Prevention Archives - Cardionerds

Prevention Archives - Cardionerds

By CardioNerdsMedicineHealth & FitnessMental HealthEducation
Download on the App Store

Prevention Archives - Cardionerds episodes

  • 367. GLP-1 Agonists: Clinical Implementation of GLP-1 Receptor Agonists with Dr. Neha Pagidapati

    CardioNerds (Drs. Gurleen Kaur and Richard Ferraro) and episode FIT Lead Dr. Spencer Carter (Cardiology Fellow at UT Southwestern) discuss the clinical implementation of GLP-1 receptor agonists with Dr. Neha Pagidapati (Faculty at Duke University School of Medicine). In this episode of the CardioNerds Cardiovascular Prevention Series, we discuss the clinical implementation of glucagon-like peptide-1 (GLP-1) receptor agonists. We cover the clinical indications, metabolic and cardiovascular benefits, and potential limitations of these emerging and exciting therapies. Show notes were drafted by Dr. Spencer Carter. Audio editing was performed by CardioNerds Academy Intern, student Dr. Pacey Wetstein.

    This episode was produced in collaboration with the American Society of Preventive Cardiology (ASPC) with independent medical education grant support from Novo Nordisk. See below for continuing medical education credit.

    Claim CME for this episode HERE.

    Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

    US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here.

    CardioNerds Prevention Page
    CardioNerds Episode Page
    CardioNerds Academy
    Cardionerds Healy Honor Roll

    CardioNerds Journal Club
    Subscribe to The Heartbeat Newsletter!
    Check out CardioNerds SWAG!
    Become a CardioNerds Patron!

    Pearls and Quotes – Clinical Implementation of GLP-1 Receptor Agonists
    1. GLP-1 agonists work through a variety of mechanisms to counteract metabolic disease. They increase insulin secretion, inhibit glucagon secretion, slow gastric motility, and increase satiety to limit excess energy intake.
    2. Patients with type II diabetes and an elevated risk for atherosclerotic cardiovascular disease should be considered for GLP-1 agonist therapy regardless of hemoglobin A1c.
    3. GLP-1 agonists offer significant ASCVD risk reduction even in the absence of diabetes. Newer data suggest a significant reduction in cardiovascular events with GLP-1 agonist therapy in patients who are overweight or obese and have a prior history of heart disease.
    4. GLP-1 agonists should generally be avoided in patients with a history of medullary thyroid cancer or MEN2. As these medications slow gastric emptying, relative contraindications include history of recurrent pancreatitis and gastroparesis.
    5. GLP-1 agonists should be initially prescribed at the lowest dose and slowly uptitrated to avoid gastrointestinal side effects.
      6. Show notes – Clinical Implementation of GLP-1 Receptor Agonists

      What were the groundbreaking findings of the STEP1 and SURMOUNT-1 trials and how these impact cardiovascular wellness?

      • The STEP1 and SURMOUNT trials demonstrated sustained clinically relevant reduction in body weight with semaglutide and tripeptide, respectively, in patients with overweight and obesity. As obesity is an important risk factor for the development of cardiovascular disease, weight reduction meaningfully contributes to cardiovascular wellness.

        • What were the findings of the LEADER trial and their implications for patients with type II diabetes and high cardiovascular risk?

        • The LEADER trial demonstrated a significant reduction in the rate of cardiovascular death, nonfatal MI, or nonfatal stroke in patients with type II diabetes treated with liraglutide. GLP-1 receptor agonist therapy should be considered in all patients with type II diabetes and elevated ASCVD risk regardless of A1c or current hyperglycemic therapy.

          • What are current indications for GLP1 agonists in the context of cardiometabolic disease.

          • GLP-1 receptor agonists should be considered in patients with type II diabetes and high ASCVD risk OR patients without diabetes who are overweight/obese and have a history of cardiovascular disease.

            • What are important side effects or contraindications to GLP1 agents when used for cardiovascular risk reduction and wellness?

            • GLP-1 receptor agonists should be avoided in patients with a history of medullary thyroid cancer or MEN2. Relative contraindications include recurrent pancreatitis, gastroparesis, or ongoing unexplained gastrointestinal symptoms.

              • What are practical concerns associated with GLP-1 use, and how can these be overcome?

              • Affordability and availability remain the leading practical limitations for GLP-1 receptor agonist therapies. Many insurance companies will cover semaglutide and tirzepatide for patients with diabetes. Obtaining coverage may be difficult otherwise, but this is an evolving field as more clinical trial data emerge. Beware of unauthentic/alternate formulations of these medications, as they tend not to be FDA-regulated and can pose health risks. Some patients express concern about injectable therapies, but GLP-1 injectors are typically very well tolerated and easy to use.
                • References – Clinical Implementation of GLP-1 Receptor Agonists
                • Brown, E., Heerspink, H. J., Cuthbertson, D. J., & Wilding, J. P. (2021). SGLT2 inhibitors and GLP-1 receptor agonists: established and emerging indications. The Lancet, 398(10296), 262-276.
                • https://www.sciencedirect.com/science/article/pii/S0140673621005365
                • Wilding, J. P., Batterham, R. L., Calanna, S., Davies, M., Van Gaal, L. F., Lingvay, I., … & Kushner, R. F. (2021). Once-weekly semaglutide in adults with overweight or obesity. New England Journal of Medicine.
                • https://www.nejm.org/doi/full/10.1056/NEJMoa2032183
                • Müller, T. D., Blüher, M., Tschöp, M. H., & DiMarchi, R. D. (2022). Anti-obesity drug discovery: advances and challenges. Nature Reviews Drug Discovery, 21(3), 201-223.
                • https://www.nature.com/articles/s41573-021-00337-8
                • Jastreboff, A. M., Aronne, L. J., Ahmad, N. N., Wharton, S., Connery, L., Alves, B., … & Stefanski, A. (2022). Tirzepatide once weekly for the treatment of obesity. New England Journal of Medicine, 387(3), 205-216.
                • https://www.nejm.org/doi/full/10.1056/NEJMoa2206038
                • Lincoff, M, Brown-Frandsen K, Colhoun H, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. (2023). 389(24):2221-2232.
                • https://www.nejm.org/doi/full/10.1056/NEJMoa2307563
                • Eberly, L, Yang L, Essien U, et al. (2021). Racial, ethnic, and socioeconomic inequities in glucagon-like-peptide-1 receptor agonist use among patients with diabetes in the US; 2(12):e214182.
                • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8796881/

                  • 44 min
                • 363. GLP-1 Agonists: Diving into the Data with Dr. Darren McGuire

                  Welcome back to the CardioNerds Cardiovascular Prevention Series, where we are continuing our discussion of Glucagon-like Peptide-1 Receptor Agonists (GLP-1 RAs). This class of medications is becoming a household name, not only for their implications for weight loss but also for their effect on cardiovascular disease. CardioNerds Dr. Ty Sweeney (CardioNerds Academy Faculty Member and incoming Cardiology Fellow at Boston Medical Center), Dr. Rick Ferraro (CardioNerds Academy House Faculty and Cardiology Fellow at Johns Hopkins Hospital), and special guest Dr. Franck Azobou (Cardiology Fellow at UT Southwestern) sat down with Dr. Darren McGuire (Cardiologist at UT Southwestern and Senior Editor of Diabetes and Vascular Disease Research) to discuss important trial data on GLP-1 RAs in patients with heart disease, as well as recent professional society guidelines on their use. Show notes were drafted by Dr. Ty Sweeney. Audio editing was performed by CardioNerds Intern student Dr. Diane Masket.

                  If you haven’t already, be sure to check out CardioNerds episode #350 where we discuss the basics and mechanism of action of GLP-1 RAs with Dr. Dennis Bruemmer.

                  This episode was produced in collaboration with the American Society of Preventive Cardiology (ASPC) with independent medical education grant support from Novo Nordisk. See below for continuing medical education credit.

                  Claim CME for this episode HERE.

                  Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

                  US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here.

                  CardioNerds Prevention Page
                  CardioNerds Episode Page
                  CardioNerds Academy
                  Cardionerds Healy Honor Roll

                  CardioNerds Journal Club
                  Subscribe to The Heartbeat Newsletter!
                  Check out CardioNerds SWAG!
                  Become a CardioNerds Patron!

                  Pearls and Quotes – GLP-1 Agonists: Diving into the Data
                  1. Patients with diabetes and clinical atherosclerotic cardiovascular disease (ASCVD) or who are at high risk of ASCVD benefit from treatment with a GLP-1 RA.
                  2. For persons with sufficient ASCVD risk and type 2 diabetes, GLP-1 RAs and SGLT2 inhibitors can, and often should, be used in combination. “Just like we don’t consider ‘and/or’ for the four pillars of guideline-directed medical therapy for heart failure with reduced ejection fraction, we shouldn’t parcel out these two therapeutic options…it should be both.”
                  3. Setting expectations with your patients regarding injection practices, side effects, and expected benefits can go a long way toward improving the patient experience with GLP-1 RAs.
                  4. Utilize a multidisciplinary approach when caring for patients on GLP-1 RAs. Build a team with your patient’s primary care provider, endocrinologist, clinical pharmacist, and nurse.
                  5. “This is really a cardiologist issue. These are no longer endocrinology or primary care drugs. We need to be prescribing them ourselves just like we did back in the nineties when we took over the statin prescriptions from the endocrinology domain…we need to lead the way.”
                    6. Show notes – GLP-1 Agonists: Diving into the Data

                    For which patients are GLP-1 RAs recommended to reduce the risk of major cardiac events?

                    • For patients with type 2 diabetes and ASCVD, starting a GLP-1 RA carries a Class 1, Level of Evidence A recommendation in the most recent ESC and ACC guidelines.
                    • For patients without diabetes or clinical ASCVD with an estimated 10-year risk of CVD exceeding 10%, consideration of starting a GLP-1 RA carries a Class 2b, Level of Evidence C recommendation to reduce CV risk.
                    • The STEP-HFpEF trial showed that among patients with obesity and HFpEF, once-weekly semaglutide may be beneficial in terms of weight loss and quality of life.
                    • The results of the FIGHT and LIVE trials question the utility and safety of liraglutide in treating patients with advanced HFrEF. Of the over 17,000 patients enrolled in the SELECT trial, about 25% had heart failure, of which about one-third had HFrEF. Stay tuned for sub-analyses from that trial for more info!

                      • Can we still prescribe GLP-1 Ras in patients with well-controlled T2DM?

                      • The recommendation to start GLP-1 RAs for cardiovascular benefit in eligible patients is made irrespective of HbA1C.
                      • If A1c is very low, or if the patient is experiencing episodes of hypoglycemia, consider backing off background diabetes therapy, especially if they don’t confer CV benefit.
                        • Note, the recent ESC guidelines recommending SGLT2i and GLP-1RA therapy do so irrespective of background metformin therapy. This is supported by the ADA Standards of Care in Diabetes.

                          • Is there evidence to suggest oral vs injectable GLP-1 RAs with respect to cardiac outcomes?

                          • The PIONEER-6 trial suggests cardiovascular benefit of oral semaglutide in patients with diabetes compared to placebo; however, the trial was only powered to assess safety.
                          • The ongoing SOUL trial is examining cardiovascular outcomes among patients being treated with oral semaglutide vs placebo with the primary outcome of time from randomization to the first occurrence of a major adverse CV event. Stay tuned!
                          • It is crucial that oral semaglutide be taken on an empty stomach, given its unique absorption and pharmacokinetics.

                            • What side effects can patients expect when initiating GLP-1 RAs?

                            • Nausea is common after starting these medications, but this generally ameliorates after 1-2 weeks of therapy.
                            • Setting expectations with your patients ahead of time can go a long way to improving adherence.
                            • We do not have dose-response data to say whether sub-maximal doses of GLP-1 RAs (for example, in patients who do not want or cannot tolerate the full dose) are effective. That said, the SELECT trial suggests the benefits of starting GLP-1 RAs begin early, even at introductory doses. Therefore, if a patient truly cannot tolerate higher doses, it may be reasonable to titrate slowly or hold at a lower dose.

                              • What does the literature say regarding the combined use of SGLT2 inhibitors and GLP-1 RAs?

                              • Sub-analyses examining the effect of background therapy when patients are randomized to receive the other vs. placebo suggest patients enjoy at least as good, if not better, outcomes from the combination of therapies.
                              • One of the first planned sub-analyses of SOUL will look at the potential additive effects of oral semaglutide alongside background SGLT2 inhibitor therapy.
                                • References – GLP-1 Agonists: Diving into the Data
                                • Marx N, Federici M, Schütt K, et al. 2023 ESC Guidelines for the management of cardiovascular disease in patients with diabetes: Developed by the task force on the management of cardiovascular disease in patients with diabetes of the European Society of Cardiology (ESC). European Heart Journal. 2023;44(39):4043-4140. https://academic.oup.com/eurheartj/article/44/39/4043/7238227?login=false
                                • Virani SS, Newby LK, Arnold SV, et al. 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. Circulation. 2023;148(9):e9-e119. https://www.ahajournals.org/doi/10.1161/CIR.0000000000001168
                                • ElSayed NA, Aleppo G, Aroda VR, et al. 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023. Diabetes Care. 2022;46(Supplement_1):S158-S190. https://diabetesjournals.org/care/article/46/Supplement_1/S158/148038/10-Cardiovascular-Disease-and-Risk-Management
                                • Husain M, Birkenfeld AL, Donsmark M, et al. Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. New England Journal of Medicine. 2019;381(9):841-851. https://www.nejm.org/doi/full/10.1056/NEJMoa1901118
                                • McGuire DK, Busui RP, Deanfield J, et al. Effects of oral semaglutide on cardiovascular outcomes in individuals with type 2 diabetes and established atherosclerotic cardiovascular disease and/or chronic kidney disease: Design and baseline characteristics of SOUL, a randomized trial. Diabetes Obes Metab. 2023;25(7):1932-1941. https://pubmed.ncbi.nlm.nih.gov/36945734/
                                • Kosiborod MN, Abildstrøm SZ, Borlaug BA, et al. Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity. N Engl J Med. 2023;389(12):1069-1084. https://pubmed.ncbi.nlm.nih.gov/37622681/
                                • Jorsal A, Kistorp C, Holmager P, et al. Effect of liraglutide, a glucagon-like peptide-1 analogue, on left ventricular function in stable chronic heart failure patients with and without diabetes (LIVE)-a multicentre, double-blind, randomised, placebo-controlled trial. Eur J Heart Fail. 2017;19(1):69-77. https://pubmed.ncbi.nlm.nih.gov/27790809/
                                • Margulies KB, Hernandez AF, Redfield MM, et al. Effects of Liraglutide on Clinical Stability Among Patients With Advanced Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial. JAMA. 2016;316(5):500-508. https://jamanetwork.com/journals/jama/article-abstract/2540402
                                  • 44 min

                                About Prevention Archives - Cardionerds

                                From the publisher's feed

                                A cardiology platform that aims to democratized cardiovascular education