness
Any severe hypoglycemia: frequency, cause

ADA. 3. Initial Evaluation and Diabetes Management Planning. Diabetes Care 2015;38(suppl 1):S18

Components of the
Comprehensive Diabetes
Evaluation (3)

Medical history (3)

History of diabetes-related complications

Microvascular: retinopathy, nephropathy, neuropathy

Sensory neuropathy, including history of foot lesions
Autonomic neuropathy, including sexual dysfunction and
gastroparesis

Macrovascular: CHD, cerebrovascular disease, PAD

Other: psychosocial problems,* dental disease*

*See appropriate referrals for these categories.

ADA. 3. Initial Evaluation and Diabetes Management Planning. Diabetes Care 2015;38(suppl 1):S18

3. ANTI-HYPERGLYCEMIC THERAPY

Glycemic targets
-

HbA1c < 7.0% (mean PG 150-160 mg/dl [8.38.9 mmol/l])

Pre-prandial PG <130 mg/dl (7.2 mmol/l)

Post-prandial PG <180 mg/dl (10.0 mmol/l)

Individualization is key:

Tighter targets (6.0 - 6.5%) - younger,

healthier
Looser targets (7.5 - 8.0%+) - older,
PG = plasma glucose
comorbidities,

Diabetes Care 2012;35:13641379; Diabetologia 2012;55:15771596

hypoglycemia
prone,Diabetologia2015;58:429-442
etc.
Diabetes Care 2015;38:140-149;

Figure 1. Modulation of
the intensiveness of
glucose lowering
therapy in T2DM
PATIENT / DISEASE FEATURES

Approach to the management

of hyperglycemia
HbA1c

more
stringent

7%

Risks potentially associated

low
with hypoglycemia and
other drug adverse effects
Disease duration

Life expectancy

Important comorbidities

Established vascular
complications

Patient attitude and

expected treatment efforts

Resources and support

system

less
stringent
high

newly diagnosed

long-standing

Usually not
modifable
long

short

absent

few / mild

severe

absent

few / mild

severe

highly motivated, adherent,

excellent self-care capacities

Readily available

less motivated, non-adherent,

poor self-care capacities

Potentially
modifable

limited

DiabetesCare2015;38:140149;Diabetologia 2015;58:429-442

Healthy eating, weight control, increased physical activity & diabetes education

Monotherapy

Metformin

Efcacy*
Hypo risk
Weight
Side effects
Costs

high
low risk
neutral/loss
GI / lactic acidosis
low
If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):

Dual
therapy
Efcacy*
Hypo risk
Weight
Side effects
Costs

Metformin

Metformin

Sulfonylurea

Thiazolidinedione

DPP-4
inhibitor

high
moderate risk
gain
hypoglycemia
low

high
low risk
gain
edema, HF, fxs
low

intermediate
low risk
neutral
rare
high

Metformin

Metformin

Metformin

Metformin

SGLT2
inhibitor

GLP-1 receptor
agonist

Insulin (basal)

intermediate
low risk
loss
GU, dehydration
high

high
low risk
loss
GI
high

highest
high risk
gain
hypoglycemia
variable

If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):

Metformin

Triple
therapy

Sulfonylurea

+
TZD

Metformin

Thiazolidinedione

SU

Metformin

Metformin

DPP-4
Inhibitor

SGLT-2
Inhibitor

SU

SU

Metformin

GLP-1 receptor
agonist

Metformin

Insulin (basal)

+
TZD

SU

or

DPP-4-i

or

DPP-4-i

or

TZD

or

TZD

or

TZD

or

DPP-4-i

or

SGLT2-i

or

SGLT2-i

or

SGLT2-i

or

DPP-4-i

or

Insulin

or

SGLT2-i

or

Insulin

or

Insulin

or GLP-1-RA

or GLP-1-RA

or

or

Insulin

or GLP-1-RA

Insulin

If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add
basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGL T2-i:

Metformin

Combination
Figure
2. Anti-hyperglycemic
Basal Insulin +
injectable

therapy
therapy
in T2DM: General

Mealtime Insulin or

GLP-1-RA

DiabetesCare2015;38:140149;Diabetologia 2015;58:429-442

Healthy eating, weight control, increased physical activity & diabetes education

Monotherapy

Metformin

Efcacy*
Hypo risk
Weight
Side effects
Costs

high
low risk
neutral/loss
GI / lactic acidosis
low
If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):

Dual
therapy
Efcacy*
Hypo risk
Weight
Side effects
Costs

Metformin

Metformin

Sulfonylurea

Thiazolidinedione

DPP-4
inhibitor

high
moderate risk
gain
hypoglycemia
low

high
low risk
gain
edema, HF, fxs
low

intermediate
low risk
neutral
rare
high

Metformin

Metformin

Metformin

Metformin

SGLT2
inhibitor

GLP-1 receptor
agonist

Insulin (basal)

intermediate
low risk
loss
GU, dehydration
high

high
low risk
loss
GI
high

highest
high risk
gain
hypoglycemia
variable

If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):

Metformin

Triple
therapy

Sulfonylurea

+
TZD

Metformin

Thiazolidinedione

SU

Metformin

Metformin

DPP-4
Inhibitor

SGLT-2
Inhibitor

SU

SU

Metformin

GLP-1 receptor
agonist

Metformin

Insulin (basal)

+
TZD

SU

or

DPP-4-i

or

DPP-4-i

or

TZD

or

TZD

or

TZD

or

DPP-4-i

or

SGLT2-i

or

SGLT2-i

or

SGLT2-i

or

DPP-4-i

or

Insulin

or

SGLT2-i

or

Insulin

or

Insulin

or GLP-1-RA

or GLP-1-RA

or

or

Insulin

or GLP-1-RA

Insulin

If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add
basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGL T2-i:

Metformin

Combination
Figure
2. Anti-hyperglycemic
Basal Insulin +
injectable

therapy
therapy
in T2DM: General

Mealtime Insulin or

GLP-1-RA

DiabetesCare2015;38:140149;Diabetologia 2015;58:429-442

Healthy eating, weight control, increased physical activity & diabetes education

Monotherapy

Metformin

Efcacy*
Hypo risk
Weight
Side effects
Costs

high
low risk
neutral/loss
GI / lactic acidosis
low
If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):

Dual
therapy
Efcacy*
Hypo risk
Weight
Side effects
Costs

Metformin

Metformin

Sulfonylurea

Thiazolidinedione

DPP-4
inhibitor

high
moderate risk
gain
hypoglycemia
low

high
low risk
gain
edema, HF, fxs
low

intermediate
low risk
neutral
rare
high

Metformin

Metformin

Metformin

Metformin

SGLT2
inhibitor

GLP-1 receptor
agonist

Insulin (basal)

intermediate
low risk
loss
GU, dehydration
high

high
low risk
loss
GI
high

highest
high risk
gain
hypoglycemia
variable

If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):

Metformin

Triple
therapy

Sulfonylurea

+
TZD

Metformin

Thiazolidinedione

SU

Metformin

Metformin

DPP-4
Inhibitor

SGLT-2
Inhibitor

SU

SU

Metformin

GLP-1 receptor
agonist

Metformin

Insulin (basal)

+
TZD

SU

or

DPP-4-i

or

DPP-4-i

or

TZD

or

TZD

or

TZD

or

DPP-4-i

or

SGLT2-i

or

SGLT2-i

or

SGLT2-i

or

DPP-4-i

or

Insulin

or

SGLT2-i

or

Insulin

or

Insulin

or GLP-1-RA

or GLP-1-RA

or

or

Insulin

or GLP-1-RA

Insulin

If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add
basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGL T2-i:

Metformin

Combination
Figure
2. Anti-hyperglycemic
Basal Insulin +
injectable

therapy
therapy
in T2DM: General

Mealtime Insulin or

GLP-1-RA

DiabetesCare2015;38:140149;Diabetologia 2015;58:429-442

Healthy eating, weight control, increased physical activity & diabetes education

Monotherapy

Metformin

Efcacy*
Hypo risk
Weight
Side effects
Costs

high
low risk
neutral/loss
GI / lactic acidosis
low
If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):

Dual
therapy
Efcacy*
Hypo risk
Weight
Side effects
Costs

Metformin

Metformin

Sulfonylurea

Thiazolidinedione

DPP-4
inhibitor

high
moderate risk
gain
hypoglycemia
low

high
low risk
gain
edema, HF, fxs
low

intermediate
low risk
neutral
rare
high

Metformin

Metformin

Metformin

Metformin

SGLT2
inhibitor

GLP-1 receptor
agonist

Insulin (basal)

intermediate
low risk
loss
GU, dehydration
high

high
low risk
loss
GI
high

highest
high risk
gain
hypoglycemia
variable

If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):

Metformin

Triple
therapy

Sulfonylurea

+
TZD

Metformin

Thiazolidinedione

SU

Metformin

Metformin

DPP-4
Inhibitor

SGLT-2
Inhibitor

SU

SU

Metformin

GLP-1 receptor
agonist

Metformin

Insulin (basal)

+
TZD

SU

or

DPP-4-i

or

DPP-4-i

or

TZD

or

TZD

or

TZD

or

DPP-4-i

or

SGLT2-i

or

SGLT2-i

or

SGLT2-i

or

DPP-4-i

or

Insulin

or

SGLT2-i

or

Insulin

or

Insulin

or GLP-1-RA

or GLP-1-RA

or

or

Insulin

or GLP-1-RA

Insulin

If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add
basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGL T2-i:

Metformin

Combination
injectable
therapy

Basal Insulin +

Mealtime Insulin or

GLP-1-RA

DiabetesCare2015;38:140149;Diabetologia 2015;58:429-442

Healthy eating, weight control, increased physical activity & diabetes education

Monotherapy

Metformin

Efcacy*
Hypo risk
Weight
Side effects
Costs

Metformin
intolerance
or
contraindic
Dual

therapy
ation
Efcacy*
HbA1
c
9%

Hypo risk
Weight
Side effects
Costs

high
low risk
neutral/loss
GI / lactic acidosis
low
If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):

Metformin

Metformin

Sulfonylurea

Thiazolidinedione

DPP-4
inhibitor

high
moderate risk
gain
hypoglycemia
low

high
low risk
gain
edema, HF, fxs
low

intermediate
low risk
neutral
rare
high

Sulfonylurea

+
TZD

Uncontrolled
hyperglycemi
a (catabolic
features,
BG 300-350
mg/dl, HbA1c
10-12%)
Combination
injectable
therapy

Metformin

Metformin

Metformin

Metformin

SGLT2
inhibitor

GLP-1 receptor
agonist

Insulin (basal)

intermediate
low risk
loss
GU, dehydration
high

high
low risk
loss
GI
high

highest
high risk
gain
hypoglycemia
variable

If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):

Metformin

Triple
therapy

Metformin

Thiazolidinedione

SU

Metformin

Metformin

DPP-4
Inhibitor

SGLT-2
Inhibitor

SU

SU

Metformin

GLP-1 receptor
agonist

Metformin

Insulin (basal)

+
TZD

SU

or

DPP-4-i

or

DPP-4-i

or

TZD

or

TZD

or

TZD

or

DPP-4-i

or

SGLT2-i

or

SGLT2-i

or

SGLT2-i

or

DPP-4-i

or

Insulin

or

SGLT2-i

or

Insulin

or

Insulin

or GLP-1-RA

or GLP-1-RA

or

or

Insulin

or GLP-1-RA

Insulin

If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add
basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGL T2-i:

Metformin

Basal Insulin +

Mealtime Insulin or

GLP-1-RA

DiabetesCare2015;38:140149;Diabetologia 2015;58:429-442

Healthy eating, weight control, increased physical activity & diabetes education

Monotherapy

Metformin

Efcacy*
Hypo risk
Weight
Side effects
Costs

high
low risk
neutral/loss
GI / lactic acidosis
low
If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):

Dual
therapy
Efcacy*
Hypo risk
Weight
Side effects
Costs

Metformin

Metformin

Sulfonylurea

Thiazolidinedione

DPP-4
inhibitor

high
moderate risk
gain
hypoglycemia
low

high
low risk
gain
edema, HF, fxs
low

intermediate
low risk
neutral
rare
high

Metformin

Metformin

Metformin

Metformin

SGLT2
inhibitor

GLP-1 receptor
agonist

Insulin (basal)

intermediate
low risk
loss
GU, dehydration
high

high
low risk
loss
GI
high

highest
high risk
gain
hypoglycemia
variable

If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):

Metformin

Triple
therapy

Sulfonylurea

+
TZD

Metformin

Thiazolidinedione

SU

Metformin

Metformin

DPP-4
Inhibitor

SGLT-2
Inhibitor

SU

SU

Metformin

GLP-1 receptor
agonist

Metformin

Insulin (basal)

+
TZD

SU

or

DPP-4-i

or

DPP-4-i

or

TZD

or

TZD

or

TZD

or

DPP-4-i

or

SGLT2-i

or

SGLT2-i

or

SGLT2-i

or

DPP-4-i

or

Insulin

or

SGLT2-i

or

Insulin

or

Insulin

or GLP-1-RA

or GLP-1-RA

or

or

Insulin

or GLP-1-RA

Insulin

If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add
basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGL T2-i:

Figure 2A. AntiCombination

hyperglycemic
therapy
injectable

therapy
in T2DM:

Metformin

Basal Insulin +

Mealtime Insulin or

GLP-1-RA

DiabetesCare2015;38:140149;Diabetologia 2015;58:429-442

Healthy eating, weight control, increased physical activity & diabetes education

Monotherapy

Metformin

Efcacy*
Hypo risk
Weight
Side effects
Costs

high
low risk
neutral/loss
GI / lactic acidosis
low
If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):

Dual
therapy
Efcacy*
Hypo risk
Weight
Side effects
Costs

Metformin

Metformin

Sulfonylurea

Thiazolidinedione

DPP-4
inhibitor

high
moderate risk
gain
hypoglycemia
low

high
low risk
gain
edema, HF, fxs
low

intermediate
low risk
neutral
rare
high

Metformin

Metformin

Metformin

Metformin

SGLT2
inhibitor

GLP-1 receptor
agonist

Insulin (basal)

intermediate
low risk
loss
GU, dehydration
high

high
low risk
loss
GI
high

highest
high risk
gain
hypoglycemia
variable

If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):

Metformin

Triple
therapy

Sulfonylurea

+
TZD

Metformin

Thiazolidinedione

SU

Metformin

Metformin

DPP-4
Inhibitor

SGLT-2
Inhibitor

SU

SU

Metformin

GLP-1 receptor
agonist

Metformin

Insulin (basal)

+
TZD

SU

or

DPP-4-i

or

DPP-4-i

or

TZD

or

TZD

or

TZD

or

DPP-4-i

or

SGLT2-i

or

SGLT2-i

or

SGLT2-i

or

DPP-4-i

or

Insulin

or

SGLT2-i

or

Insulin

or

Insulin

or GLP-1-RA

or GLP-1-RA

or

or

Insulin

or GLP-1-RA

Insulin

If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add
basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGL T2-i:

Figure 2B. AntiCombination

hyperglycemic
therapy
injectable

therapy
in T2DM:

Metformin

Basal Insulin +

Mealtime Insulin or

GLP-1-RA

DiabetesCare2015;38:140149;Diabetologia 2015;58:429-442

Healthy eating, weight control, increased physical activity & diabetes education

Monotherapy

Metformin

Efcacy*
Hypo risk
Weight
Side effects
Costs

high
low risk
neutral/loss
GI / lactic acidosis
low
If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):

Dual
therapy
Efcacy*
Hypo risk
Weight
Side effects
Costs

Metformin

Metformin

Sulfonylurea

Thiazolidinedione

DPP-4
inhibitor

high
moderate risk
gain
hypoglycemia
low

high
low risk
gain
edema, HF, fxs
low

intermediate
low risk
neutral
rare
high

Metformin

Metformin

Metformin

Metformin

SGLT2
inhibitor

GLP-1 receptor
agonist

Insulin (basal)

intermediate
low risk
loss
GU, dehydration
high

high
low risk
loss
GI
high

highest
high risk
gain
hypoglycemia
variable

If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):

Metformin

Triple
therapy

Sulfonylurea

+
TZD

Metformin

Thiazolidinedione

SU

Metformin

Metformin

DPP-4
Inhibitor

SGLT-2
Inhibitor

SU

SU

Metformin

GLP-1 receptor
agonist

Metformin

Insulin (basal)

+
TZD

SU

or

DPP-4-i

or

DPP-4-i

or

TZD

or

TZD

or

TZD

or

DPP-4-i

or

SGLT2-i

or

SGLT2-i

or

SGLT2-i

or

DPP-4-i

or

Insulin

or

SGLT2-i

or

Insulin

or

Insulin

or GLP-1-RA

or GLP-1-RA

or

or

Insulin

or GLP-1-RA

Insulin

If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add
basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGL T2-i:

Figure 2C. AntiCombination

hyperglycemic
injectable

therapy
therapy
in T2DM:

Metformin

Basal Insulin +

Mealtime Insulin or

GLP-1-RA

DiabetesCare2015;38:140149;Diabetologia 2015;58:429-442

each new class of noninsulin agents

added to initial therapy lowers A1C
around 0.91.1%

So initial HbA1C is important in deciding

treatment strategy

If FPG> 200 start with 2 drugs

If FPG> 300 with insulin or 3 drugs

Update:
Management of Hyperglycemia in
T2DM, 2015

3. ANTI-HYPERGLYCEMIC THERAPY

Therapeutic options: Insulins

Human Insulins
- Neutral protamine Hagedorn (NPH)
- Regular human insulin
- Pre-mixed formulations
Insulin Analogues
- Basal analogues (glargine, detemir,
degludec)
- Rapid analogues (lispro, aspart, glulisine)
Diabetes Care 2012;35:13641379; Diabetologia 2012;55:15771596
- Pre-mixed formulations
Diabetes Care 2015;38:140-149; Diabetologia2015;58:429-442

Update:
Management of Hyperglycemia in
T2DM, 2015

3. ANTI-HYPERGLYCEMIC THERAPY

Insulin level

Therapeutic options: Insulins

Rapid (Lispro, Aspart, Glulisine)
Short (Regular)

Long (Detemir)

(Degludec)

Long (Glargine)
0
20

2
22

Hours

4
6
8
10
12
14
24 Hours after injection

16

18

Figure
3.
Approac
h to
starting
&
adjustin
g
insulin
in T2DM

Diabetes Care 2015;38:140-149;

Diabetologia 2015;58:429-442

Basal Insulin
(usually with metformin +/other non-insulin agent)

Start: 10U/day or 0.1-0.2 U/kg/day

Adjust: 10-15% or 2-4 U once-twice weekly to
reach FBG target.
For hypo: Determine & address cause;
dose by 4 units or 10-20%.

Figure
3.
Approac
h to
starting
&
adjustin
g
insulin
in T2DM

Basal Insulin
(usually with metformin +/other non-insulin agent)

Start: 10U/day or 0.1-0.2 U/kg/day

Adjust: 10-15% or 2-4 U once-twice weekly to
reach FBG target.
For hypo: Determine & address cause;
dose by 4 units or 10-20%.

Add 1 rapid insulin* injections

before largest meal

If not
controlled after
FBG target is reached
(or if dose > 0.5 U/kg/ day),
treat PPG excursions with
meal-time insulin.
(Consider initial
GLP-1-RA
trial.)

Change to
premixed insulin* twice daily

Start: 4U, 0.1 U/kg, or 10% basal dose. If

A1c<8%, consider basal by same amount.

Start: Divide current basal dose into 2/3 AM,

1/3 PM or 1/2 AM, 1/2 PM.

Adjust: dose by 1-2 U or 10-15% oncetwice weekly until SMBG target reached.

Adjust: dose by 1-2 U or 10-15% oncetwice weekly until SMBG target reached.

For hypo: Determine and address cause;

corresponding dose by 2-4 U or 10-20%.

For hypo: Determine and address cause;

corresponding dose by 2-4 U or 10-20%.

If not
controlled,
consider basalbolus.

Add 2 rapid insulin* injections

before meals ('basal-bolus)
Start: 4U, 0.1 U/kg, or 10% basal dose/meal. If
A1c<8%, consider basal by same amount.
Adjust: dose by 1-2 U or 10-15% once-twice
weekly to achieve SMBG target.
For hypo: Determine and address cause;
corresponding dose by 2-4 U or 10-20%.

Diabetes Care 2015;38:140-149;

Diabetologia 2015;58:429-442

If not
controlled,
consider basalbolus.

Figure Inject#ions
3.
1
Approac
h to
starting
&
adjustin
g
insulin
in T2DM
2

3+

Complexity

Basal Insulin

low

(usually with metformin +/other non-insulin agent)

Start: 10U/day or 0.1-0.2 U/kg/day

Adjust: 10-15% or 2-4 U once-twice weekly to
reach FBG target.
For hypo: Determine & address cause;
dose by 4 units or 10-20%.

Add 1 rapid insulin* injections

before largest meal

If not
controlled after
FBG target is reached
(or if dose > 0.5 U/kg/ day),
treat PPG excursions with
meal-time insulin.
(Consider initial
GLP-1-RA
trial.)

Change to
premixed insulin* twice daily

Start: 4U, 0.1 U/kg, or 10% basal dose. If

A1c<8%, consider basal by same amount.

Start: Divide current basal dose into 2/3 AM,

1/3 PM or 1/2 AM, 1/2 PM.

Adjust: dose by 1-2 U or 10-15% oncetwice weekly until SMBG target reached.

Adjust: dose by 1-2 U or 10-15% oncetwice weekly until SMBG target reached.

For hypo: Determine and address cause;

corresponding dose by 2-4 U or 10-20%.

For hypo: Determine and address cause;

corresponding dose by 2-4 U or 10-20%.

If not
controlled,
consider basalbolus.

Add 2 rapid insulin* injections

before meals ('basal-bolus)

If not
controlled,
consider basalbolus.

Start: 4U, 0.1 U/kg, or 10% basal dose/meal. If

A1c<8%, consider basal by same amount.
Adjust: dose by 1-2 U or 10-15% once-twice
weekly to achieve SMBG target.
For hypo: Determine and address cause;
corresponding dose by 2-4 U or 10-20%.

Diabetes Care 2015;38:140-149;

Diabetologia 2015;58:429-442

Flexibility

more fexible

less fexible

mod.

high

Basal vs Bolus Insulin

BASAL INSULIN

9/25/16

Suppress hepatic
glucose production
(overnight and
intermeal)
Prevent catabolism
(lipid and protein)
Ketosis
Unregulated amino
acid release
Reduce
glucolipotoxicity

BOLUS INSULIN

Meal-associated
CHO disposal
Storage of nutrients
Help suppress intermeal hepatic
glucose production
31

Analog Insulin Profles

Aspart, Lispro, Glulisine (45 hr)
Regular (610 hr)
Plasma Insulin Levels

NPH (1020 hr)

Ultralente (~1620 hr )
Detemir
~18hr

0
9/25/16

10

12

Glargine (~24 hr)

14

Time (hr)

16

18

20

22

24

Rosenstock J. Clin Cornerstone. 32

2001;4:50-61.

Natural History of Type 2

Diabetes

Postme
al
glucose

Plasma
Glucos
e

Fasting
glucose

126 mg/dL

Insulin resistance

Relative Cell
Function

Insulin secretion

20

10

10

20

30

Years of
Diabetes
Adapted from International Diabetes Center (IDC). Minneapolis,
Minnesota.
9/25/16

33

Evolution of Treatment
Strategies
Pre-1995

Diagnosi
s
SU
Stop SU
Insulin

9/25/16

2000

Diagnosi
s
Monothera
py
Dual/Trip
le
Therapy
Stop
OHA
Insulin

Current

Diagnosi
s
Dual
Monothera
Therapy
py
Basal
Insulin +
OHA

Triple
Therapy
Stop SU

Prandial and
Basal Insulin +

34

Components of the
Comprehensive Diabetes
Evaluation

Referrals

Eye care professional for annual dilated eye exam

Family planning for women of reproductive age

Registered dietitian for MNT

Diabetes self-management education/support

Dentist for comprehensive periodontal examination

Mental health professional, if needed

ADA. 3. Initial Evaluation and Diabetes Management Planning. Diabetes Care 2015;38(suppl 1):S18

Recommendation: Assessment of
Common Comorbid Conditions

Consider assessing for and addressing

common comorbid conditions that may
complicate the management of diabetes
B
Common comorbidities
Depression
Cognitive impairment
Obstructive sleep apnea

Low testosterone in men

Fatty liver disease

Periodontal disease

Cancer

Hearing impairment

Fractures

ADA. 3. Initial Evaluation and Diabetes Management Planning. Diabetes Care 2015;38(suppl 1):S17

Recommendation:
Macronutrient Distribution

Evidence suggests there is no ideal

percentage of calories from carbohydrate,
protein, and fat for all people with diabetes
B
Therefore, macronutrient distribution should
be based on individualized assessment of
current eating patterns, preferences, and
metabolic goals E

ADA. 4. Foundations of Care. Diabetes Care 2015;38(suppl 1):S22

Recommendations: Physical Activity

Children with diabetes/prediabetes: engage in at

least 60 min/day physical activity B
Adults with diabetes: at least 150 min/wk of
moderate-intensity aerobic activity
(5070% of maximum heart rate),over at least 3
days/wk with no more than 2 consecutive days
without exercise A
Evidence supports that all individuals, including
those with diabetes, should be encouraged to reduce
sedentary time, particularly by breaking up extended
amoungs of time (>90 min) spent sitting B
If not contraindicated, adults with type 2 diabetes
should perform resistance training at least twice
weekly A

ADA. 4. Foundations of Care. Diabetes Care 2015;38(suppl 1):S24

Smoking
cessation
Good
psychological
support

Recommendations: A1C

Perform the A1C test at least two times a year in

patients meeting treatment goals (and have stable
glycemic control) E
Perform the A1C test quarterly in patients whose
therapy has changed or who are not meeting
glycemic goals E
Use of point-of-care (POC) testing for A1C provides
the opportunity for more timely treatment changes E
glycemic control is best judged by the combination
of result of self-monitoring of blood glucose
(SMBG) testing and A1C

ADA. 6. Glycemic Targets. Diabetes Care 2015;38(suppl 1):S34

Glycemic Recommendations for

Nonpregnant Adults with Diabetes
A1C

<7.0%*

Preprandial capillary
plasma glucose

80130 mg/dL*
(4.47.2 mmol/L)

Peak postprandial
<180 mg/dL*
capillary plasma glucose (<10.0 mmol/L)

*Goals should be individualized.

Postprandial glucose measurements should be made 12 h after the beginning of the meal, generally
peak levels in patients with diabetes.
ADA. 6. Glycemic Targets. Diabetes Care 2015;38(suppl 1):S37; Table 6.2

Recommendations: Bariatric Surgery

Bariatric surgery may be considered for

adults with BMI > 35 kg/m2 and type 2
diabetes, especially if diabetes or associated
comorbidities are difficult to control with
lifestyle and pharmacological therapy B
After surgery, life-long lifestyle support and
medical monitoring is necessary B
Insufficient evidence to recommend surgery
in patients with BMI <35 kg/m2 outside of a
research protocol E

ADA. 7. Approaches to Glycemic Treatment. Diabetes Care 2015;38(suppl 1):S46

Recommendations:
Hypertension/Blood Pressure Control
Goals

People with diabetes and hypertension should be treated

to a systolic blood pressure goal of <140 mmHg A

Lower systolic targets, such as <130 mmHg, may be

appropriate for certain individuals, such as younger
patients, if it can be achieved without undue treatment
burden C

Patients with diabetes should be treated to a diastolic

blood pressure <90 mmHg A

Lower diastolic targets, such as <80 mmHg, may be

appropriate for certain individuals, such as younger
patients, if it can be achieved without undue treatment
burden B

ADA. 8. Cardiovascular Disease and Risk Management. Diabetes Care 2015;38(suppl 1):S49

Recommendations:
Hypertension/Blood Pressure Control
Treatment (3)

Pharmacological therapy for patients with

diabetes and hypertension comprise a regimen
that includes

either an ACE inhibitor or angiotensin II receptor blocker

B;
if one class is not tolerated, substitute the other C

Multiple drug therapy (two or more agents at

maximal doses) generally required to achieve
blood pressure targets B

ADA. 8. Cardiovascular Disease and Risk Management. Diabetes Care 2015;38(suppl 1):S50

Recommendations:
Hypertension/Blood Pressure Control
Treatment (4)

If ACE inhibitors, ARBs, or diuretics are used, serum

creatinine/eGFR and potassium levels should be
monitored E

In pregnant patients with diabetes and chronic

hypertension, blood pressure target goals of 110129/65
79 mmHg are suggested in interest of long-term maternal
health and minimizing impaired fetal growth; ACE
inhibitors, ARBs, contraindicated during pregnancy E

ADA. 8. Cardiovascular Disease and Risk Management. Diabetes Care 2015;38(suppl 1):S50

Recommendations for Statin

Treatment in People with Diabetes (4)
Age

Risk factors

<40 years

4075 years

>75 years

Recommended
statin dose*

None

None

CVD risk
factor(s)**

Moderate or
high

Overt CVD***

High

None

Moderate

CVD risk factors High

Overt CVD

High

None

Moderate

Moderate or
CVD risk factors
high
Overt CVD

High

Monitoring with
lipid panel
Annually or as
needed to
monitor for
adherence
As needed to
monitor
adherence
As needed to
monitor
adherence

* In addition to lifestyle therapy.

** CVD risk factors include LDL cholesterol 100 mg/dL (2.6 mmol/L), high blood pressure, smoking,
and
overweight and obesity.
*** Overt CVD includes those with previous cardiovascular events or acute coronary syndromes.
ADA. 8. Cardiovascular Disease and Risk Management. Diabetes Care 2015;38(suppl 1):S52, Table 8.1

Recommendations:
Dyslipidemia/Lipid Management (5)
Treatment recommendations and goals

In clinical practice, providers may need to adjust

intensity of statin therapy based on individual
patient response to medication (e.g. side
effects, tolerability, LDL cholesterol levels.) E

Cholesterol laboratory testing may be helpful in

monitoring adherence to therapy but may not
be needed once the patient is stable on therapy
E
Ezetimibe + moderate intensity statin therapy
provides addl CV benefit over moderate
intensity statin therapy alone; consider for
patients with a recent acute coronary syndrome
w/ LDL 50mg/dL or in patients who cant
tolerate high-intensity statin therapy. A

ADA. 8. Cardiovascular Disease and Risk Management. Diabetes Care 2015;38(suppl 1):S52

High- and ModerateIntensity Statin Therapy*

High Intensity
Statin Therapy

Moderate-Intensity
Statin Therapy

Lowers LDL by 50%

Lowers LDL by 30 - <50%

Atorvastatin 40-80 mg

Atorvastatin 10-20 mg

Rosuvastatin 20-40 mg

Rosuvastatin 5-10 mg
Simvastatin 20-40 mg
Pravastatin 40-80 mg
Lovastatin 40 mg
Fluvastatin XL 80 mg

* Once-daily dosing

Pitavastatin 2-4 mg

American Diabetes Association Standards of Medical Care in Diabetes. Cardiovascular

disease and risk management. Diabetes Care 2016; 39 (Suppl. 1): S60-S71

Recommendations:
Antiplatelet Agents
Consider aspirin therapy (75162 mg/day) C
As

a primary prevention strategy in those with type

1 or type 2 diabetes at increased cardiovascular risk
(10-year risk >10%)
Includes

most men or women with diabetes age

50 years who have at least one additional major
risk factor, including:

Family history of premature ASCVD

Hypertension

Smoking

Dyslipidemia

Albuminuria
American Diabetes Association Standards of Medical Care in Diabetes. Cardiovascular
disease and risk management. Diabetes Care 2016; 39 (Suppl. 1): S60-S71

Recommendations:
Nephropathy (1)
Screening

At least once a year, quantitatively assess

urine albumin excretion and estimated
glomerular filtration rate B
In patients with type 1 diabetes duration of 5
years
In all patients with type 2 diabetes

ADA. 9. Microvascular Complications and Foot Care. Diabetes Care 2015;38(suppl 1):S58

Management of CKD in Diabetes (2)

GFR
30-44

Recommended
Monitor eGFR every 3 months
Monitor electrolytes, bicarbonate,
calcium, phosphorus, parathyroid
hormone, hemoglobin, albumin
weight every 36 months
Consider need for dose adjustment of
medications

<30

Referral to a nephrologist

ADA. 9.Microvascular Complications and Foot Care. Diabetes Care 2015;38(suppl 1):S60; Table 93;
Adapted from http://www.kidney.org/professionals/KDOQI/guideline_diabetes/

Recommendations:
Diabetes in Pregnancy (1)

Provide preconception counseling that addresses the

importance of tight control in reducing the risk of
congenital anomalies with an emphasis on achieving
A1C < 7%, if this can be achieved without
hypoglycemia. B
Potentially teratogenic medications (ACE inhibitors,
statins, etc.) should be avoided in sexually active
women of childbearing age who are not using
reliable contraception. B
GDM should be managed first with diet and exercise,
and medications should be added if needed. A

ADA. 12. Management of Diabetes in Pregnancy. Diabetes Care 2015;38(suppl 1):S77

Recommendations:
Diabetic
Retinopathy
(2)
Screening:
Initial

dilated and comprehensive eye

examination by an ophthalmologist or
optometrist:

Adults with type 1 diabetes, within 5 years of

diabetes onset. B

Patients with type 2 diabetes at the time of

diabetes diagnosis. B

American Diabetes Association Standards of Medical Care in Diabetes. Microvascular

complications and foot care. Diabetes Care 2016; 39 (Suppl. 1): S72-S80

Recommendations:
Diabetic
Screening (2): Retinopathy (3)
If

no evidence of retinopathy for one or more eye

exam, exams every 2 years may be considered. B
If

diabetic retinopathy if present subsequent

examinations for type 1 and type 2 diabetic patients
should be repeated annually by an ophthalmologist
or optometrist. B
If

retinopathy is progressing or sight-threatening,

more frequent exams
required. B

American Diabetes Association Standards of Medical Care in Diabetes. Microvascular

complications and foot care. Diabetes Care 2016; 39 (Suppl. 1): S72-S80

Recommendations:
Diabetic
Treatment (2): Retinopathy
Intravitreal

injections of VEGF are indicated for

center-involved diabetic macular edema, which
occurs beneath the foveal center and which may
threaten reading vision. A
Retinopathy

is not a contraindication to aspirin

therapy for cardioprotection, as it does not
increase the risk of retinal hemorrhage. A
Laser

treatment for high-risk PDR and, in some

cases, severe NPDR
American Diabetes Association Standards of Medical Care in Diabetes. Microvascular
complications and foot care. Diabetes Care 2016; 39 (Suppl. 1): S72-S80

Recommendations:
Neuropathy
Early recognition & management is
important because:
1.DN

is a diagnosis of exclusion.

2.Numerous
3.Up

treatment options exist.

to 50% of DPN may be asymptomatic.

4.Recognition

& treatment may improve

symptoms, reduce seqeullae, and improve
quality-of-life.

American Diabetes Association Standards of Medical Care in Diabetes. Microvascular

complications and foot care. Diabetes Care 2016; 39 (Suppl. 1): S72-S80

Recommendations: Neuropathy
(2)
Screening:
Assess

all patients for DPN at dx for T2DM, 5 years

after dx for T1DM, and at least annually thereafter.
B
Assessment

should include history & 10g

monofilament testing, and at least one of the
following: pinprick, temperature, and vibration
sensation. B
Symptoms

of autonomic neuropathy should be

assessed in patients with microvascular &
neuropathic complications. E
American Diabetes Association Standards of Medical Care in Diabetes. Microvascular
complications and foot care. Diabetes Care 2016; 39 (Suppl. 1): S72-S80

Recommendations: Neuropathy
(3)
Treatment:
Optimize

glucose control to prevent or delay

the development of neuropathy in patients
with T1DM A & to slow progression in
patients with T2DM. B
Assess

& treat patients to reduce pain

related to DPN B and symptoms of
autonomic neuropathy and to improve
quality of life. E

American Diabetes Association Standards of Medical Care in Diabetes. Microvascular

complications and foot care. Diabetes Care 2016; 39 (Suppl. 1): S72-S80

In ward management of
diabetes

Increase mortality with high BG levels in

ICU

Management of critically ill

In ward target 140-180

IV insulin is the best method
IV insulin algorithm started when above
180

Non critically ill

Total daily dose 0.5-0.7 U/kg/ day type 1

(TDD)
-0.5-1.0U/kg/day or more type 2

Basal - 50% of TDD

If isophane given as 2 doses
If long acting given at night
Bolus the remaining 50% given as short acting
insulins among 3 meals
Correction dose when pre meal glucose high
additional insulin given

Correction doses
1700 Rule (some modify this as the 1500 Rule
or the 1800 Rule)
1700/TDD = Expected amount of glucose
lowering per unit of insulin

9/25/16

No sliding scale

61

Example

70 kg patient type 2 DM having a CBS of

285mg/dl before lunch
TDD = 0.5 * 70 kg= 35 units

Basal bolus given at night = 18 units

During 3 meals = 6 unit tds.

Correction dose calculation 1500/35 = 40 mg/dl

by one unit of insulin.
So for correction (285- 130)/40 = 4 units given in
addition

Surgical patients

Elective postponed if HbA1C >9

Target 90-180 peri-operatively

Insulin infusions needed if

- major surgery
- type 1
- CBS >180 before surgery

IV rate = TDD/50 per hour

Others
Day before continue the routine DM
drugs/insulin
On the morning 50% of usual basal
dose requirement given
Then check every 2 hourly pre and during
surgery