Final Presentation for Block 6 Objectives: Describe the mechanism of action, side-effects and counseling points for GLP-1 RA Compare and contrast GLP-1 RA studies Discuss the PIONEER-6 study and its implications to clinical practice

1. GLP-1 RA and
Cardiovascular Outcomes
Sachpreet Bajaj, Pharm.D. Candidate 2020
VCU SOP

2. Learning Objectives
 Describe the mechanism of action, side-effects and
counseling points for GLP-1 RA
 Compare and contrast GLP-1 RA studies
 Discuss the PIONEER-6 study and its implications to
clinical practice

3. Mechanism of Action
Røder ME. Ther Adv Chronic Dis. 2018;9(1):33-50.

4. Cautions and Class Side Effects
 Gastrointestinal SE
 10-50%: Nausea, diarrhea, vomiting1
 Caution: gastroparesis
 Acute pancreatitis
 Incidence: 16 cases/14,562 patients2
 Injection site reactions
 10% GLP-1 agonists vs 1-5% insulin3
1.Shyangdan DS, et al. Cochrane Database Syst Rev. 2011;(10):CD006423.
2.Li L,, et al. BMJ. 2014;348:g2366.
3.Rosenstock J, et al. Diabetes Care. 2014;37(8):2317-25
Smaller meals or snacks
Rotate injection sites

5. GLP-1 RA Cardiovascular Outcomes Trials
Bain et al., Diabetes, Obesity and Metabolism, 2019; 21(3):499–508.
Bethel, M. et al., The Lancet Diabetes & Endocrinology. 2018;6(2):105–113.
Gerstein, H.C. et al., The Lancet. 2019;394(10193):121–130.

6. News Flash
What did the cardiovascular outcomes trial show
us about this oral drug?
https://www.fda.gov/news-events/press-announcements/fda-approves-first-oral-glp-1-treatment-type-2-diabetes

7. Bain et al., Diabetes, Obesity and Metabolism, 2019; 21(3):499–508.
Bethel, M. et al., The Lancet Diabetes & Endocrinology. 2018;6(2):105–113.
Gerstein, H.C. et al., The Lancet. 2019;394(10193):121–130.
Husain M, et al.. N Engl J Med. 2019; 381(9), 841-851

8. Rybelsus® in Clinical Practice?
Prescribing information
• Take at least 30 minutes
before the first food,
beverage, or other oral
medications of the day
with no more than 4 ounces
of plain water only
• Start with 3 mg once
daily for 30 days. After 30
days on the 3 mg dose,
increase the dose to 7 mg
once daily and 30 days on
7 mg to increase to 14 mg
if needed
https://www.novo-pi.com/rybelsus.pdf
Questions:
1. Benefit of oral semlaglutide
vs subcutaneous
semlaglutide?
2. Disadvantages?
3. Would you prescribe it?
4. Where in clinical therapy
would it fit?

10. What time is it?

11. Question 1
 Which GLP-1 RA study we covered today
concluded that liraglutide has cardiovascular
benefits (MACE-3) vs placebo?

12. Question 1 Answer
 LEADER trial
 13% reduction in primary outcome vs placebo

13. Question 2
 Due to the LEADER results, FDA approved an
indication for Victoza injection at what dose(s) to
reduce MACE-3 in T2DM and established
cardiovascular disease?

14. Question 2 Answer
 1.2 mg or 1.8 mg

15. Question 3
 What is the reason behind why Victoza’s initial
starting dose is 0.6 mg?

16. Question 3 Answer
 GI symptoms

17. Question 4
 Compared to SUSTAIN 6 (subQ semaglutide)
trial and PIONEER 6 (oral semaglutide) trial,
which MACE-3 outcome was statistically
significant for SUSTAIN 6 but not PIONEER 6?

18. Question 4 Answer
 Nonfatal stroke
SUSTAIN 6
PIONEER 6

19. Question 5
 Which study comprised of a large lower-risk
population (lower baseline A1C and lower
prevalence of established CVD) than other
trials?

20. Question 5 Answer
 REWIND Trial

21. Question 6
 For the PIONEER trial which primary outcome
was statistically significant?

22. Question 6 Answer

23. Question 7
 If a patient is taking Ozempic 0.5 mg subq and
wants to take Rybelsus, what dose(s) can you
start the patient on?

24. Question 7 Answer
 Rybelsus 7 mg or 14 mg

25. Question 8
 What BBW is on GLP-1 RA?

26. Question 8 Answer
 Thyroid C-cell tumor risk

27. Question 9
 What is one benefit (or side effect) of GLP-1
RA?

28. Question 9 Answer
 Weight loss
 1.5 to 2.5 kg over 30 weeks
Shyangdan DS, Royle P, Clar C, Sharma P, Waugh N, Snaith A. Glucagon-like peptide analogues for type 2 diabetes mellitus. Cochrane Database Syst Rev. 2011;(10):CD006423.