ENDOCRINE PRACTICE Rapid Electronic Article in Press

Rapid Electronic Articles in Press are preprinted manuscripts that have been accepted for publication in an issue of

Endocrine Practice

AACE/ACE COMPREHENSIVE
DIABETES MANAGEMENT
ALGORITHM
2015
TA S K F OR CE
Alan J. Garber, MD, PhD, FACE, Chair

Martin J. Abrahamson, MD George Grunberger, MD, FACP, FACE

Joshua I. Barzilay, MD, FACE
Lawrence Blonde, MD, FACP, FACE
Zachary T. Bloomgarden, MD, MACE
Michael A. Bush, MD
Samuel Dagogo-Jack, MD, DM, FRCP, FACE
Michael B. Davidson, DO, FACE
Daniel Einhorn, MD, FACP, FACE
Jeffrey R. Garber, MD, FACP, FACE
W. Timothy Garvey, MD, FACE
Yehuda Handelsman, MD, FACP, FNLA, FACE
Irl B. Hirsch, MD
Paul S. Jellinger, MD, MACE
Janet B. McGill, MD, FACE
Jeffrey I. Mechanick, MD, FACP, FACE, FACN, ECNU
Paul D. Rosenblit, MD, PhD, FNLA, FACE
Guillermo Umpierrez, MD, FACP, FACE
Michael H. Davidson, MD, Advisor

COPYRIGHT © 2015 AACE MAY NOT BE REPRODUCED IN ANY FORM WITHOUT EXPRESS WRITTEN PERMISSION FROM AACE.

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.
 TABLE OF CONTENTS

Com pr e he n si v e Di abe 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

COPYRIGHT © 2015 AACE MAY NOT BE REPRODUCED IN ANY FORM WITHOUT EXPRESS WRITTEN PERMISSION FROM AACE.
 Complications-Centric Model for Care
of the Overweight/Obese Patient

STEP 1 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

C A RD IOM E TA B OL IC D ISEASE B IOMECHANIC AL COMP LIC AT IONS

NO CO MPL IC ATIONS B M I ≥ 2 7 WI TH COM P LI C ATI ON S

BMI 25–26.9, Stage Severity of Complications

or BMI ≥ 27
LOW MEDIUM HIGH

Therapeutic targets for Treatment Treatment intensity for weight

STEP 2 SELEC T: improvement in complications + modality + loss based on staging

Lifestyle Modification: MD/RD counseling; web/remote program; structured multidisciplinary program

phentermine; orlistat; lorcaserin; phentermine/topiramate ER;

Medical Therapy:
naltrexone/bupropion; liraglutide

Surgical Therapy (BMI ≥ 35): Lap band; gastric sleeve; gastric bypass

If therapeutic targets for improvements in complications not met, intensify lifestyle and/or medical
STEP 3 and/or surgical treatment modalities for greater weight loss

COPYRIGHT © 2015 AACE MAY NOT BE REPRODUCED IN ANY FORM WITHOUT EXPRESS WRITTEN PERMISSION FROM AACE.
 PR EDIABETES ALGORITH M
IFG (1 00– 1 2 5) | IG T ( 140–199) | ME TAB OLIC SYN D R OM E (NCE P 2005 )

L I F E S T Y L E M O D I F I C AT I O N
(Including Medically Assisted Weight Loss)

OT HE R C V D W EI GHT LOSS ANTIHYPE R GLYCE MIC T H E R AP IE S

R ISK FAC TORS T HER APIES FPG > 100 | 2-hour PG > 140

C V D R ISK FAC TOR N ORMA L 1 PRE-DM MU LTIPL E PR E- DM

M OD IF IC ATI ON S ALGOR ITH M G LYC E M I A C RI TE RI ON CR ITER IA

DYSL IPIDE MIA HYPE R TE NSION Low-risk Consider with

ROUTE ROUTE Medications Caution
Progression Intensify
Weight Metformin TZD
Loss
Therapies Acarbose GLP-1 RA
OV E R T
D I A B E TE S

PR OCE E D TO
HYPER G LYCEMI A If glycemia not normalized,
ALG OR I T HM consider with caution

COPYRIGHT © 2015 AACE MAY NOT BE REPRODUCED IN ANY FORM WITHOUT EXPRESS WRITTEN PERMISSION FROM AACE.
 G OALS FOR G LYCE MIC CONT R OL

IN DIVIDUA LIZ E G OA LS

A1c ≤ 6.5% A1c > 6.5%

For patients without For patients with
concurrent serious concurrent serious
illness and at low illness and at risk
hypoglycemic risk for hypoglycemia

COPYRIGHT © 2015 AACE MAY NOT BE REPRODUCED IN ANY FORM WITHOUT EXPRESS WRITTEN PERMISSION FROM AACE.
 Glyc em ic Con t r ol A lg or it hm

L I F E S T Y L E M O D I F I C AT I O N
(Including Medically Assisted Weight Loss)

Entry A1c < 7.5% Entry A1c ≥ 7.5% Entry A1c > 9.0%

M O NO T H E R A PY* S YMPTO MS
Metformin D UA L TH ER APY*
NO YES
GLP-1 RA T R I PL E TH ER APY*
GLP-1 RA
SGLT-2i GLP-1 RA DUAL INSULIN
SGLT-2i
Therapy ±
DPP-4i SGLT-2i
DPP-4i Other
MET TZD MET OR Agents
AGi TZD
or other or other
1st-line Basal Insulin 1st-line TRIPLE
TZD Basal insulin
agent agent + Therapy
Colesevelam 2nd-line DPP-4i
SU/GLN
agent
+ Bromocriptine QR Colesevelam
AGi Bromocriptine QR
SU/GLN
+ AGi A DD O R I NTENS I FY
If not at goal in 3 months
SU/GLN
I NS UL I N
If not at goal
proceed to Double Therapy Refer to Insulin Algorithm
in 3 months
proceed to If not at goal in
Triple Therapy 3 months proceed Few adverse events
to or intensify LEGEND or possible benefits
insulin therapy Use with caution
* Order of medications listed represents a suggested hierarchy of usage

P R O G R E S S I O N O F D I S E A S E
COPYRIGHT © 2015 AACE MAY NOT BE REPRODUCED IN ANY FORM WITHOUT EXPRESS WRITTEN PERMISSION FROM AACE.
 ALGORITHM FOR ADDING/INTENSIF Y ING INSULIN

S T A R T B A S A L (long-acting insulin) I N T E N S I F Y (prandial control)

A1c < 8% A1c > 8% Add GLP-1 RA Add Prandial Insulin

or SGLT-2i
or DPP-4i
TDD 0.1–0.2 U/kg TDD 0.2–0.3 U/kg TDD 0.3–0.5 U/kg
t

#BTBM
"OBMPH
Glycemic t

1SBOEJBM
"OBMPH
Insulin titration every 2–3 days
Control Not t
-FTT
EFTJSBCMF
/1)
to reach glycemic goal:
at Goal**
BOE
SFHVMBS
JOTVMJO
t
'JYFE
SFHJNFO
*ODSFBTF
5%%
CZ

6
PS
QSFNJYFE
JOTVMJO
t
"EKVTUBCMF
SFHJNFO
t
FBG 

NHE-
BEE

PG
5%%
t
FBG o
NHE-
BEE

PG
5%%
t
FBG o
NHE-
BEE

6OJU
t
*G
IZQPHMZDFNJB
SFEVDF
5%%
CZ
t
#(


NHE-

o

t
#(


NHE-

o


Consider discontinuing or reducing sulfonylurea after Insulin titration every 2–3 days to reach glycemic goal:
basal insulin started (basal analogs preferred to NPH)
t
*ODSFBTF
QSBOEJBM
EPTF
CZ

GPS
BOZ
NFBM
JG
UIF
IS

QPTUQSBOEJBM
PS
OFYU
QSFNFBM
HMVDPTF
JT


NHE-
**Glycemic Goal: t
1SFNJYFE
*ODSFBTF
5%%
CZ

JG
GBTUJOHQSFNFBM
#(


NHE-
t
*G
GBTUJOH
".
IZQPHMZDFNJB
SFEVDF
CBTBM
JOTVMJO
t

GPS
NPTU
QBUJFOUT
XJUI
5%.
GBTUJOH
BOE
QSFNFBM t
*G
OJHIUUJNF
IZQPHMZDFNJB
SFEVDF
CBTBM
BOEPS
QSFTVQQFS
PS

#(


NHE-
BCTFODF
PG
IZQPHMZDFNJB
QSFFWFOJOH
TOBDL
TIPSUSBQJEBDUJOH
JOTVMJO
t
"D
BOE
'#(
UBSHFUT
NBZ
CF
BEKVTUFE
CBTFE
PO
QBUJFOUT t
*G
CFUXFFONFBM
EBZUJNF
IZQPHMZDFNJB
SFEVDF
QSFWJPVT

BHF
EVSBUJPO
PG
EJBCFUFT
QSFTFODF
PG
DPNPSCJEJUJFT
QSFNFBM
TIPSUSBQJEBDUJOH
JOTVMJO

EJBCFUJD
DPNQMJDBUJPOT
BOE
IZQPHMZDFNJB
SJTL

COPYRIGHT © 2015 AACE MAY NOT BE REPRODUCED IN ANY FORM WITHOUT EXPRESS WRITTEN PERMISSION FROM AACE.
 CVD R ISK FA CTOR M ODIFICATIONS ALGORITHM

DYSLIPIDEMIA HYPERTENSION

THERAPEUTIC LIFESTYLE CHANGES (See Obesity Algorithm)

L IPID PA N EL: Assess CVD Risk G OAL : SYSTOL IC ~130,

DIASTOL IC ~80 mm Hg

If TG > 500 mg/dL, fibrates, omega-3 ACEi For initial blood pressure
STATIN TH E R A PY ethyl esters, niacin or >150/100 mm Hg:
If statin-intolerant ARB D UAL THER APY

Try alternate statin, lower statin Repeat lipid panel; Intensify therapies to Thiazide
dose or frequency, or add nonstatin assess adequacy, attain goals according ACEi Calcium
LDL-C- lowering therapies tolerance of therapy to risk levels
or Channel
Blocker
DM but no other major risk DM + major CVD risk(s) (HTN, Fam Hx,
ARB
RISK LE VELS MODERATE and/or age <40 HIGH low HDL-C, smoking) or CVD* ß-blocker
DESIRABLE LEVELS DESIRABLE LEVELS
LDL-C (mg/dL) <100 <70
If not at goal (2–3 months)
Non-HDL-C (mg/dL) <130 <100
TG (mg/dL) <150 <150 Add ß-blocker or calcium channel
TC/HDL-C <3.5 <3.0 blocker or thiazide diuretic
Apo B (mg/dL) <90 <80
LDL-P (nmol/L) <1200 <1000 If not at goal (2–3 months)

Add next agent from the above

Intensify TLC (weight loss, physical activity, dietary changes)
IF NOT AT DESIRABLE LEVELS: group, repeat
and glycemic control; Consider additional therapy
If not at goal (2–3 months)

TO LOWER LDL-C: Intensify statin, add ezetimibe &/or colesevelam &/or niacin Additional choices (α-blockers,
TO LOWER Non-HDL-C, TG: Intensify statin &/or add OM3EE &/or fibrates &/or niacin central agents, vasodilators,
TO LOWER Apo B, LDL-P: Intensify statin &/or ezetimibe &/or colesevelam &/or niacin spironolactone)

Assess adequacy & tolerance of therapy with focused laboratory evaluations and patient follow-up Achievement of target blood
pressure is critical
* E V EN MORE IN TEN SI V E T HER APY MI GHT BE WAR R ANT ED

COPYRIGHT © 2015 AACE MAY NOT BE REPRODUCED IN ANY FORM WITHOUT EXPRESS WRITTEN PERMISSION FROM AACE.
 PR OFI LES OF ANTIDIA BETIC M EDICAT IONS

MET GLP-1 RA SGLT-2i DPP-4i AGi TZD SU COLSVL BCR-QR INSULIN PRAML
GLN
Moderate/
Severe Moderate
HYPO Neutral Neutral Neutral Neutral Neutral Neutral Neutral Neutral Neutral
Mild to Severe

Slight
WEIGHT Loss Loss Neutral Neutral Gain Gain Neutral Neutral Gain Loss
Loss

Dose
Contra-
Exenatide Adjustment May More
indicated Genital More
RENAL/ Contra- May be Worsen Hypo Risk
CKD Mycotic Neutral Hypo Neutral Neutral Neutral
GU indicated Necessary Fluid & Fluid
Stage Infections Risk
CrCl < 30 (Except Retention Retention
3B,4,5
Linagliptin))

GI Sx Moderate Moderate Neutral Neutral Moderate Neutral Neutral Mild Moderate Neutral Moderate

CHF Neutral Neutral Moderate Neutral Neutral

Neutral Neutral Neutral Neutral Neutral Neutral
Increased
CVD Benefit Neutral ? Safe
LDL

Moderate
BONE Neutral Neutral Neutral Neutral Neutral Bone Neutral Neutral Neutral Neutral Neutral
Loss

Few adverse events or possible benefits Use with caution Likelihood of adverse effects

COPYRIGHT © 2015 AACE MAY NOT BE REPRODUCED IN ANY FORM WITHOUT EXPRESS WRITTEN PERMISSION FROM AACE.
 PR INCIPLES OF THE AACE ALGORITHM
F OR THE TR EATMENT OF T YPE 2 DIA BE TE S
1) Lifestyle optimization and education are essential
for all patients with diabetes. Lifestyle modifica-
tion designed for weight loss, including medical
and surgical interventions approved for the treat-
ment of obesity, should be considered as primary
approaches for therapeutic benefits in over-
weight and obese patients with diabetes, and for
prevention of diabetes in high risk patients with
prediabetes. The treatment of overweight/obe-
sity in patients with type 2 diabetes and predia-
betes 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 glyce-
mic control should not be considered as a failure
of lifestyle management, but as an adjunct to it.
2) The A1c target must be individualized, based on
numerous factors, such as age, comorbid condi-
tions, duration of diabetes, risk of hypoglycemia,
patient motivation, adherence, life expectancy,
etc. An A1c of 6.5% or less is still considered opti-
mal 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.
3) Minimizing risk of hypoglycemia is a priority. It is
a matter of safety, adherence, and cost.
4) Minimizing risk of weight gain is a priority. It too
is a matter of safety, adherence, and cost.
5) Glycemic control targets include fasting and
postprandial glucose as determined by self
blood glucose monitoring.
6) 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-
COPYRIGHT © 2015 AACE MAY NOT BE REPRODUCED IN ANY FORM WITHOUT EXPRESS WRITTEN PERMISSION FROM AACE.
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.
7) The algorithm provides guidance to what thera-
pies to initiate and add, but respects individual
circumstances that would make different choices.
8) Therapies with complementary mechanisms of
action must typically be used in combinations
for optimum glycemic control.
9) Effectiveness of therapy must be evaluated fre-
quently 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 comorbidi-
ties, relevant laboratory data, concomitant drug
administration, diabetic complications, and psy-
cho-social factors affecting patient care.
10) Safety and efficacy should be given higher prior-
ities 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 deter-
mining the cost of a medication, consideration
should be given to monitoring requirements,
risk of hypoglycemia and weight gain, etc.
11) The algorithm should be as simple as possible to
gain physician acceptance and improve its utility
and usability in clinical practice.
12) The algorithm should serve to help educate
the clinician as well as to guide therapy at the
point of care.
13) The algorithm should conform, as nearly as pos-
sible, 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 experi-
ence in outpatient clinical practice.
14) 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.
15) Rapid-acting insulin analogs are superior to Reg-
ular because they are more predictable.
16) Long-acting insulin analogs are superior to NPH
insulin because they provide a fairly flat re-
sponse for approximately 24 hours and provide
better reproducibility and consistency both be-
tween subjects and within subjects, with a corre-
sponding reduction in the risk of hypoglycemia.
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 clin-
ical practice, the participating clinical experts utilized
their judgment and experience. Every effort was made
to achieve consensus among the committee mem-
bers. 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.