Obesity Management in Heart Failure: Best Practices to Date
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Neha Pagidipati, MD Duke University
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Obesity Management in Heart Failure: Best Practices to Date
- 1. Obesity Management in Heart Failure: Best Practices to Date Neha J. Pagidipati, MD MPH Associate Professor of Medicine, Duke University School of Medicine Director, Duke Cardiometabolic Prevention Clinic Associate Program Director, DCRI Research Fellowship Program Associate Faculty Director, DCRI Innovation Center
- 2. Disclosures • Research support from Alnylam, Amgen, Bayer, Boehringer Ingelheim, Eggland’s Best, Eli Lilly, Novartis, Novo Nordisk, Merck. • Consultation/Advisory Panels for Amgen, Bayer, Boehringer Ingelheim, CRISPR Therapeutics, Eli Lilly, Esperion, AstraZeneca, Merck, Novartis, and Novo Nordisk. • Executive Committee member for trials sponsored by Novo Nordisk and by Amgen. • DSMB for trials sponsored by J+J and Novartis. • Medical advisory board for Miga Health.
- 3. Do I need to prescribe AOMs?! We are increasingly learning that these are not just anti-obesity medications, they are CV risk reduction agents. STEP-HFpEF SELECT Kosiborod et al. NEJM 2023. DOI: 10.1056/NEJMoa2306963 Lincoff et al. N Engl J Med 2023;389:2221-2232.
- 4. The Older Generation of AOMs In general, I do not prescribe the older meds because of side effects or minimal efficacy: – Phentermine/topiramate (CI in Hypertension or any CVD) – Orlistat (GI side effects incl. fecal incontinence, moderate efficacy) – Naltrexone/bupropion (CI in uncontrolled Htn, lots of other side effects incl. tachycardia, moderate efficacy) – Lorcaserin: off the market for increased cancer risk
- 5. • How much you MOVE Move MORE • WHAT you eat: recommend combination of – Mediterranean Diet (heart health) – Low salt (hypertension) – Low carbohydrate (weight loss) • How MUCH you eat Eat LESS Always pair pharmacotherapy with lifestyle advice
- 6. Prescribing GLP1RAs for Obesity • Currently indicated for obesity and on the market: – Liraglutide 0.6-3mg SC daily – Semaglutide 0.25-2.4mg SC weekly – Tirzepatide 2.5-15mg SC weekly • Who is eligible? – BMI ≥ 30 OR BMI ≥ 27 with obesity-related comorbidity – Be cautious in patients with: Pancreatitis, gallbladder disease, chronic nausea/GI complaints, MEN2 or medullary thyroid cancer
- 7. Initiation, Titration, and Monitoring • Start at the lowest dose and titrate ~every 4 weeks – START LOW AND GO SLOW!! • Only titrate up if/when GI symptoms have resolved and if weight loss has reached a plateau • Monitoring: – If patient has not lost 4-5% of body weight after 12 weeks at max tolerated dose, consider stopping therapy
- 8. Potential Side Effects • Common: Nausea/vomiting (minimized by slow titration and small meals, improves with continued use) • Uncommon: Pancreatitis, Gallbladder events • Hypoglycemia: only in conjunction with SU or insulin • Increased heart rate (~5-6 bpm) • Injection site reaction
- 9. Adjusting Other Medications • If A1c is controlled AND on SU or insulin: – Replace SU with GLP1RA – Could lower insulin (by ~20%) or – better yet – ask PCP or endo to adjust • Stop DPP4i if taking
- 10. Instructions/Advice for Patients • Prefilled pens: Used to recommend YouTube videos (but now there’s too much junk); now recommend company websites • Nausea/vomiting (if occurs) will usually improve with continued use – the medicine slows gastric motility (and also promotes satiety!). • Eat small meals, eat slowly • Do not eat if you’re not hungry!!! • Strength training to avoid sarcopenia is important • Hold for 7 days prior to surgery
- 11. Duration of Therapy STEP 4 Trial Rubino et al. JAMA 2021
- 12. Duration of Therapy SURMOUNT 4 Trial Aronne et al. JAMA 2022
- 13. Coverage, Cost, and Access Issues • Biggest barriers to using GLP1RA AOMs: – Insurance coverage/cost • OOP Cost on GoodRx: – Saxenda: ~$1,300/month – Wegovy: ~$1,350/month – Zepbound: ~$1,060/month • Data on insurance coverage is minimal – Availability of drugs
- 15. Compounded GLP1RA – should I recommend to my patients? • NO!! • These substances are not FDA-approved • Many use the salt form of semaglutide (not the active ingredient in the drug) – no known safety or efficacy data for the salt form • FDA has previously reported “troubling conditions” in some compounding facilities https://www.fda.gov/drugs/human-drug-compounding/compounding-and-fda-questions-and-answers
- 17. Conclusions • GLP1ra AOMs fall under our scope of practice • Always pair AOMs with lifestyle advice • Start low and go slow!! • Biggest challenges are coverage, cost, and availability – Hopefully this will change soon! • Be cautious re: compounded AOMs
Editor's Notes
- Obesity and HF very common comorbidities; not just the case that HF pts develop obesity; obesity is also clearly related to the development of HF, and HFpEF in particular Pooled 4 cohorts Greater BMI and portended higher HFpEF risk compared with HFrEF, and this differential association was more pronounced in women than in men Obesity and related cardiometabolic traits including insulin resistance are more strongly associated with risk of future HFpEF versus HFrEF. The differential risk of HFpEF with obesity seems particularly pronounced among women and may underlie sex differences in HF subtypes.
- Not only are patients with obesity more likely to develop HF, they are more likely to die from it These are data from HFpEF in particular:
- How can obesity contribute to or worsen HF?
- This is specifically true for high-dose semaglutide, but many others have ongoing or planned CVOTs STEP-HFpEF: The mean change in the KCCQ-CSS was 16.6 points with semaglutide and 8.7 points with placebo (estimated difference, 7.8 points; 95% confidence interval [CI], 4.8 to 10.9; P<0.001), and the mean percentage change in body weight was −13.3% with semaglutide and −2.6% with placebo (estimated difference, −10.7 percentage points; 95% CI, −11.9 to −9.4; P<0.001). SELECT: 3p MACE
- When pts come to me for weight loss or we embark on that journey, I often don’t prescribe a med on the first visit – we focus first on lifestyle. Don’t make them “fail” lifestyle first, but I make sure I take the time to explain what they should be doing, and it’s hard to do that AND prescribe this new med in the same visit However much you’re moving, move MORE – discuss details (not a stroll, get HR up, don’t care about HR, talk but not sing) However much you’re eating, eat LESS (big to small plate; only 1 helping) Med diet: high in healthy fats and protein e.g…..; green leafy vegetables; moderate/low red meats, dairy, low sweets Low salt Low carb for weight loss; Med diet in and of itself is not a weight loss diet; need the low carb component to get you there; avoid bread, pasta, rice, cereal, sweets, potatoes, anything good
- This includes all permutations of GLP1RAs glucose-dependent insulinotropic peptide
- 338 participants, mean body weight change from baseline to 68 weeks was –15.8% with semaglutide vs –6.4% with liraglutide, a statistically significant difference
- Step 1: mean weight loss ~15%
- 2539 adults with a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 30 or more, or 27 or more and at least one weight-related complication, excluding diabetes, in a 1:1:1:1 ratio to receive once-weekly, subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo for 72 weeks, including a 20-week dose-escalation period. Second graph shows ITT
- Just like with medications for hypertension, hyperlipidemia, and diabetes – if you stop the medication, it no longer works and weight will go back up 803 participants completed a 20-week run-in of weekly treatment with subcutaneous semaglutide, 2.4 mg, with a mean weight loss of 10.6%, and were randomized to continued treatment with subcutaneous semaglutide vs placebo for an additional 48 weeks. At the end of this time, mean weight change was −7.9% vs +6.9%, respectively, a difference that was statistically significant.
- D/c after week 68
- After 36 weeks of open-label maximum tolerated dose of tirzepatide (10 or 15 mg), adults (n = 670) with obesity or overweight (without diabetes) experienced a mean weight reduction of 20.9%. From randomization (at week 36), those switched to placebo experienced a 14% weight regain and those continuing tirzepatide experienced an additional 5.5% weight reduction during the 52-week double-blind period.
- Looked for data on insurance coverage and it’s lacking – both b/c constantly shifting and b/c insurance companies don’t want to make that data public
- Treat and Reduce Obesity Act Unclear implications for Medicare budget
- The FDA reported it’s previously witnessed “troubling conditions” in some compounded facilities, including pet beds near sterile compounding areas, the use of toaster ovens for sterilization and people handling sterile drug products without skin protection, which can lead to the potential spread of bacteria. A 2013 study published in Drug R&D found compounded sterile preparations can pose the risk of microbial contamination. Over the course of 11 years, the study reports three separate cases of meningitis outbreaks were linked to “sterile” steroid injections contaminated with either bacteria or fungus made by compounding pharmacies. The U.S. faced its most brutal outbreak involving contaminated compounded drugs in 2012, when a Massachusetts pharmacy shipped drugs contaminated with fungus across the country. These drugs were injected into patients’ spines and joints, resulting in over 750 people in 20 states developing fungal infections, including 60 related deaths. Over 14,000 patients received injections from this batch of contaminated drug
- Main issue is access, but getting easier Initially there were production issues; seem to have gotten better; but now there are issues with competing access And who are we competing with?