Comparing the efficacy of an oral GLP-1 receptor antagonist with SGLT2 inhibitor. Results from the PIONEER-2 trial are applied to a patient case discussing diabetes management.

1. ORAL GLP-1 RAVS. SGLT2 INHIBITOR – A PATIENT CASE
¡ Derek Ruzzo
¡ 10/25/21

2. OBJECTIVES
Establish patient’s chief complaint Evaluate current medications, labs,
and systems
Implement action plan in conjunction
with patient and provider

3. PATIENT SS
CC
¡ “I feel the urge to urinate frequently
throughout the day and night. I’m also
quite thirsty even when I’m not doing
any sort of strenuous activity. I want
any adjustments to be as convenient
for me as possible.”
¡ 61-year-old male who urinates
frequently and experiences increased
thirst
¡ Feels lethargic throughout the day
¡ Diagnosed with T2DM in January 2020
¡ Delayed follow up with provider due
to COVID-19, but has since been
diligent about his appointments

4. BACKGROUND INFORMATION
¡ PMH
¡ Asthma (intermittent)
¡ HTN (diagnosed 2007)
¡ T2DM (diagnosed 2020)
¡ Dyslipidemia
¡ Osteoarthritis
¡ FH
¡ Father (84) alive and well, Mother (83) alive and
well, both parents have HTN, dyslipidemia, and
arthritis
¡ SH
¡ Married x 35 years with 3 adult children
¡ Works full time
¡ Drinks approx. 2 alcoholic beverages/week
(usually on the weekend)
¡ Denies tobacco and elicit drug use
¡ Minimal caffeine consumption à pt states they
are not a coffee drinker
¡ Walks approx. 2 miles around neighborhood 5
days per week

5. PHYSICAL EXAM & VITALS (9/15/21)
¡ BP: 126/80 mmHg
¡ HR: 71 BPM
¡ Wt: 196 lbs (89 kg)
¡ Ht: 5’8” (172.7 cm)
¡ RR: 13
¡ Temp: 98.2
¡ Pain Scale: 0/10

6. ROS (9/15/21)
¡ AOx3
¡ HEENT: unremarkable
¡ Neck: unremarkable
¡ Abdomen: unremarkable
¡ Cardiac: unremarkable
¡ Extremities: unremarkable
¡ GI: unremarkable
¡ Genitourinary: unremarkable
¡ Psych: unremarkable
¡ Respiratory: unremarkable
¡ Musculoskeletal: unremarkable
¡ Endocrine: polydipsia, polyuria

7. LABS (4/15/21)
Tests LabValues
Glucose 152 mg/dL
A1c 7.7%
Total Cholesterol 218 mg/dL
HDL 47 mg/dL
LDL 140 mg/dL
Triglyceride 184 mg/dL
Laboratory
Data

8. MEDICATION LIST
Drug Dose Frequency Indication
Benicar (olmesartan) 40 mg Daily BP
labetalol 200 mg Daily BP/HR
metformin 1000 mg BID T2DM
ProAir HFA 1-2 puffs Q4-6H PRN Asthma
atorvastatin 20 mg Daily Cholesterol
Voltaren 1% gel 2 g (affected joints) PRN Osteoarthritis
Tylenol Arthritis 1300 mg (2 caps) Q8H PRN Osteoarthritis
Allergies: PCN à hives

9. 10 -YEAR ASCVD RISK
¡ White
¡ Male
¡ Age: 61
¡ Lipid panel
¡ T2DM
¡ HTN treatment
ASCVD risk = 21.7%

10. PROBLEM LIST
LIPIDS Decrease TC, LDL,TG
T2DM
Lower fasting blood glucose to goal (80-130 mg/dL)2
Lower A1c to goal (<7%)2

11. Managing T2DM1

12. MANAGING T2DM
¡ 1st line: metformin 1000 mg PO BID / lifestyle
modifications1
¡ A1c above goal + ASCVD risk factors: Add GLP-1 RA
or SGLT2i1

13. PIONEER 2 TRIAL2
¡ Randomized, open label, multi-national, 52-week study
¡ 1:1 randomization
¡ Compared PO semaglutide vs empagliflozin
¡ Primary endpoint à change in A1c from baseline to week 26
¡ Secondary endpoint à change in A1c and body weight from baseline to week 52

14. PIONEER 2 TRIAL (CONT.)
¡ Eligibility:
¡ adults with T2DM
¡ A1c of 7-10.5%
¡ stable metformin dose (> 1500 mg daily
or max tolerable dose)
¡ Exclusions:
¡ diabetic or obesity medication other than
metformin within previous 90 days
¡ short term insulin (< 14 days)
¡ eGFR < 60
¡ retinopathy
¡ maculopathy

15. PIONEER 2 TRIAL (RESULTS)
Primary and Secondary Endpoints
Baseline characteristics/demographics
PO
semaglutide
empagliflozin
Age, mean 57 58
Female, n (%) 205 (49.9) 201 (49)
A1c, mean % 8.1 8.1
PO
semaglutide
(n = 412)
empagliflozin
(n = 410)
A1c week 26 -1.4% -0.9%
A1c week 52 -1.3% -0.8%
body wt. (kg) -3.8% -3.7%
Results: PO semaglutide is superior to empagliflozin at reducing A1c at 26 weeks. A significant
difference remained at 52 weeks (95% CI -0.6, -0.3, p < 0.005)2

16. PIONEER 2 TRIAL (CONT.)
Adverse Events
¡ Similar between both groups
¡ Most mild-moderate
¡ Nausea most frequent in PO semaglutide group
¡ Male and female genital infections (mild-
moderate) more frequent in empagliflozin
group vs. PO semaglutide group (6.7% and 8.5%
vs. 0% and 2.0%, respectively)
Study Critiques
¡ Two estimands: treatment policy and trial product
¡ Confounding variable: additional antidiabetic
medication prescribed at the investigator’s discretion
(excluding GLP-1RAs, DPP4 inhibitors, amylin
analogs, and SGLT2i)

17. SS AND T2DM
¡ SS currently taking metformin 1000 mg PO BID monotherapy
¡ Fasting blood glucose & A1c not at goal
¡ Qualifies for additional anti-diabetic therapy based on ADA treatment guidelines
¡ GLP-1 RA or SGLT2i beneficial due to ASCVD risk or wt. loss
¡ All labs within normal limits excluding glucose and lipids
¡ SS on moderate intensity statin therapy
¡ BP well controlled on current ARB and BB therapy

18. ASSESSMENT
¡ SS has T2DM and is experiencing polyuria, polydipsia and lethargy
¡ His treatment goals are to resolve these symptoms and bring glucose levels and A1c
to target
¡ metformin monotherapy not achieving A1c < 7% à adjunct therapy necessary
¡ SS can benefit from GLP-1 RA or SGLT2i to lower A1c to goal
¡ No CIs to either class of drugs
¡ Glucose levels should be re-evaluated at least 2 weeks after initiation of adjunctive
therapy à approx. 3 months for A1c

19. PLAN (PRIMARY PROBLEM)
¡ Continue metformin 1000 mg PO BID
¡ Initiate Rybelsus (semaglutide) 3 mg PO
daily for 30 days à increase to 7 mg PO
daily à further increase to 14 mg PO daily
if glycemic goals not met
¡ Educate SS that 3 mg dose is to reduce GI
symptoms à not effective for glycemic
control
¡ Alert SS of potential side effects: diarrhea,
constipation, stomach pain, upset stomach,
vomiting
¡ Take medication 30 mins prior to food,
drink and other meds
¡ Take with no more than 4 oz (120 mL) of
plain water
¡ Encourage healthy eating habits and
exercise
¡ Explain the importance of SMBG
¡ Discuss benefits of CGM

20. LIPID LOWERING
¡ SS currently on atorvastatin 20 mg daily (moderate intensity) à increase to atorvastatin 40
mg daily (high intensity)
¡ Educate SS on common side effects (myopathy) with statin therapy
¡ Target LDL < 70
¡ Consider adding ezetimibe if cholesterol levels are not met
¡ Continue to encourage healthy diet and exercise
¡ TG lowering therapy not indicated at this time
¡ omega-3 à TG > 500
¡ fibrates à TG > 1000
TC = 200 mg/dL
LDL = 140mg/dL
TG = 184 mg/dL
HDL = 49 mg/dL

21. REFERENCES
1. American Diabetes Association. (2021). 9.
Pharmacologic approaches to glycemic treatment:
Standards of Medical Care in diabetes-2021. Diabetes
Care, 44(Suppl 1), S111–S124.
2. Rodbard, H.W., Rosenstock, J., Canani, L. H.,
Deerochanawong, C., Gumprecht, J., Lindberg, S. Ø., et
al. PIONEER 2 Investigators. (2019). Oral semaglutide
versus empagliflozin in patients with type 2 diabetes
uncontrolled on metformin:The PIONEER 2
trial. Diabetes Care, 42(12), 2272–2281.
3. Lexicomp. 2021.

22. QUESTIONS