AACE/ACE COMPREHENSIVE

DIABETES MANAGEMENT
ALGORITHM

2 015
TA S K FOR CE
Alan J. Garber, MD, PhD, FACE, Chair
Martin J. Abrahamson, MD

George Grunberger, MD, FACP, FACE

Joshua I. Barzilay, MD, FACE

Yehuda Handelsman, MD, FACP, FNLA, FACE

Lawrence Blonde, MD, FACP, FACE

Irl B. Hirsch, MD

Zachary T. Bloomgarden, MD, MACE

Paul S. Jellinger, MD, MACE

Michael A. Bush, MD

Janet B. McGill, MD, FACE

Samuel Dagogo-Jack, MD, DM, FRCP, FACE

Jeffrey I. Mechanick, MD, FACP, FACE, FACN, ECNU

Michael B. Davidson, DO, FACE

Paul D. Rosenblit, MD, PhD, FNLA, FACE

Daniel Einhorn, MD, FACP, FACE

Guillermo Umpierrez, MD, FACP, FACE

Jeffrey R. Garber, MD, FACP, FACE

Michael H. Davidson, MD, Advisor

W. Timothy Garvey, MD, FACE

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This material is protected by US copyright law. For permission to reused material in any format, complete a permission form
at www.aace.com/permissions. To purchase reprints of this article, please visit: www.aace.com/reprints. DOI:10.4158/EP15693.CS
Copyright 2015 AACE.

438 ENDOCRINE PRACTICE Vol 21 No. 4 April 2015

AACE/ACE Comprehensive Diabetes Management Algorithm, Endocr Pract. 2015;21(No. 4) 439

TA BL E OF CONTENTS
Compre he n sive Diabe t e s
A lg orit h m
I.

Complications-Centric
Model for Care of the
Overweight/Obese Patient

II.

Prediabetes Algorithm

III.

Goals of Glycemic Control

IV.

Glycemic Control Algorithm

V.

Algorithm for
Adding/Intensifying Insulin

VI.

CVD Risk Factor

Modifications Algorithm

VII.

Profiles of Antidiabetic
Medications

VIII. Principles for Treatment

of Type 2 Diabetes

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SELEC T:

STEP 3

Therapeutic targets for

improvement in complications

MEDIUM

Treatment
modality

Treatment intensity for weight

loss based on staging

HIGH

Lap band; gastric sleeve; gastric bypass

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If therapeutic targets for improvements in complications not met, intensify lifestyle and/or medical
and/or surgical treatment modalities for greater weight loss

Surgical Therapy (BMI 35):

phentermine; orlistat; lorcaserin; phentermine/topiramate ER;

naltrexone/bupropion; liraglutide

MD/RD counseling; web/remote program; structured multidisciplinary program

Medical Therapy:

Lifestyle Modification:

STEP 2

LOW

Stage Severity of Complications

BMI 2526.9,
or BMI 27

B IOMECHANIC AL COMP LIC AT IONS

B M I 2 7 WI TH COM P LI C ATI ONS

C A R DIOM E TA BOL I C D ISEASE

E VA L U AT I O N F O R C O M P L I C AT I O N S A N D S TA G I N G

NO COM PLIC ATIONS

STEP 1

Complications-Centric Model for Care

of the Overweight/Obese Patient

440 AACE/ACE Comprehensive Diabetes Management Algorithm, Endocr Pract. 2015;21(No. 4)

DYSL IPIDE MIA

ROUTE

OV E R T
D I A B E TE S

Progression

Intensify
Weight
Loss
Therapies

1 PRE-DM
C RI TE RI ON

TZD
GLP-1 RA

Metformin
Acarbose

If glycemia not normalized,

consider with caution

Consider with
Caution
Low-risk
Medications

MU LTIPL E PR E- DM
CR ITER IA

FPG > 100 | 2-hour PG > 140

ANTIHYPE R GLYCE MIC T H E R AP IE S

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HYPER T ENSION
ROUTE

N ORMA L
G LYC E M I A

PR OCE E D TO
HYPE R G LYCE MI A
ALG OR I T HM

W EI GHT LOSS
TH ER APIES

C V D R ISK FAC TOR

MO DIFIC ATIONS ALG ORI THM

OT HE R C VD
R ISK FAC TOR S

(Including Medically Assisted Weight Loss)

L I F E S T Y L E M O D I F I C AT I O N

IFG (1 00 1 2 5) | IG T ( 140199) | ME TABOLIC SYN D R OM E (NCE P 2005)

PR EDIABETES ALGOR ITHM

AACE/ACE Comprehensive Diabetes Management Algorithm, Endocr Pract. 2015;21(No. 4) 441

For patients with

concurrent serious
illness and at risk
for hypoglycemia

For patients without

concurrent serious
illness and at low
hypoglycemic risk

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A1c > 6.5%

A1c 6.5%

IN DIVIDUA LIZ E G OA LS

G OALS FOR G LYCE MIC CONT R OL

442 AACE/ACE Comprehensive Diabetes Management Algorithm, Endocr Pract. 2015;21(No. 4)

Triple Therapy

proceed to

in 3 months

If not at goal

or other
1st-line
agent

MET

SU/GLN

AGi

Bromocriptine QR

Colesevelam

Basal Insulin

TZD

DPP-4i

SGLT-2i

GLP-1 RA

D UA L TH ER APY*

Entry A1c 7.5%

Other
Agents

INSULIN

YES

Use with caution

Few adverse events

or possible benefits

Refer to Insulin Algorithm

A DD O R I NTENS I FY
I NS UL I N

TRIPLE
Therapy

OR

DUAL
Therapy

NO

S YMPTO MS

Entry A1c > 9.0%

LEGEND

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O F

insulin therapy

to or intensify

D I S E A S E

SU/GLN

AGi

Bromocriptine QR

Colesevelam

DPP-4i

Basal insulin

TZD

3 months proceed

If not at goal in

or other
1st-line
agent +
2nd-line
agent

SGLT-2i

GLP-1 RA

T R I PL E TH ER APY*

MET

P R O G R E S S I O N

* Order of medications listed represents a suggested hierarchy of usage

proceed to Double Therapy

If not at goal in 3 months

SU/GLN

TZD

AGi

DPP-4i

SGLT-2i

GLP-1 RA

Metformin

M O NO TH E R A PY *

Entry A1c < 7.5%

(Including Medically Assisted Weight Loss)

L I F E S T Y L E M O D I F I C AT I O N

Glyc emic Con t r ol A lg or it hm

AACE/ACE Comprehensive Diabetes Management Algorithm, Endocr Pract. 2015;21(No. 4) 443

TDD 0.20.3 U/kg

TDD 0.10.2 U/kg

Fixed regimen: Increase TDD by 2 U

Adjustable regimen:
FBG > 180 mg/dL: add 20% of TDD
FBG 140180 mg/dL: add 10% of TDD
FBG 110139 mg/dL: add 1 Unit
If hypoglycemia, reduce TDD by:
BG < 70 mg/dL: 10% 20%
BG < 40 mg/dL: 20% 40%

Glycemic
Control Not
at Goal**

0.30.5 U/kg
50% Basal Analog
50% Prandial Analog
Less desirable: NPH
and regular insulin
or premixed insulin

TDD

Add Prandial Insulin

Increase prandial dose by 10% for any meal if the 2-hr

postprandial or next premeal glucose is > 180 mg/dL
Premixed: Increase TDD by 10% if fasting/premeal BG > 180 mg/dL
If fasting AM hypoglycemia, reduce basal insulin
If nighttime hypoglycemia, reduce basal and/or pre-supper or
pre-evening snack short/rapid-acting insulin
If between-meal daytime hypoglycemia, reduce previous
premeal short/rapid-acting insulin

Insulin titration every 23 days to reach glycemic goal:

or DPP-4i

or SGLT-2i

Add GLP-1 RA

I N T E N S I F Y (prandial control)

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<7% for most patients with T2DM; fasting and premeal

BG < 110 mg/dL; absence of hypoglycemia
A1c and FBG targets may be adjusted based on patients
age, duration of diabetes, presence of comorbidities,
diabetic complications, and hypoglycemia risk

**Glycemic Goal:

Consider discontinuing or reducing sulfonylurea after

basal insulin started (basal analogs preferred to NPH)

Insulin titration every 23 days

to reach glycemic goal:

A1c > 8%

A1c < 8%

S T A R T B A S A L (long-acting insulin)

ALGORITHM FOR ADDING/INTENSIF Y ING INSULIN

444 AACE/ACE Comprehensive Diabetes Management Algorithm, Endocr Pract. 2015;21(No. 4)

DM but no other major risk

and/or age <40

<90
<1200

Apo B (mg/dL)

LDL-P (nmol/L)

<1000

<80

<3.0

<150

-blocker

Calcium
Channel
Blocker

Thiazide

If not at goal (23 months)

ACEi
or
ARB

D UAL THER APY

For initial blood pressure

>150/100 mm Hg:

Achievement of target blood

pressure is critical

Additional choices (-blockers,

central agents, vasodilators,
spironolactone)

If not at goal (23 months)

Add next agent from the above

group, repeat

If not at goal (23 months)

Add -blocker or calcium channel

blocker or thiazide diuretic

ACEi
or
ARB

g oAL : systoL iC ~130,

diAstoL iC ~80 mm h g

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* E VE N MORE INT E NSI V E T HER APY MI GHT BE WAR R ANT ED

Assess adequacy & tolerance of therapy with focused laboratory evaluations and patient follow-up

Intensify statin, add ezetimibe &/or colesevelam &/or niacin

Intensify statin &/or add OM3EE &/or fibrates &/or niacin
Intensify statin &/or ezetimibe &/or colesevelam &/or niacin

<3.5

TC/HDL-C

to LowEr LdL-C:
to LowEr non-hdL-C, tg:
to LowEr Apo b, LdL-p:

<150

TG (mg/dL)

<70
<100

Intensify TLC (weight loss, physical activity, dietary changes)

and glycemic control; Consider additional therapy

<130

dEsirAbLE LEVELs

DM + major CVD risk(s) (HTN, Fam Hx,

low HDL-C, smoking) or CVD*

Intensify therapies to
attain goals according
to risk levels

if not At dEsirAbLE LEVELs:

<100

Non-HDL-C (mg/dL)

high

hypErtEnsion
(See Obesity Algorithm)

If TG > 500 mg/dL, fibrates, omega-3

ethyl esters, niacin

Repeat lipid panel;

assess adequacy,
tolerance of therapy

dEsirAbLE LEVELs

ModErAtE

LDL-C (mg/dL)

risK LE VELs

Try alternate statin, lower statin

dose or frequency, or add nonstatin
LDL-C- lowering therapies

If statin-intolerant

stAtin thE r Apy

L ipid pA n E L: Assess CVd risk

thErApEutiC LifEstyLE ChAngEs

dysLipidEMiA

CVD R ISK FACTOR MODIFICATIONS ALGORITH M

AACE/ACE Comprehensive Diabetes Management Algorithm, Endocr Pract. 2015;21(No. 4) 445

Loss

Exenatide
Contraindicated
CrCl < 30

slight
Loss

Contraindicated
CKD
stage
3B,4,5

Moderate

Neutral

Benefit

Neutral

WEIGHT

RENAL/
GU

GI sx

CHF

CVD

BONE
Neutral

Increased
LDL

Neutral

Neutral

Genital
Mycotic
Infections

Loss

Neutral

sGLT-2i

Neutral

Neutral

GLN

Neutral

Moderate
Bone
Loss

Use with caution

Neutral

Neutral

More
Hypo
Risk

Gain

Mild

Moderate/
severe

sU

Neutral

Moderate

Neutral

May
Worsen
Fluid
Retention

Gain

Neutral

TZD

Neutral

safe

Neutral

Moderate

Neutral

Neutral

Neutral

BCR-QR

Neutral

Neutral

Neutral

More
Hypo Risk
& Fluid
Retention

Gain

Moderate
to severe

INsULIN

Likelihood of adverse effects

Neutral

Neutral

Mild

Neutral

Neutral

Neutral

COLsVL

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Neutral

Neutral

Moderate

Neutral

Dose
Adjustment
May be
Necessary
(Except
Linagliptin))

Neutral

Neutral

Neutral

AGi

Neutral

Neutral

DPP-4i

Few adverse events or possible benefits

Neutral

Neutral

Moderate

Neutral

Neutral

GLP-1 RA

HYPO

MET

Pr of ile s of AntidiA betic MedicAt ions

Neutral

Neutral

Moderate

Neutral

Loss

Neutral

PRAML

446 AACE/ACE Comprehensive Diabetes Management Algorithm, Endocr Pract. 2015;21(No. 4)

6)

5)

4)

3)

2)

1)

12)

11)

10)

9)

8)

7)

cations that affect their choice include: risk of

inducing hypoglycemia, risk of weight gain,
ease of use, cost, and safety impact of kidney,
heart, or liver disease. This algorithm includes
every FDA-approved class of medications for
diabetes. This algorithm also stratifies choice
of therapies based on initial A1c.
The algorithm provides guidance to what therapies to initiate and add, but respects individual
circumstances that would make different choices.
Therapies with complementary mechanisms of
action must typically be used in combinations
for optimum glycemic control.
Effectiveness of therapy must be evaluated frequently until stable (e.g. every 3 months) using
multiple criteria including A1c, sMBG records
including both fasting and post-prandial data,
documented and suspected hypoglycemia, and
monitoring for other potential adverse events
(weight gain, fluid retention, hepatic, renal, or
cardiac disease), and monitoring of comorbidities, relevant laboratory data, concomitant drug
administration, diabetic complications, and psycho-social factors affecting patient care.
safety and efficacy should be given higher priorities than initial acquisition cost of medications
per se since cost of medications is only a small
part of the total cost of care of diabetes. In determining the cost of a medication, consideration
should be given to monitoring requirements,
risk of hypoglycemia and weight gain, etc.
The algorithm should be as simple as possible to
gain physician acceptance and improve its utility
and usability in clinical practice.
The algorithm should serve to help educate

This document represents the official position of the

American Association of Clinical Endocrinologists and
the American College of Endocrinology. Where there
were no RCTs or specific FDA labeling for issues in clinical practice, the participating clinical experts utilized
their judgment and experience. Every effort was made
to achieve consensus among the committee members. Many details that could not be included in the
graphic summary (Figure) are described in the text.

All necessary author disclosures are made to AACE and are on

file at the main office. Please contact Lori Clawges at AACE for
further inquiries.

16)

15)

14)

13)

the clinician as well as to guide therapy at the

point of care.
The algorithm should conform, as nearly as possible, to a consensus for current standard of
practice of care by expert endocrinologists who
specialize in the management of patients with
type 2 diabetes and have the broadest experience in outpatient clinical practice.
The algorithm should be as specific as possible,
and provide guidance to the physician with
prioritization and a rationale for selection of
any particular regimen.
Rapid-acting insulin analogs are superior to Regular because they are more predictable.
Long-acting insulin analogs are superior to NPH
insulin because they provide a fairly flat response for approximately 24 hours and provide
better reproducibility and consistency both between subjects and within subjects, with a corresponding reduction in the risk of hypoglycemia.

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Lifestyle optimization and education are essential

for all patients with diabetes. Lifestyle modification designed for weight loss, including medical
and surgical interventions approved for the treatment of obesity, should be considered as primary
approaches for therapeutic benefits in overweight and obese patients with diabetes, and for
prevention of diabetes in high risk patients with
prediabetes. The treatment of overweight/obesity in patients with type 2 diabetes and prediabetes should proceed according to the Obesity
Treatment Algorithm. Effective interventions for
weight loss involve a multidisciplinary team. The
need for medical therapy for weight loss or glycemic control should not be considered as a failure
of lifestyle management, but as an adjunct to it.
The A1c target must be individualized, based on
numerous factors, such as age, comorbid conditions, duration of diabetes, risk of hypoglycemia,
patient motivation, adherence, life expectancy,
etc. An A1c of 6.5% or less is still considered optimal if it can be achieved in a safe and affordable
manner, but higher targets may be appropriate
and may change in a given individual over time.
Minimizing risk of hypoglycemia is a priority. It is
a matter of safety, adherence, and cost.
Minimizing risk of weight gain is a priority. It too
is a matter of safety, adherence, and cost.
Glycemic control targets include fasting and
postprandial glucose as determined by self
blood glucose monitoring.
The choice of therapies must be individualized
based on attributes of the patient (as above)
and the medications themselves (see Profiles of
Antidiabetic Medications). Attributes of medi-

Pr inciPles of the AAce Algorith M

for the tr eAtMent of t yPe 2 diA be te s
AACE/ACE Comprehensive Diabetes Management Algorithm, Endocr Pract. 2015;21(No. 4) 447