Vanita R. Aroda, MD, prepared useful Practice Aids pertaining to type 2 diabetes mellitus for this CME activity titled “Test Your Knowledge: Current Guidance on GLP-1 Receptor Agonists to Individualize Treatment for T2DM.” For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at https://bit.ly/2WqxxYQ. CME credit will be available until June 24, 2021.

1. Managing Patients With Type 2 Diabetes Mellitus1,a
PRACTICE AID
Access the activity, “Test Your Knowledge: Current Guidance on GLP-1 Receptor Agonists to Individualize
Treatment for T2DM,” at PeerView.com/YEQ40
1. Assess Key Patient Characteristics
• Current lifestyle
• Comorbidities (ie, ASCVD, CKD, HF)
• Clinical characteristics (ie, age, A1C,
weight)
• Issues such as motivation and
depression
• Cultural and socioeconomic context
2. Consider Specific Factors
That Affect Choice of Treatment
• Individualize A1C target
Effect on weight and hypoglycemia
• Adverse event profile of medication
• Complexity of regimen (ie, frequency,
mode of administration)
• Choose regimen to optimize adherence
and persistence
• Access, cost, and availability of
medication
3. Shared Decision-Making to Create
a Management Plan
• Involves an educated and informed
patient (and their family/caregiver)
• Seeks patient preferences
• Effective consultation includes
motivational interviewing, goal setting,
and shared decision-making
• Empowers the patient
• Ensures access to DSMES
7. Review and Agree
on Management Plan
• Review management plan
• Mutual agreement on changes
• Ensure agreed upon modification of
therapy is implemented in a timely
fashion to avoid clinical inertia
• Decision cycle undertaken regularly
(at least once/twice a year)
6. Ongoing Monitoring and Support
• Emotional well-being
• Check tolerability of medication
• Monitor glycemic status
• Biofeedback including SMBG, weight,
step count, A1C, BP, and lipids
5. Implement Management Plan
• Patients not meeting goals generally
should be seen at least every 3
months as long as progress is made
• More frequent contact initially is often
desirable for DSMES
4. Agree on Management Plan
• Specify SMART goals
– Specific
– Measurable
– Achievable
– Realistic
– Time limited
Goals of Care
• Prevent
complications
• Optimize QOL
Patient-Centered Factors Affecting Treatment Choices
Start
here

2. Managing Patients With Type 2 Diabetes Mellitus1,a
PRACTICE AID
Access the activity, “Test Your Knowledge: Current Guidance on GLP-1 Receptor Agonists to Individualize
Treatment for T2DM,” at PeerView.com/YEQ40
First-line therapy is metformin and comprehensive lifestyle modifications (including weight management and physical activity)
Consider independently of baseline A1C
or individualized A1C target
ASCVD predominates
If A1C above target
HF or CKD predominates
If A1C above target
Indicators of high risk or established
ASCVD, CKD, or HF
Compelling need to minimize
hypoglycemia
If A1C above target
If A1C above target
If A1C above target
If A1C above target
If A1C above target
Cost is a major issue
If A1C above target
If A1C above target
To avoid
therapeutic inertia,
reassess and
modify treatment
regularlyNO
• Established ASCVD
• Indicators of high ASCVD
risk (age >55 years with
coronary, carotid, or lower
extremity artery stenosis
>50% or LVH)
Preferably
GLP-1 RA
with proven CVD benefit
or
SGLT2i with proven CVD benefit
if eGFR adequate
If further intensification is
required or patient is now unable
to tolerate GLP-1 RA and/or
SGLT2i, choose agents
demonstrating CV safety:
• For patients on GLP-1 RA,
considering adding SGLT2i
with proven CVD benefit;
DPP-4i if not on GLP-1 RA;
basal insulin; TZD; or SU
• Particularly HFrEF
(LVEF <45%)
• CKD: specifically eGFR
30-60 mL/min/1.73 m2
or UACR >30 mg/g,
particularly UACR >300 mg/g
Preferably
SGLT2i with evidence of reducing
HF/CKD progression in CVOTs if
eGFR adequate
or
If SGLT2i not tolerated/
contraindicated
or if eGFR less than adequate
add GLP-1 RA
with proven CVD benefit
Avoid TZD in the setting of HF;
choose agents demonstrating CV
safety: for patients on SGLT2i,
consider adding GLP-1 RA with
proven CVD benefit; DPP-4i
(not saxagliptin) in the setting
of HF (not on GLP-1 RA);
basal insulin; or SU
DPP-4i GLP-1 RA SGLT2i TZD
SGLT2i
or
TZD
SGLT2i
or
TZD
GLP-1 RA
or DPP-4i
or TZD
SGLT2i
or DPP-4i
or
GLP-1 RA
Continue with addition of other agents
as outlined above
Consider the addition
of SU or basal insulin:
• Choose later-generation SU with lower
risk of hypoglycemia
• Consider basal insulin with lower risk
of hypoglycemia
GLP-1 RA
with good efficacy
for weight loss
SGLT2i
SGLT2i
GLP-1 RA
with good efficacy
for weight loss
If quadruple therapy required, or SGLT2i
and/or GLP-1 RA not tolerated/
contraindicated, use regimen with
lowest risk of weight gain
Preferably
DPP-4i (if not on GLP-1 RAs)
based on weight neutrality
If DPP-4i not tolerated/contraindicated
or patient already on GLP-1 RA, cautious
addition of SU, TZD, or basal insulin
SU TZD
TZD SU
• Insulin therapy: basal insulin
with lowest acquisition cost
or
• Consider DPP-4i or SGLT2i
with lowest acquisition cost
ADA: Treatment Algorithm
YES
Compelling need to minimize
weight gain or promote weight loss
If A1C above individualized target
proceed as below

3. Managing Patients With Type 2 Diabetes Mellitus1,a
PRACTICE AID
a
These algorithms have been adapted from the original source; see full article for additional information on these recommendations.
ADA: American Diabetes Association; ASCVD: atherosclerotic cardiovascular disease; BP: blood pressure; CKD: chronic kidney disease; CVD: cardiovascular disease; CVOTs: cardiovascular outcomes trials; DPP-4i: dipeptidyl peptidase-4 inhibitor; DSMES: Diabetes Self-Management
Education and Support; eGFR: estimated glomerular filtration rate; FPG: fasting plasma glucose; HFrEF: heart failure with reduced ejection fraction; LVEF: left ventricular ejection fraction; LVH: left ventricular hypertrophy; NPH: neutral protamine Hagedorn; SGLT2i: sodium-glucose
cotransporter 2 inhibitor; SMBG: self-monitored blood glucose; SU: sulfonylurea; TZD: thiazolidinediones; UACR: urine albumin-to-creatinine ratio.
1. American Diabetes Association. Diabetes Care. 2020;43(suppl 1):s1-s212.
Access the activity, “Test Your Knowledge: Current Guidance on GLP-1 Receptor Agonists to Individualize
Treatment for T2DM,” at PeerView.com/YEQ40
To avoid clinical inertia reassess
and modify treatment regularly (3-6 months)
ADA: Injectable Therapy Treatment Algorithm
Consider GLP-1 RA in most patients prior to insulin
INITIATION:Initiate appropriate starting dose for agent selected (varies within class)
TITRATION:Gradual titration to maintenance dose (varies within class)
If injectable therapy is needed to reduce A1C
Add basal insulin
Choice of basal insulin should be based on patient-specific considerations, including cost
Add basal analog or bedtime NPH insulin
INITIATION:Start 10 IU a day or 0.1-2.0 IU/kg a day
TITRATION:
• Set up FPG target
• Choose evidence-based titration algorithm (eg, increase 2 units every 3 days to reach FPG target without
hypoglycemia)
• For hypoglycemia, determine cause; if no clear reason, lower dose by 10%-20%
Add prandial insulin
Usually one dose with the largest meal or meal with greatest FPG excursion; prandial insulin can be
dosed individually or mixed with NPH as appropriate
INITIATION:
• 4 IU a day or 10% of basal insulin dose
• If A1C <8% (64 mmol/mol) consider lowering the basal dose by 4
IU a day or 10% of basal dose
TITRATION:
• Increase dose by 1-2 IU or 10%-15% twice weekly
• For hypoglycemia, determine cause; if no clear cause lower
corresponding dose by 10%-20%
If above A1C target
If already on GLP-1 RA or if GLP-1 RA
not appropriate or insulin preferred
If above A1C target
despite adequately titrated basal analog or bedtime NPH or once basal dose >0.5 IU/kg or FPG at target
If on bedtime NPH, consider converting to twice-daily NPH regimen
INITIATION:Total dose = 80% of current bedtime dose; two-thirds given in the
morning and one-third given at bedtime
TITRATION:Titrate based on individualized needs
If above A1C target
Proceed to full basal-bolus regimen
(ie, basal insulin and prandial insulin with each meal)
Stepwise additional injections of prandial insulin
(ie, two, then three additional injections) Consider self-mixed/split insulin regimen
INITIATION:Total NPH dose = 80% of current NPH dose; two-thirds given before breakfast, one-third
TITRATION:Titrate each component of the regimen based on individualized needs
Consider twice daily premix insulin regimen
INITIATION:Usually unit per unit at the same total insulin dose, but may
TITRATION:Titrate based on individualized needs
If above A1C target
given before dinner; add 4 IU of short/rapid-acting insulin to each injection or 10% of reduced NPH dose require adjustment to individual needs

4. Counseling Patients About Treatments
for Type 2 Diabetes Mellitus (T2DM)
PRACTICE AID
Access the activity, “Test Your Knowledge: Current Guidance on GLP-1 Receptor Agonists to Individualize
Treatment for T2DM,” at PeerView.com/YEQ40
How effective at reducing BG?
Might prevent heart attacks?
Might increase the risk of HF?
Might slow the loss of renal function?
Suppresses appetite?
Might cause weight loss?
Hypoglycemia is a common AE?
Nausea is a common AE?
Administered as an injection?
Can be given once weekly?
Generic available?
Highly
Some do
No
Some may
Yes
Yes
No
Yes
Usually
Some can
Not yet
Highly
No
No
No
No
No
Yes
No
Always
No
Not yet
Highly
No
No
No
No
No
Yes
No
Never
No
Yes
Highly
Some might
Yes
No
No
No
No
No
Never
No
Yes
Moderately
Some do
No
Some may
No
Yes
No
No
Never
No
Not yet
Moderately
No
Some do
No
No
No
No
No
Never
No
Not yet
Characteristic
GLP-1 RAs
Basal
insulin DPP-4is SGLT2is TZDs SUs
Adverse Events Associated With T2DM Treatments1,2

5. Counseling Patients About Treatments
for Type 2 Diabetes Mellitus (T2DM)
PRACTICE AID
Access the activity, “Test Your Knowledge: Current Guidance on GLP-1 Receptor Agonists to Individualize
Treatment for T2DM,” at PeerView.com/YEQ40
• Twice-daily
injection
• 60 minutes
before
morning
and
evening
meals
Exenatide
BID
Liraglutide
• Daily
injection
• Any time
of day
Lixisenatide
• Daily
injection
• 60 minutes
before first
meal of the
day
Semaglutide
(oral)
• Daily oral
tablet
• 30 minutes
before
morning
meal
GLP-1 RAs: Frequency of Administration and Dosing With Respect to Meals2-6
Dulaglutide
• Weekly
injection
• Any time
of the day
Exenatide
ER
• Weekly
injection
• Any time
of day
Semaglutide
(injectable)
• Weekly
injection
• Any time
of day
Shorter-acting agents Longer-acting agents

6. Counseling Patients About Treatments
for Type 2 Diabetes Mellitus (T2DM)
a
Initial dose is intended to decrease GI-related AEs only, it does not provide effective glycemic control.
BG: blood glucose; BID: twice daily; ER: extended release; GLP-1 RAs: glucagon-like peptide-1 receptor agonists; IR: immediate release; SGLT2is: sodium glucose cotransporter 2 inhibitors; SUs: sulfonylureas; TZDs: thiazolidinediones.
1. American Diabetes Association. Diabetes Care. 2020;43(suppl 1):S1-S212. 2. https://www.accessdata.fda.gov/scripts/cder/daf/. 3. Hinnen D. Diabetes Spectr. 2017;30:202-210. 4. Abd El Aziz MS et al. Diabetes Obes Metab. 2017;19:216-227.
5. Kalra S et al. Diabetes Ther. 2019;10:1645-1717. 6. Bain SC et al. Diabetes Obes Metab. 2019;21:499-508.
PRACTICE AID
Access the activity, “Test Your Knowledge: Current Guidance on GLP-1 Receptor Agonists to Individualize
Treatment for T2DM,” at PeerView.com/YEQ40
GLP-1 RAs: Practical Aspects2
Frequency
Starting dose
Next higher dose
Next higher dose
Screw on needle
Separate prescription
for needle
Autoinjector
Daily
10 mcg
20 mcg
—
—
Lixisenatide
Daily
3 mga
7 mg
14 mg
—
—
—
Semaglutide
(oral)
Auto Tray
/pen
Weekly
2 mg
— —
— —
—
— —
—
Exenatide
ER
Twice daily
5 mcg
10 mcg
—
—
Exenatide
BID
Daily
0.6 mga
1.2 mg
1.8 mg
—
Liraglutide
Weekly
0.75 mg
1.5 mg
—
—
—
Dulaglutide
Weekly
0.25 mga
0.5 mg
1.0 mg
—
—
Semaglutide
(injectable)
= FDA
indication for
CV risk reduction

7. GLP-1 RAs: Prescribing Information Highlights1
PRACTICE AID
Access the activity, “Test Your Knowledge: Current Guidance on GLP-1 Receptor Agonists to Individualize
Treatment for T2DM,” at PeerView.com/YEQ40
Adjunct to diet and
exercise to improve
glycemic control in
adults with T2DM
Adjunct to diet and
exercise to improve
control in patients
aged ≥10 years
Reduce risk of MACE
in adults with T2DM
and established CVD
Reduce risk of MACE
in adults with T2DM
and CV risk factors
Exenatide
BID
Liraglutide DulaglutideLixisenatide
Semaglutide
(oral)
Exenatide
ER
Semaglutide
(injectable)
Indications

8. GLP-1 RAs: Prescribing Information Highlights1
PRACTICE AID
Access the activity, “Test Your Knowledge: Current Guidance on GLP-1 Receptor Agonists to Individualize
Treatment for T2DM,” at PeerView.com/YEQ40
Do not use in patients
with a history of
hypersensitivity to
this agent or any
product components
Personal or family
history of MTC or
patients with MEN2
History of drug-
induced immune-
mediated
thrombocytopenia
from exenatide
products
Exenatide
BID
Liraglutide DulaglutideLixisenatide
Semaglutide
(oral)
Exenatide
ER
Semaglutide
(injectable)
Contraindications

9. GLP-1 RAs: Prescribing Information Highlights1
a
Liraglutide is currently the only GLP-1 RA with a pediatric indication from the US FDA. b
Should not be used in patients with severe renal impairment. c
Should not be used in patients with end-stage renal disease. d
Not recommended in patients with end-stage renal disease.
e
Not recommended for use in patients with eGFR <45 mL/min/1.73m2
.
AKI: acute kidney injury; CVD: cardiovascular disease; DR: diabetic retinopathy; ER: extended release; GLP-1 RAs: glucagon-like peptide-1 receptor agonists; MACE: major adverse cardiovascular events; MEN2: multiple endocrine neoplasia type 2;
MTC: medullary thyroid carcinoma; T2DM: type 2 diabetes.
1. https://www.accessdata.fda.gov/scripts/cder/daf/.
PRACTICE AID
Access the activity, “Test Your Knowledge: Current Guidance on GLP-1 Receptor Agonists to Individualize
Treatment for T2DM,” at PeerView.com/YEQ40
Exenatide
BID
Liraglutide DulaglutideLixisenatide
Semaglutide
(oral)
Exenatide
ER
Semaglutide
(injectable)
Warnings
and Precautions
Pancreatitis
Hypoglycemia with insulin
secretagogue or insulin
Hypoglycemia in pediatric patients,
regardless of other agents
Hypersensitivity, including
anaphylaxis, angioedema
AKI or caution in patients with
renal impairment
Severe GI disease
(not studied)
Diabetic retinopathy (monitor
patients with history of DR)
Drug-induced immune-
mediated thrombocytopenia
Immunogenicity
Injection-site reactions
Acute gallbladder disease
edb,c
Thyroid C-cell tumors
(boxed warning)
a