AACE 2019 Diabetes Algorithm 03.2021

2 0
AM E RI C A N A S S O CI A TI O N O F CL I NICAL ENDOCRINOLOGY
AA C E CO M P R E H E NS I V E
TY P E 2 DI A BE T E S
MAN AG E M E N T A L G O R I T H M
2 0
COPYRIGHT © 2020 AACE | MAY NOT BE REPRODUCED IN ANY FORM WITHOUT EXPRESS WRITTEN PERMISSION FROM AACE.
WWW.AACE.COM/PUBLICATIONS/JOURNAL-REPRINTS-COPYRIGHTS-PERMISSIONS | DOI 10.4158/CS-2019-0472
Marcelle Coviello
COPYRIGHT © 2020- AACE
marcellecoviello@hotmail.com - IP:FORM
| MAY NOT BE REPRODUCED IN ANY 179.190.120.194
WITHOUT EXPRESS WRITTEN PERMISSION FROM AACE. WWW.AACE.COM/PUBLICATIONS/JOURNAL-REPRINTS-COPYRIGHTS-PERMISSIONS | DOI 10.4158/CS-2019-0472
TABLE OF CONTENTS
COMPREHENSIVE TYPE 2 DIABETES MANAGEMENT ALGORITHM
I. Principles for Treatment of Type 2 Diabetes
II. Lifestyle Therapy
III. Complications-Centric Model for Care of the Patient with Overweight/Obesity
IV. Prediabetes
V. ASCVD Risk Factor Modifications
VI. Glycemic Control
VII. Adding/Intensifying Insulin
VIII. Profiles of Antihyperglycemic Medications
Marcelle Coviello
PRINCIPLES OF THE AACE/ACE COMPREHENSIVE
TYPE 2 DIABETES MANAGEMENT ALGORITHM
1. Lifestyle modification underlies all therapy (e.g., weight control, physical activity, sleep, etc.)
2. Avoid hypoglycemia
3. Avoid weight gain
4. Individualize all glycemic targets (A1C, FPG, PPG)
5. Optimal A1C is ≤6.5%, or as close to normal as is safe and achievable
6. Therapy choices are patient centric based on A1C at presentation and shared decision-making
7. Choice of therapy reflects ASCVD, CHF, and renal status
8. Comorbidities must be managed for comprehensive care
9. Get to goal as soon as possible—adjust at ≤3 months until at goal
10. Choice of therapy includes ease of use and affordability
11. CGM is highly recommended, as available, to assist patients in reaching goals safely
Marcelle Coviello
LIFESTYLE THERAPY
RISK STRATIFICATION FOR DIABETES COMPLICATIONS
INTENSITY STRATIFIED BY BURDEN OF OBESITY AND RELATED COMPLICATIONS

• Maintain optimal weight • Avoid trans fatty
+ +
• Calorie restriction acids; limit • Structured
(manage increased weight) saturated fatty
Nutrition counseling
• Plant-based diet; acids
• Meal replacement
high polyunsaturated and • Technological
monounsaturated fatty acids aids
+ +
• 150 min/week moderate exertion • Structured
• Medical evaluation/
Physical (e.g., walking, stair climbing) program
clearance
Activity • Strength training • Wearable
• Medical supervision
• Increase as tolerated technologies
Sleep
• About 6-8 hours per night
• Basic sleep hygiene + • Screen sleep
disturbances
• Home sleep study + • Referral to sleep study
Behavioral
Support
• Community engagement
• Alcohol moderation + • Discuss mood
with HCP + • Formal behavioral
therapy
Smoking
Cessation
• No tobacco products
+ • Nicotine replacement
therapy and medica-
tions as tolerated + • Referral to
structured program
Marcelle Coviello
COMPLICATIONS-CENTRIC MODEL FOR CARE OF THE PATIENT WITH
OVERWEIGHT/OBESITY (ADIPOSITY-BASED CHRONIC DISEASE)
S T EP 1 EVA LU AT I ON FOR COMPLI CAT I ONS AND STAGING
CARDIOMETABOLIC DISEASE | BIOMECHANICAL COMPLICATIONS
BMI <25 NO COMPLICATIONS COMPLICATIONS
NO OVERWEIGHT BMI ≥25 BMI ≥25

OR OBESITY OVERWEIGHT OR OBESITY MILD TO MODERATE SEVERE
STAGE 0 STAGE 1 STAGE 2
S T EP 2 S E LE CT:
Therapeutic targets for
improvement in complications + Treatment
modality + Treatment intensity based
on staging
Lifestyle Therapy: Physician/RD counseling, web/remote program, structured multidisciplinary program
Medical Individualize care by selecting one of the following based on efficacy, safety,
Therapy and patients’ clinical profile: phentermine, orlistat, lorcaserin,
(BMI ≥27): phentermine/topiramate ER, naltrexone/bupropion, liraglutide 3 mg
Surgical Therapy (BMI ≥35): Endoscopic procedures, gastric banding, sleeve, or bypass
If therapeutic targets for complications not met, intensify lifestyle, medical, and/or surgical treatment
S TE P 3 modalities for greater weight loss. Obesity is a chronic progressive disease and requires commitment to
long-term therapy and follow-up.
Marcelle Coviello
PREDIABETES ALGORITHM
IFG (100–125) | IGT (140–199) | METABOLIC SYNDROME (NCEP 2001)
LIFESTYLE THERAPY
(Including Medically Assisted Weight Loss)
TREAT ASCVD WEI GHT LOS S TREAT HYPERGLYCEMIA

RISK FACTORS THE RAP IES FPG >100 | 2-hour PG >140
ASCVD RISK FACTOR NORMAL 1 PRE-DM MULTIPLE PRE-DM

MODIFICATIONS ALGORITHM GLYCEMIA CRITERION CRITERIA
DYSLIPIDEMIA HYPERTENSION
Low-risk Consider with
ROUTE ROUTE
Progression Intensify Medications Caution
Weight
Loss Metformin TZD
Therapies
OVERT Acarbose GLP-1RA
DIABETES
LEGEND
Orlistat, lorcaserin,
phentermine/topiramate ER, PROCEED TO
naltrexone/bupropion, liraglutide 3 mg, GLYCEMIC CONTROL If hyperglycemia persists
or bariatric surgery as indicated
for obesity treatment
ALGORITHM
Marcelle Coviello
ASCVD RISK FACTOR MODIFICATIONS ALGORITHM
D Y S L I PIDE MIA HYPERTEN SION

L I F E S T Y L E T H E R A P Y (Including Medically Assisted Weight Loss)
LI P I D P ANEL: Assess ASCVD Risk GO A L : SY ST O L I C < 1 3 0 ,

D I A ST O L I C < 8 0 m m H g
STATI N T HER A PY
If TG >500 mg/dL, fibrates, Rx-grade OM-3 fatty acids, niacin ACEi For initial blood pressure
or >150/100 mm Hg:
If statin-intolerant
ARB DUAL THERAPY
Try alternate statin, lower statin Repeat lipid panel; Intensify therapies to
dose or frequency, or add nonstatin assess adequacy, attain goals according Calcium
LDL-C- lowering therapies tolerance of therapy to risk levels
Channel
ACEi
Blocker
RISK LEVELS HIGH VERY HIGH EXTREME RISK LEVELS: or
HIGH*: ARB ß-blocker
DESIRABLE LEVELS DESIRABLE LEVELS DESIRABLE LEVELS DM but no other major
risk and/or age <40
LDL-C (mg/dL) <100 <70 <55 Thiazide
VERY HIGH*:
DM + major ASCVD
Non-HDL-C (mg/dL) <130 <100 <80 risk(s) (HTN, Fam Hx,
low HDL-C, smoking,
CKD3,4) If not at goal (2–3 months)
TG (mg/dL) <150 <150 <150
EXTREME*:
DM plus established Add calcium channel blocker,
ß-blocker or thiazide diuretic
Apo B (mg/dL) <90 <80 <70 clinical CVD
Intensify lifestyle therapy (weight loss, physical activity, dietary If not at goal (2–3 months)
If not at desirable levels:
changes) and glycemic control; consider additional therapy
Add next agent from the above
group, repeat
To lower LDL-C: Intensify statin, add ezetimibe, PCSK9i, colesevelam, or niacin
To lower Non-HDL-C, TG: Intensify statin and/or add Rx-grade OM3 fatty acid, fibrate, and/or niacin If not at goal (2–3 months)
To lower Apo B, LDL-P: Intensify statin and/or add ezetimibe, PCSK9i, colesevelam, and/or niacin
To lower LDL-C in FH:** Statin + PCSK9i Additional choices (α-blockers,
central agents, vasodilators,
aldosterone antagonist)
If TG 135-499: Add icosapent ethyl 4 g/day if high ASCVD risk on maximally tolerated statins
Achievement of target blood
Assess adequacy & tolerance of therapy with focused laboratory evaluations and patient follow-up pressure is critical
* EV E N M O R E I NT E NS IV E TH E R APY MIGH T BE WAR R AN TED * * FA MI L I AL HYPERC HO L EST ERO L EMI A
Marcelle Coviello
GLYCEMIC CONTROL ALGORITHM
INDIVIDUALIZE For patients without concurrent serious For patients with concurrent serious
GOALS A1C ≤6.5% illness and at low hypoglycemic risk A1C >6.5% illness and at risk for hypoglycemia
LIFESTYLE THERAPY AND ONGOING GLUCOSE MONITORING (CGM preferred)
COPYRIGHT © 2020 AACE | MAY NOT BE REPRODUCED IN ANY FORM WITHOUT EXPRESS WRITTEN PERMISSION FROM AACE.
WWW.AACE.COM/PUBLICATIONS/JOURNAL-REPRINTS-COPYRIGHTS-PERMISSIONS | DOI 10.4158/CS-2019-0472
INDEPENDENT OF GLYCEMIC CONTROL, IF ESTABLISHED OR HIGH ASCVD RISK AND/OR CKD, RECOMMEND SGLT2i AND/OR LA GLP1-RA
Entry A1C ≥7.5% - 9.0% Entry A1C >9.0%
TRIPLE THERAPY1 S YMPTOM S

DUAL THERAPY1
GLP1-RA NO Y ES
GLP1-RA
Entry A1C <7.5%
Independent of
SGLT2i DUAL
glycemic SGLT2i INSULIN
MONOTHERAPY1,2 Therapy ±
3 MONTHS2
3 MONTHS2
control, if TZD
Metformin DPP4i Other
established
ASCVD or high SU/GLN
OR Agents
GLP1-RA TZD
risk, CKD 3, or
SGLT2i Basal Insulin TRIPLE
HFrEF, start LA SU/GLN Therapy
DPP4i GLP1-RA or DPP4i
Basal Insulin
TZD SGLT2i with
proven Colesevelam
AGi Colesevelam
efficacy*
SU/GLN Bromocriptine QR
Bromocriptine QR A D D OR INTE NSIF Y
AGi AGi INSU L IN
Refer to Insulin Algorithm
MET
+
LEGEND
or other agent Few adverse events and/or
possible benefits
1 Order of medications represents a suggested hierarchy of usage; length of line reflects strength of recommendation
2 If not at goal in 3 months, proceed to next level therapy Use with caution
*CKD 3: canagliflozin; HFrEF: dapagliflozin
CKD 3 = stage 3 chronic kidney disease; HFrEF = heart failure with reduced ejection fraction; LA = long-acting (≥24 hour duration)
Marcelle Coviello
| MAY NOT BE REPRODUCED IN ANY P REXPRESS
O GWRITTEN
179.190.120.194
WITHOUT R E PERMISSION
S S I O NAACE.OWWW.AACE.COM/PUBLICATIONS/JOURNAL-REPRINTS-COPYRIGHTS-PERMISSIONS
FROM F D I S E A S E | DOI 10.4158/CS-2019-0472
ALGORITHM FOR ADDING/INTENSIFYING INSULIN
S T A R T B A S A L (Long-Acting Insulin) INTE NSIF Y (Prandial Control)
A1C <8% A1C >8% Add Add Prandial Insulin

GLP1-RA
TDD 0.1–0.2 U/kg TDD 0.2–0.3 U/kg Or SGLT2i

Or DPP4i
Basal Plus 1, Basal Bolus

Insulin titration every 2–3 days Plus 2, Plus 3
to reach glycemic goal:
• Begin prandial • Begin prandial
• Fixed regimen: Increase TDD by 2 U insulin before insulin before
• Adjustable regimen: largest meal each meal
Glycemic
• FBG >180 mg/dL: add 20% of TDD • If not at goal, • 50% Basal /
Control Not
• FBG 140–180 mg/dL: add 10% of TDD progress to 50% Prandial
• FBG 110–139 mg/dL: add 1 unit
at Goal* injections before TDD 0.3–0.5 U/kg
• If hypoglycemia, reduce TDD by: 2 or 3 meals
• BG <70 mg/dL: 10% – 20%
• BG <40 mg/dL: 20% – 40% • Start: 10% of • Start: 50% of TDD
basal dose or in three doses
5 units before meals
Consider discontinuing or reducing sulfonylurea after
starting basal insulin (basal analogs preferred to NPH)
Insulin titration every 2–3 days to reach glycemic goal:
*Glycemic Goal:
• Increase prandial dose by 10% or 1-2 units if 2-h postprandial
or next premeal glucose consistently >140 mg/dL
• <7% for most patients with T2D; fasting and premeal
BG <110 mg/dL; absence of hypoglycemia • If hypoglycemia, reduce TDD basal and/or prandial insulin by:
• A1C and FBG targets may be adjusted based on patient’s age, • BG consistently <70 mg/dL: 10% - 20%
duration of diabetes, presence of comorbidities, diabetic • Severe hypoglycemia (requiring assistance from another
complications, and hypoglycemia risk person) or BG <40 mg/dL: 20% - 40%
Marcelle Coviello
PROFILES OF ANTIHYPERGLYCEMIC MEDICATIONS
TZD SU
MET GLP1-RA SGLT2i DPP4i AGi (moderate COLSVL BCR-QR INSULIN PRAML
dose) GLN
Moderate/
Severe Moderate
HYPO Neutral Neutral Neutral Neutral Neutral Neutral Neutral Neutral Neutral
Mild
to Severe
WEIGHT Slight Loss Loss Loss Neutral Neutral Gain Gain Neutral Neutral Gain Loss
Not Indicated for

eGFR <45 mL/
Exenatide min/1.73 m2 Dose
Not Adjustment
Contra- Indicated See #1 Necessary
indicated CrCl <30 (Except
More More
RENAL / GU if eGFR <30 Genital Mycotic Linagliptin) Neutral Neutral Neutral Neutral Neutral
Hypo Risk Hypo Risk
mL/min/ Infections
1.73 m2 Effective in
Potential Reducing
Potential CKD Albuminuria
Benefit of
Benefit; See #1
LA GLP1-RA
GI Sx Moderate Moderate Neutral Neutral Moderate Neutral Neutral Mild Moderate Neutral Moderate
Prevent HF
CHF Neutral Hospitalization Moderate Neutral Neutral Neutral CHF Risk
Manage HFrEF; See #2
CARDIAC Neutral See #4 Neutral Neutral
Potential May Possible
Lowers
ASCVD Benefit of See #3 Reduce ASCVD Safe Neutral
LDL-C
LA GLP1-RA Stroke Risk Risk
Moderate
BONE Neutral Neutral Neutral Neutral Neutral Fracture Neutral Neutral Neutral Neutral Neutral
Risk
DKA Can Occur

KETOACIDOSIS Neutral Neutral in Various Neutral Neutral Neutral Neutral Neutral Neutral Neutral Neutral
Stress Settings
COPYRIGHT © 2020 AACE | MAY NOT BE

Few adverse events or possible benefits 1. Canagliflozin indicated for eGFR ≥30 mL/min/1.73 m2 in patients with CKD 3 + albuminuria. REPRODUCED IN ANY FORM WITHOUT EXPRESS
2. Dapagliflozin—potential primary prevention of HF hospitalization & demonstrated efficacy in HFrEF. WRITTEN PERMISSION FROM AACE.
Use with caution
3. Empagliflozin—FDA approved to reduce CV mortality. Canagliflozin—FDA approved to reduce MACE events. WWW.AACE.COM/PUBLICATIONS/JOURNAL-
Likelihood of adverse effects 4. Possible increased hospitalizations for heart failure with alogliptin and saxagliptin. REPRINTS-COPYRIGHTS-PERMISSIONS
Marcelle Coviello
| MAY NOT BE REPRODUCED IN ANY 179.190.120.194 DOI 10.4158/CS-2019-0472

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2 0

I. Principles for Treatment of Type 2 Diabetes

II. Lifestyle Therapy

III. Complications-Centric Model for Care of the Patient with Overweight/Obesity

V. ASCVD Risk Factor Modifications

VI. Glycemic Control

VII. Adding/Intensifying Insulin

VIII. Profiles of Antihyperglycemic Medications

3. Avoid weight gain

4. Individualize all glycemic targets (A1C, FPG, PPG)

5. Optimal A1C is ≤6.5%, or as close to normal as is safe and achievable

7. Choice of therapy reflects ASCVD, CHF, and renal status

8. Comorbidities must be managed for comprehensive care

9. Get to goal as soon as possible—adjust at ≤3 months until at goal

10. Choice of therapy includes ease of use and affordability

INTENSITY STRATIFIED BY BURDEN OF OBESITY AND RELATED COMPLICATIONS

S T EP 1 EVA LU AT I ON FOR COMPLI CAT I ONS AND STAGING

CARDIOMETABOLIC DISEASE | BIOMECHANICAL COMPLICATIONS

BMI <25 NO COMPLICATIONS COMPLICATIONS

NO OVERWEIGHT BMI ≥25 BMI ≥25

STAGE 0 STAGE 1 STAGE 2

Lifestyle Therapy: Physician/RD counseling, web/remote program, structured multidisciplinary program

TREAT ASCVD WEI GHT LOS S TREAT HYPERGLYCEMIA

ASCVD RISK FACTOR NORMAL 1 PRE-DM MULTIPLE PRE-DM

D Y S L I PIDE MIA HYPERTEN SION

LI P I D P ANEL: Assess ASCVD Risk GO A L : SY ST O L I C < 1 3 0 ,

* EV E N M O R E I NT E NS IV E TH E R APY MIGH T BE WAR R AN TED * * FA MI L I AL HYPERC HO L EST ERO L EMI A

LIFESTYLE THERAPY AND ONGOING GLUCOSE MONITORING (CGM preferred)

Entry A1C ≥7.5% - 9.0% Entry A1C >9.0%

TRIPLE THERAPY1 S YMPTOM S

S T A R T B A S A L (Long-Acting Insulin) INTE NSIF Y (Prandial Control)

A1C <8% A1C >8% Add Add Prandial Insulin

TDD 0.1–0.2 U/kg TDD 0.2–0.3 U/kg Or SGLT2i

Basal Plus 1, Basal Bolus

Not Indicated for

DKA Can Occur

COPYRIGHT © 2020 AACE | MAY NOT BE

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