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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. This version of the manuscript will be replaced with the final, paginated version after it has been
published in Volume 21, Issue 4, April 2015 Endocrine Practice. DOI:10.4158/EP15693.CS
© 2015 AACE.

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 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

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.

ENDOCRINE PRACTICE Vol 21 No. 4 April 2015 e1

Prediabetes Algorithm III. Profiles of Antidiabetic Medications VIII. 4) TABLE OF CONTENTS Com pr e he n si v e Di abe t e s A lg orit h m I.21(No. Glycemic Control Algorithm V. CVD Risk Factor Modifications Algorithm VII. 2015. Algorithm for Adding/Intensifying Insulin VI. Complications-Centric Model for Care of the Overweight/Obese Patient II.e2 AACE/ACE Comprehensive Diabetes Management Algorithm. Goals of Glycemic Control IV. Principles for Treatment of Type 2 Diabetes COPYRIGHT © 2015 AACE MAY NOT BE REPRODUCED IN ANY FORM WITHOUT EXPRESS WRITTEN PERMISSION FROM AACE. . Endocr Pract.

Medical Therapy: naltrexone/bupropion. phentermine/topiramate ER. Stage Severity of Complications or BMI ≥ 27 LOW MEDIUM HIGH S TEP 2 SELEC T: Therapeutic targets for improvement in complications + Treatment modality + Treatment intensity for weight loss based on staging Lifestyle Modification: MD/RD counseling. Endocr Pract. 2015. 4) e3 S TEP 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 ARDI O ME TAB OLIC D ISEASE B IOMECHANIC A L COM P L IC AT IONS NO COM PLIC AT IONS B M I ≥ 2 7 WI TH COM P LI C ATION S BMI 25–26. gastric sleeve. orlistat. gastric bypass If therapeutic targets for improvements in complications not met. liraglutide Surgical Therapy (BMI ≥ 35): Lap band. structured multidisciplinary program phentermine.21(No. intensify lifestyle and/or medical S TEP 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. lorcaserin.9. web/remote program. Complications-Centric Model for Care of the Overweight/Obese Patient AACE/ACE Comprehensive Diabetes Management Algorithm. .

21(No. Endocr Pract. . e4 AACE/ACE Comprehensive Diabetes Management Algorithm. 4) PREDIABETES ALGORITH M I F G ( 1 0 0 – 125) | 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) OTHER C VD WE IG HT LOSS ANTIHYPE R GLYCE M IC T H E R A P IE S RISK FAC TO RS T HER APIES FPG > 100 | 2-hour PG > 140 C VD RISK FAC TOR N ORMA L 1 PRE-DM MU LTIPL E PR E-DM MODIFIC AT IONS ALGORIT HM G LYC E M I A C RI TE RI ON CR ITER IA DYS L IPIDE M IA HYPE R T E 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. 2015.

Endocr Pract.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. G OA LS FOR G LYCE MIC CONT R OL INDIVIDUA LIZ E G OA LS AACE/ACE Comprehensive Diabetes Management Algorithm. .21(No. 2015.5% A1c > 6. 4) e5 A1c ≤ 6.

2015.5% Entry A1c ≥ 7. 4) G lyc e m ic Con t r ol A lg or ithm 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 < 7.0% MON O T H E R A PY* S YM PTO M S D UAL TH ER APY* Metformin NO YE S GLP-1 RA T R I PL E TH ER APY* GLP-1 RA SGLT-2i GLP-1 RA DUAL INSULIN SGLT-2i DPP-4i Therapy ± DPP-4i SGLT-2i Other AGi MET TZD MET TZD OR Agents or other or other 1st-line Basal Insulin 1st-line TRIPLE TZD Basal insulin Therapy + agent agent + Colesevelam DPP-4i SU/GLN 2nd-line + 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.5% Entry A1c > 9. . e6 AACE/ACE Comprehensive Diabetes Management Algorithm. Endocr Pract.21(No.

2–0.1–0.3–0.IZQPHMZDFNJB SFEVDFCBTBMJOTVMJO t GPSNPTUQBUJFOUTXJUI5%. 4) e7 A1c < 8% A1c > 8% Add GLP-1 RA Add Prandial Insulin or SGLT-2i or DPP-4i TDD 0. .GBTUJOHBOEQSFNFBM t *GOJHIUUJNFIZQPHMZDFNJB SFEVDFCBTBMBOEPSQSFTVQQFSPS  #(NHE-BCTFODFPGIZQPHMZDFNJB  QSFFWFOJOHTOBDLTIPSUSBQJEBDUJOHJOTVMJO t "DBOE'#(UBSHFUTNBZCFBEKVTUFECBTFEPOQBUJFOUT t *GCFUXFFONFBMEBZUJNFIZQPHMZDFNJB SFEVDFQSFWJPVT  BHF EVSBUJPOPGEJBCFUFT QSFTFODFPGDPNPSCJEJUJFT  QSFNFBMTIPSUSBQJEBDUJOHJOTVMJO  EJBCFUJDDPNQMJDBUJPOT BOEIZQPHMZDFNJBSJTL COPYRIGHT © 2015 AACE MAY NOT BE REPRODUCED IN ANY FORM WITHOUT EXPRESS WRITTEN PERMISSION FROM AACE. Endocr Pract.2 U/kg TDD 0. 2015.3 U/kg TDD 0.5 U/kg t #BTBM"OBMPH Glycemic t 1SBOEJBM"OBMPH Insulin titration every 2–3 days to reach glycemic goal: Control Not t -FTTEFTJSBCMF/1) at Goal**  BOESFHVMBSJOTVMJO t 'JYFESFHJNFO*ODSFBTF5%%CZ6  PSQSFNJYFEJOTVMJO t "EKVTUBCMFSFHJNFO t FBG NHE-BEEPG5%% t FBG oNHE-BEEPG5%% t FBG oNHE-BEE6OJU t *GIZQPHMZDFNJB SFEVDF5%%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 *ODSFBTFQSBOEJBMEPTFCZGPSBOZNFBMJGUIFIS  QPTUQSBOEJBMPSOFYUQSFNFBMHMVDPTFJTNHE- **Glycemic Goal: t 1SFNJYFE*ODSFBTF5%%CZJGGBTUJOHQSFNFBM#(NHE- t *GGBTUJOH". A LG ORITH M FOR ADDING/INTENSIF YING 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) AACE/ACE Comprehensive Diabetes Management Algorithm.21(No.

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. e8 AACE/ACE Comprehensive Diabetes Management Algorithm. Endocr Pract. add ezetimibe &/or colesevelam &/or niacin Additional choices (α-blockers. Intensify therapies to Thiazide dose or frequency. TG: Intensify statin &/or add OM3EE &/or fibrates &/or niacin central agents. vasodilators.lowering therapies tolerance of therapy to risk levels or Channel Blocker DM but no other major risk DM + major CVD risk(s) (HTN. TO LOWER Apo B. 2015. lower statin Repeat lipid panel. or add nonstatin assess adequacy. dietary changes) IF NOT AT DESIRABLE LEVELS: group. Consider additional therapy If not at goal (2–3 months) TO LOWER LDL-C: Intensify statin. . attain goals according ACEi Calcium LDL-C. TO LOWER Non-HDL-C. DIASTOL IC ~80 mm Hg If TG > 500 mg/dL. 4) CVD RISK FACTOR M ODIFICATIONS ALGORITHM DYSLIPIDEMIA HYPERTENSION THERAPEUTIC LIFESTYLE CHANGES (See Obesity Algorithm) LIPID PA N EL: Assess CVD Risk G OAL : SYSTOL IC ~130. fibrates. physical activity. omega-3 ACEi For initial blood pressure STAT IN T HE R APY ethyl esters. Fam Hx.5 <3. 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. 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 E N M O RE I NT ENSI 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. niacin or >150/100 mm Hg: If statin-intolerant ARB D UAL THER APY Try alternate statin. repeat and glycemic control.21(No.

21(No. 4) e9 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. Endocr Pract. May be Worsen Hypo Risk CKD Mycotic Neutral Hypo Neutral Neutral Neutral GU Stage indicated Infections Necessary Fluid Risk & Fluid CrCl < 30 (Except Retention Retention 3B. PR OFI L ES OF ANTIDIA BETIC M EDICAT ION S MET GLP-1 RA SGLT-2i DPP-4i AGi TZD SU COLSVL BCR-QR INSULIN PRAML GLN AACE/ACE Comprehensive Diabetes Management Algorithm.4. . 2015.5 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.

heart. Endocr Pract. should be considered as primary every FDA-approved class of medications for practice of care by expert endocrinologists who approaches for therapeutic benefits in over. Every effort was made is a matter of safety. . cardiac disease). tion designed for weight loss. documented and suspected hypoglycemia. and better reproducibility and consistency both be- tions. adherence. 4) PR INCIPLES OF THE AACE ALGORITHM F OR THE TR EATMENT OF T YPE 2 DIABETES 1) Lifestyle optimization and education are essential cations that affect their choice include: risk of the clinician as well as to guide therapy at the for all patients with diabetes. sity in patients with type 2 diabetes and predia.g. comorbid condi. circumstances that would make different choices. It is 10) Safety and efficacy should be given higher prior- were no RCTs or specific FDA labeling for issues in clin- a matter of safety. ities than initial acquisition cost of medications ical practice. In deter. Lifestyle modifica. type 2 diabetes and have the broadest experi- prevention of diabetes in high risk patients with 7) The algorithm provides guidance to what thera. graphic summary (Figure) are described in the text. (weight gain. file at the main office. such as age. part of the total cost of care of diabetes. risk of hypoglycemia. as nearly as pos- and surgical interventions approved for the treat. Please contact Lori Clawges at AACE for Antidiabetic Medications). fluid retention. renal. monitoring for other potential adverse events tween subjects and within subjects. weight loss involve a multidisciplinary team. inducing hypoglycemia. ence in outpatient clinical practice. or liver disease. the American College of Endocrinology. risk of weight gain. etc. 2015. sponse for approximately 24 hours and provide numerous factors. duration of diabetes. but respects individual 14) The algorithm should be as specific as possible. adherence. hepatic. The for optimum glycemic control. Attributes of medi. prediabetes. Many details that could not be included in the postprandial glucose as determined by self should be given to monitoring requirements. COPYRIGHT © 2015 AACE MAY NOT BE REPRODUCED IN ANY FORM WITHOUT EXPRESS WRITTEN PERMISSION FROM AACE. and safety impact of kidney. life expectancy. SMBG records insulin because they provide a fairly flat re- 2) The A1c target must be individualized. and cost. 15) Rapid-acting insulin analogs are superior to Reg- need for medical therapy for weight loss or glyce. diabetic complications. An A1c of 6. This algorithm also stratifies choice specialize in the management of patients with weight and obese patients with diabetes. adherence. but higher targets may be appropriate administration. mic control should not be considered as a failure quently until stable (e. to a consensus for current standard of ment of obesity. pies to initiate and add. relevant laboratory data. 12) The algorithm should serve to help educate further inquiries. The treatment of overweight/obe.21(No. cost. point of care. and provide guidance to the physician with betes should proceed according to the Obesity 8) Therapies with complementary mechanisms of prioritization and a rationale for selection of Treatment Algorithm. including medical ease of use. blood glucose monitoring. cho-social factors affecting patient care. ular because they are more predictable. and monitoring of comorbidi- mal if it can be achieved in a safe and affordable ties. 13) The algorithm should conform. 9) Effectiveness of therapy must be evaluated fre. and for of therapies based on initial A1c. multiple criteria including A1c. e10 AACE/ACE Comprehensive Diabetes Management Algorithm. risk of hypoglycemia and weight gain. with a corre- patient motivation.5% or less is still considered opti. the participating clinical experts utilized 4) Minimizing risk of weight gain is a priority. and cost. 6) The choice of therapies must be individualized 11) The algorithm should be as simple as possible to based on attributes of the patient (as above) gain physician acceptance and improve its utility All necessary author disclosures are made to AACE and are on and the medications themselves (see Profiles of and usability in clinical practice. Effective interventions for action must typically be used in combinations any particular regimen. and psy. or sponding reduction in the risk of hypoglycemia. to achieve consensus among the committee mem- 5) Glycemic control targets include fasting and mining the cost of a medication. every 3 months) using 16) Long-acting insulin analogs are superior to NPH of lifestyle management. concomitant drug manner. It too per se since cost of medications is only a small their judgment and experience. etc. Where there 3) Minimizing risk of hypoglycemia is a priority. This algorithm includes sible. This document represents the official position of the American Association of Clinical Endocrinologists and and may change in a given individual over time. but as an adjunct to it. diabetes. based on including both fasting and post-prandial data. consideration bers.