management of type 2 diabetes: non-insulin and insulin ......move to step 2 or 3 if a1c is not at...

Version: Naing/1-2019

For digital copy, please visit http://www.fresno.ucsf.edu/internal-medicine/endo_downloads/ or email [email protected].

Quick Reference Guide 1/2019 version

Management of Type 2 Diabetes:

Non-insulin and Insulin Therapies

Soe Naing, MD, MRCP(UK), FACE

Associate Clinical Professor of MedicineDirector of Division of Endocrinology

Medical Director of Community Diabetes Care CenterUCSF-Fresno Medical Education Program

http://www.fresno.ucsf.edu/internal-medicine/endo_downloads/

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Moderate hyperglycemiaA1c 8-10% or A1c 1.5% above target

Mild hyperglycemiaA1c <8%

Severe hyperglycemiaA1c >10% or

Random BG ≥300 mg/dl orFasting BG ≥250 mg/dl

Monotherapywith metformin

Dual therapy Metformin + 2nd agent*

asymptomatic

Severe symptomsWeight loss

DKA/Hyperosmolar stateSevere infection/surgery

Triple therapy Metformin + 2nd + 3rd agent*

Insulin therapySee page 4 and 7

If A1c is not at goal in 3 months, move to next step.

† healthy eating, increased physical activity, weight loss, and referral to a diabetes center for self-management education and medical nutrition therapy

* A patient-centered approach should be used to guide the choice of glucose-lowering medication. Considerations include the patient- and drug-specific factors,

efficacy, cost, benefit, risk, patient’s characteristics and patient’s preference. (see page 5)

Management of Type 2 Diabetes : Overview

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3

Intensive Lifestyle Modification†

If A1c is not at goal in 3 months, move to next step.

One injection daily(basal insulin)

Two injections daily(Basal+1 regimen or

Pre-mixed insulin)

Multiple injections daily(Basal Prandial therapy)

Step 1

Step 2

Step 3

Add GLP-1 Receptor Agonist

to basal insulin

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Overview of Insulin Therapy (Basic)See page 7 for insulin initiation and titration guide.

4

5 Major

groupsInsulin Sensitizers Insulin Providers GLP1-based therapy Glucose Absorption

InhibitorOthers (less popular)

12

Classes

Biguanide

(Metformin)

Thiazolidi-

nedione

Insulin secretagogues Insulin DPP4

Inhibitors

GLP-1

Receptor

Agonists

SGLT2 Inhibitors α Glucosi-

dase

Inhibitors

Bile Acid

Sequestrant

Dopamine

Agonist

Amylin

MimeticsSulfonylurea Glinides

COST Low Low Low Moderate Low (NPH/R) High High High Moderate High High High

HYPOGLY-

CEMIA RISKNo No Yes Yes Yes No No No No No No No

WEIGHT Loss (modest) Gain Gain Gain Gain Neutral Loss Loss Neutral Neutral Neutral Loss

ASCVD + or CHF +

(CV Risk &Benefit)

Potential

ASCVD

benefit

Potential

ASCVD

benefit with

pioglitazone.

↑ CHF risk

Uncertain

cardiovas-

cular safety

Uncertain

cardiovas-

cular safety

Neutral ↑ CHF Risk

with

SaxagliptinAlogliptin

CV benefit

with Lira- or

Sema-glutide

CV benefit

with Empa- or

Cana-gliflozin

Neutral Neutral ? ↓ ASCVD

events

Neutral

Preferred add-

on if ASCVD+

Preferred add-on if

CHF+ or ASCVD+

CKD +(see page 15

for details)

Contraindicat-

ed if eGFR <30

Do not start or

to reduce

current dose if

eGFR <45.

No dose

adjustment

needed

Avoid

Glyburide

(See page 15)

Repaglinide

can be used

in advanced

CKD/ESRD.

Lower doses

required if

eGFR ↓

Linagliptin –

no need to

adjust dose.

Others – to

reduce dose.

Exenatide –

avoid if eGFR

<30.

Others – no

need to adjust.

Empa- and Cana-

- avoid if eGFR <45

Dapa- and Ertu-

gliflozin

-avoid if eGFR <60

Avoid if

eGFR <30

No dose

adjustment

needed

No dose

adjustment

needed

No dose

adjustment

needed

Preferred add-

on (Lira- or

Sema-glutide) if

SGLT2i is con-

traindicated

1st choice preferred

add-on (Empa- or

Cana-gliflozin)

if eGFR is adequate

Efficacy

(↓A1c)

1 to 2%

High

1 to 1.5%

High

1 to 2%

High

1 to 1.5%

High

No “ceiling”

Highest

0.6 to 0.8%

Intermediate

0.5 to 1.6%

High

0.5-0.9% eGFR dependent

Intermediate to High

0.5% 0.4 to 0.5% 0.4 to 0.7% 0.4 to 0.6%

Low to Intermediate

Route Oral Oral Oral Oral SQ Oral SQ Oral Oral Oral Oral SQ

Other

benefits

Extensive

experience

DurabilityBenefit in NASH

↑ HDL

Extensive

experience

↓ Postmeal

glucose

excursions.

Universal

ResponseWell tolerated ↓ Postmeal

glucose

excursions.

↓ BP ↓ Postmeal

glucose

excursions.

↓LDL-C ↓ Postmeal

glucose

excursions.

Other

risks

Nausea

Diarrhea

Lactic

acidosis

B12 ↓

Edema

↑Fracture risk

? Bladder

cancer

? Macular

edema

Weight gain

High rate of

secondary

failure

Weight gain

Frequent

dosing

Weight gain Angioedema

Urticaria

? Pancreatitis

? Arthralgia

? Bullous

pemphigoid

Nausea

Vomiting

↑ Heart rate

?Pancreatitis

Medullary

thyroid cancer

in animals

GU tract infection

↑ K, Dehydration

Hypotension, DKA,

↑ LDL, ↑ Cr (brief)

↑ risk of

amputation/fracture

with Canagliflozin

Flatulence

Diarrhea

Frequent

dosing

Constipation

↑ Triglyceride

May ↓

absorption of

other

Medications

Orthostatic

hypotension

Syncope

Dizziness

Nausea, Fatigue

Rhinitis

Nausea

Vomiting

Frequent

dosing

Contra-

indication

eGFR <30

Acidosis

Hypoxia

Dehydration

NYHA III/IV

heart failureActive bladder

cancer

Hepatic

impairment

Severe renal

or hepatic

impairment

Use with

caution in

patients with a

h/o

pancreatitis.

PMH or FH of

MEN2/Medullary

thyroid cancer

Caution in h/o

pancreatitis or

gastroparesis.

Renal impairment(See above CKD+ row

and page 15)

Cirrhosis Inflammatory

bowel

disease

Intestinal

obstruction.

TG >500mg/dl

h/o of bowel

obstruction.

Hypertriglyceri

demia-induced

pancreatitis.

Severe

diabetic

gastroparesis

Pharmacological Therapy of Type 2 Diabetes : Comparison of Glucose-Lowering MedicationsUse this table to choose a class of medication – Consider the factors in first column, that will impact the medication choice.

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5

5 Major

groups

Insulin Sensitizers Insulin Providers GLP-1 (Glucagon-like Peptide-1)

-based therapy

Glucose

Absorption

Inhibitor

Others

(less popular)

12

Classes

Biguanide(Metformin)

Thiazolidi

-nedione

Insulin secretagogues Insulin DPP4

Inhibitors

GLP-1 Receptor

Agonists

SGLT2

Inhibitors

α Glucosi-

dase

Inhibitors

Bile Acid

Sequest-

rant

Dopamine-

2 Agonist

Amylin

MimeticsSulfonylurea Glinides

Currently

Available

Medications

(Brand name)

Metformin

(Glucophage,

Fortamet,

Glumetza)

Pioglitazone

(Actos)

Glipizide

(Glucoterol),

Glimeperide

(Amaryl),

Glyburide

(Micronase,

Diabeta,

Glynase)

Repaglinide

(Prandin),

Nateglinide

(Starlix)

Meal insulin:Novolog, Humalog

Apidra,

Humulin/Novolin R

Afrezza inhalor

Basal insulin:Lantus/Basaglar/

Toujeo/, Levemir,

Tresiba

Humulin/Novolin N

Sitagliptin

(Januvia),

Saxagliptin

(Onglyza),

Linagliptin

(Trajenta),

Alogliptin

(Nesina)

Exenatide

(Byetta,Bydureon),

Liraglutide (Victoza),

Lixisenatide (Adlyxin),

Dulaglutide (Trulicity)

Semaglutide (Ozempic)

Canagliflozin

(Invokana),

Dapagliflozin

(Farxiga),

Empagliflozin

(Jardiance)

Ertugliflozin

(Steglatro)

Acarbose(Precose),

Miglitol(Glyset)

Coleseve-

lam

(Welchol)

Bromocrip-

tine

(Cycloset)

Pramlin-

tide

(Symlin)

Minimum –

Maximum

dose

&

Dosing

Frequency

500mg qd-

1000 mg bid

Actos

15-45 mg qd

Glipizide

2.5-20 mg

bid/ac

Glimeperide

1- 8 mg qam

Glyburide1.25-20mg

qam

Prandin

0.5-4 mg

tid/ac

Starlix

60-120 mg

tid/ac

No maximum

dose

Januvia 25-100 mg qam

Onglyza

2.5-5 mg qam

Tradjenta

5 mg qam

Nesina6.25-25mg qam

All sq injections:

Byetta 5-10 mcg bid/ac

Victoza 0.6-1.8 mg qam

Adlyxin 10-20mcg qam

Bydureon or Bydureon

Bcise 2 mg qw

Trulicity 0.75-1.5 mg qw

Ozempic 0.25-1.0 mg

qw

Invokana

100-300 mg qam

Farxiga

5-10 mg qam

Jardiance

10-25 mg qam

Steglatro

5-15 mg qam

Precose or

Glycet

25-100 mg

tid/ac

625-1250

mg tid

0.8-4.8 mg

qamsq

injection

15-120

mcg

tid/ac

Available

strength

500, 850,

1000 mg

Actos

15, 30,

45 mg

Glipizide

5, 10 mg

Glimeperide

1, 2, 4 mg

Glyburide

1.25, 2.5, 5

mg

Prandin

0.5, 1, 2 mg

Starlix

60,120 mg

Pen:

3ml (300 Units)

Vial:

10ml (1000 Units)

Januvia

25,50,100 mg

Onglyza

2.5, 5 mg

Tradjenta

5 mg

Nesina6.25,12.5,25 mg

Byetta 5,10mcg

Victoza 0.6, 1.2, 1.8 mg

Adlyxin 10, 20mcg

Bydureon or Bydureon

Bcise 2 mg

Trulicity 0.75, 1.5 mg

Ozempic 0.25, 0.5, 1.0

mg

Invokana

100, 300 mg

Farxiga

5, 10 mg

Jardiance

10, 25 mg

Steglatro

5, 15mg

Precose or

Glycet

25,50,

100 mg

625 mg 0.8 mg 15, 120

mcg pen

Combination Metformin and TZD can be

used together.

Do not use Sulfonylurea and

Glinides together.

Do not use DPP4 inhibitors and GLP1 RA

together.

With meal

insulin only

Available

combination

(2-in-1)

medications

WITH ACTOS:

Actoplus Met XR (Actos+Metformin)15/1000, 30/1000mg qam (XR)

15/500, 15/850 mg bid (generic)

Duetact (Actos+Amaryl)

30/2, 30/4 mg qam

Oseni (Nesina+Actos)

(12.5 or 25) + (15 or 30 or 45 mg)

qam

WITH DPP4 inhibitor:

JanuMet XR (Januvia+metformin)

50/500, 50/1000, 100/1000 mg qam

Kombiglyze XR(Onglyza+metformin)

2.5/1000, 5/500, 5/1000 mg qam

Kazano (Nesina+metformin)

12.5/500, 12.5/1000 mg bid

Oseni (Nesina+Actos)

(12.5 or 25) + (15 or 30 or 45 mg) qam

Jentadueto (Tradjenta+metformin)

2.5/500, 2.5/850, 2.5/1000 mg bid

WITH a basal insulin:

Xultophy

Degludec (Tresiba) +

liraglutide (Victoza)

Soliqua

glargine (Lantus) +

lixisenatide (Adlyxin)

WITH SGLT2 inhibitor:

Invokamet XR (Invokana+metformin)50 or 150/500, 50 or 150/1000 mg qam

Xigduo XR (Farxiga+met)5 or 10/500, 5 or 10/1000 mg qam

Synjardy XR (Jardiance+met)5 or 10 or 12.5 or 25/1000 mg qam

Glyxambi (Jardiance+Tradjenta)10/5, 25/5 mg qam

Qtern (Farxiga+Onglyza)

10/5mg qam

Pharmacological Therapy of Type 2 Diabetes : Comparison of Glucose-Lowering Medications

Use this table to prescribe a medication from the class chosen in previous table6

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Insulin regimens Starting dose Titration

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7

Add GLP1 RA.Move to step 2 or 3 If A1c is not at goal.

• Once insulin is initiated, the physician should readjust the dose by 10-20% every 1-2 weeks and/or advise the patient to self-titrate the dose until BG targets are met.• For hypoglycemia, determine the cause and reduce the corresponding dose by at least 10-20%.

Basal insulin therapy:Start 0.2 Unit/kg body weight

or 10 units QHS.(Lantus/Toujeo/Basaglar, Levemir, Tresiba or NPH)

Basal+1 regimen: Add one dose of prandial insulin

before main meal of the day.Start 0.1 U/kg, 4 units or 10% of current basal dose. (Novolog, Fiasp, Humalog, Admelog, Apidra or Human insulin R)

For patients on basal insulin or basal+1 regimen:Add prandial insulin before each meal or tid/ac.

Start 0.1 U/kg, 4 units or 10% basal dose per meal

One injection dailywith a basal insulin

To cont’ metformin, GLP1 RA ± other non-insulin agents

Two injections dailywith Basal+1 regimen or

Pre-mixed insulin

To cont’ metformin. Consider stopping other non-insulin agents.

Multiple injections dailywith Basal Prandial Therapy

To cont’ metformin. Consider stopping other non-insulin agents.

Step 2

Step 3

Management of Type 2 Diabetes : Guide for Insulin Initiation and Titration

Patients may adjust the dose by 1 unit every night or by 3 units or 10-15% every 3 nights until target fasting

BG of 80-130 mg/dl is achieved.Consider adding prandial insulin if A1c is not at goal though the patient has been taking at least 0.7-1.0

unit/kg of basal insulin or fasting BG has been at goal.

Patients may adjust the prandial insulin dose by 1 unit every day or by 2 units or 10-15% every 3 days until 2 hours post-meal BG of 100-160 or next

pre-meal BG of 80-130 is achieved.

Patients may adjust the prandial insulin dose by 1 unit every day or by 2 units or 10-15% every 3 days

until 2 hours post-meal BG of 100-160 mg/dl or next pre-meal BG of 80-130 mg/dl is achieved.

Pre-mixed insulin therapy: Change basal insulin to pre-mixed insulin bid/ac. Divide current basal dose into ½ AM ½ PM or ⅔

AM ⅓ PM or Start 0.5 U/kg in 2 divided doses.

(Novolog 70/30, Humalog 75/25 or human insulin 70/30)

For patients on Pre-mixed insulin therapy: Use 80% of current total daily dose and give

50% as basal insulin + 50% as prandial insulin in 3 divided doses.

Breakfast dose: Patients may adjust the dose by 1 unit every day or

by 2 units or 10-15% every 3 daysuntil pre-dinner BG of 80-130 mg/dl is achieved.

Dinner dose:Patients may adjust the dose by 1 unit every day or

by 2 units or 10-15% every 3 daysuntil fasting BG of 80-130 mg/dl and/or bed-time BG of

130-180 mg/dl is achieved.Consider giving pre-mixed insulin tid/ac if bid/ac fails.

For insulin-naïve patients:Start total daily insulin dose of 0.5 U/kg and give 50% as

basal insulin + 50% as prandial insulin in 3 divided doses. orStart basal insulin 0.2 U/kg + prandial insulin 0.1 U/kg tid/ac

Step 1

Tips for successful insulin therapy

• NO SLIDING SCALE INSULIN• Start conservatively and adjust frequently• Maintain “50%-50% ratio” rule for basal and prandial insulin doses• Firstly, lower the fasting BG with the basal insulin.

– Consider adding prandial insulin when basal insulin dose is >0.7-1.0 U/Kg.– Adjust the dose frequently until the desired FASTING BG (usually 80-130) is achieved.

• Secondly, lower the post-meal BG with the prandial insulin.– Try to match carbohydrate amount and prandial insulin dose

• Fixed prandial insulin dose with consistent amount of carbohydrate (consider using a plate method)

• Flexible prandial insulin dose based on Insulin-to-Carbohydrate Ratio (ICR) (consider using a smart phone app for carb counter)

– Adjust the dose frequently until the desired 2-H post-meal BG (usually <160) or next pre-meal BG (usually 80-130) is achieved.

• Prandial insulin is for carbohydrate, and it should be given before a meal based on the meal (carbohydrate) size. Do not base on pre-dose BG level.– No meal no prandial insulin– Smaller meal lower dose of prandial insulin– Larger meal higher dose of prandial insulin

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2 ways to match carbohydrate amount and prandial insulin dose

1 injection dailywith a basal insulin

2 to 3 injections dailywith

“Basal+1” or “Basal+2” regimen

Multiple injections dailywith Basal Prandial Therapy

Step 1

Step 2

Step 3

Overview of Insulin Therapy (Advanced)To use together with next page # 10

Fixed prandial insulin dose before each meal and

consistent amount of carbohydrate (plate method)

Simple method

Flexible prandial insulin dose before each meal based on

Insulin-to-Carbohydrate Ratio (ICR) (see page 10)

Advanced method

Humulin R U-500 concentrated insulinbid/ac or tid/ac (see page 10)

Step 4Severe insulin resistance orhigh insulin dose (>150 Units daily)

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9

AddGLP-1 Receptor Agonist

to basal insulin

2 to 3 injections dailywith Pre-mixed insulin

bid/ac or tid/ac

Flexible prandial insulin dose before each meal based on

ICR and Insulin Sensitivity Factor (ISF) (see page 10)

INSULIN PUMP

10Supplement to "Overview of Insulin Therapy (Advanced)" at page 9

Patient’s weight in Lbs ICR ratio (carbohydrate in grams)

100-109 1:16 (1 unit insulin for 16 grams carb)








>200 1:8 (1 unit insulin for 8 grams carb)

Insulin-to-Carbohydrate Ratio (ICR) based on body weight in Lbs

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http://care.diabetesjournals.org/content/42/Supplement_1

STANDARD OF MEDICAL CAREIN DIABETES 2019


12


STANDARD OF MEDICAL CARE IN DIABETES 2019

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American Association of Clinical Endocrinologists : 2018 Comprehensive Type 2 Diabetes Management Algorithm13

https://www.aace.com/sites/all/files/diabetes-algorithm-executive-summary.pdf


14American Association of Clinical Endocrinologists : 2018 Comprehensive Type 2 Diabetes Management Algorithm

Naing/1-2019https://www.aace.com/sites/all/files/diabetes-algorithm-executive-summary.pdf


management of type 2 diabetes: non-insulin and insulin ......move to step 2 or 3 if a1c is not at...

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