2025 ACC Concise Clinical Guidance: Medical Weight Management for Cardiovascular Health

Authors, Journal, Affiliations, Type, DOI

• Authors: Olivia Gilbert MD MSc FACC (Chair), Martha Gulati MD MS FACC (Vice Chair), Ty J. Gluckman MD MHA FACC; Writing committee: Kittleson MM, Rikhi R, Saseen JJ, Tchang BG, Hendel R, Krittanawong C, Kumbhani DJ, Wiggins B, Coylewright M
• Journal: Journal of the American College of Cardiology (JACC), Vol. 86, No. 7, August 19, 2025: 536–555
• Affiliations: ACC Solution Set Oversight Committee, American College of Cardiology
• Type: Concise Clinical Guidance (CCG) / Expert Consensus Statement; approved by ACC Clinical Policy Approval Committee May 2025
• DOI: https://doi.org/10.1016/j.jacc.2025.05.024

Overview

This ACC Expert Consensus Statement provides cardiologists with practical guidance for medically managing obesity using agents with proven cardiovascular benefit. Obesity (BMI ≥30 kg/m²) affects >1 billion adults worldwide and 40.3% of US adults; it is an independent CVD risk factor associated with HFpEF, AF, SCD, ASCVD, and VTE. The document positions nutrient-stimulated hormone (NuSH) therapies — liraglutide, semaglutide, and tirzepatide — as the preferred obesity pharmacotherapy for CV patients, citing their superior efficacy versus lifestyle intervention and more favorable risk profile than bariatric surgery. Critically, the guidance states patients should NOT be required to "try and fail" lifestyle intervention before initiating pharmacotherapy, and emphasizes long-term continuation as the default plan.

Keywords

Obesity, cardiovascular disease, weight management, GLP-1 receptor agonist, NuSH therapy, semaglutide, tirzepatide, liraglutide, HFpEF, SELECT trial, cardiovascular outcomes

Key Takeaways

Epidemiology and Definitions

• Obesity affects >1 billion adults globally; prevalence doubled in adults and quadrupled in children/adolescents over 3 decades
• US: 40.3% of adults have obesity (BMI ≥30 kg/m²); 9.4% have severe obesity (BMI ≥40 kg/m²)
• Severe obesity associated with reduced life expectancy: 9.1 years in men, 7.7 years in women
• Obesity is an independent CVD risk factor; associated with ASCVD, HFpEF, AF, SCD, VTE, and valvular disease
• BMI has significant limitations for individuals: does not account for fat distribution, muscle mass, sex, or racial differences
• Asian-specific (South Asian/Chinese) thresholds: overweight ≥23 kg/m²; obesity ≥25 kg/m²
• Waist circumference and waist-to-height ratio better predict central adiposity and CVD events

NuSH Therapy Framework

• NuSH (nutrient-stimulated hormone) therapies = broad category acting on metabolic pathways and appetite control; currently FDA-approved NuSH agents: GLP-1 RAs (liraglutide, semaglutide) and dual GLP-1/GIP RA (tirzepatide)
• NuSH therapies fill the treatment gap between insufficient lifestyle therapy and invasive bariatric surgery
• Target hormonal pathways controlling appetite (hunger, satiety, satiation, cravings)
• Titratable dosing allows individualized care

Weight Loss Thresholds for CV Outcomes

• ≥5% weight loss: improved triglycerides, fasting glucose, and systolic BP; prevention of incident disease
• 10–15% weight loss: CVD risk reduction
• >15% weight loss: CV mortality reduction and HFpEF adverse outcome reduction
• Lifestyle interventions alone have NOT been associated with reduction in adverse cardiovascular outcomes in RCTs (e.g., Look AHEAD)
• Bariatric surgery achieves substantial weight loss and reduced CVD events but often undesired by patients

NuSH Therapy Eligibility

• BMI ≥30 kg/m² (obesity) OR BMI ≥27 kg/m² with weight-related comorbidity
• Lifetime high BMI (not current BMI) may be used to establish eligibility — consistent with treating obesity as chronic disease
• Patients should NOT be required to "try and fail" lifestyle intervention before pharmacotherapy
• Lifestyle interventions should always be offered alongside NuSH therapies

Pharmacological Options

Liraglutide (Victoza/Saxenda)

• GLP-1 receptor agonist; once-daily SC injection
• Dosing: start 0.6 mg SC daily → increase weekly → 3 mg maintenance
• SCALE trial (56-week, n=3,731): weight ↓8.0% liraglutide vs ↓2.6% placebo; ≥5% weight loss: 63.2% vs 27.1%
• LEADER CVOT (T2DM high CV risk, n=9,340, 3.8yr): MACE HR 0.87 (95% CI 0.78–0.97) — first GLP-1 RA CVOT to show superiority

Semaglutide (Ozempic/Wegovy)

• GLP-1 receptor agonist; once-weekly SC injection
• Dosing: start 0.25 mg SC weekly → increase every 4 weeks → 1.7 or 2.4 mg maintenance
• STEP-1 trial (68-week, n=1,961): weight ↓14.9% semaglutide vs ↓2.4% placebo; ≥5% weight loss: 86.4% vs 31.5%
• SUSTAIN-6 (T2DM high CV risk, n=3,297, 2.1yr): MACE HR 0.74 (95% CI 0.58–0.95)
• SELECT (CVD + BMI >27 kg/m², NO T2DM, n=17,604, 3.3yr): MACE HR 0.80 (95% CI 0.72–0.90); weight ↓9.1 kg; HF hospitalization HR 0.79 NS — first trial demonstrating MACE benefit in obesity + CVD without T2DM

Tirzepatide (Mounjaro/Zepbound)

• Dual GLP-1 + GIP receptor agonist; once-weekly SC injection
• Dosing: start 2.5 mg SC weekly → increase every 4 weeks → 5, 10, or 15 mg maintenance
• SURMOUNT-1 trial (72-week, n=2,539): weight ↓15.0% (5 mg), ↓19.5% (10 mg), ↓20.9% (15 mg) vs ↓3.1% placebo; ≥5% weight loss: 85–91% vs 35%
• SUMMIT (HFpEF + obesity, n=731, 104 weeks): CV death/worsening HF HR 0.62 (95% CI 0.41–0.95; P=0.026) — first hard composite outcome benefit in obesity-HFpEF; KCCQ +6.9 pts; weight ↓13.9%
• SURPASS-CVOT (T2DM + CVD, ongoing; tirzepatide vs dulaglutide): estimated completion 2025
• SURMOUNT-MMO (CVD or risk + BMI ≥27 kg/m², n=15,374, ongoing): estimated completion 2027

Drug Selection

• Semaglutide and tirzepatide are the obesity medications of choice (highest efficacy)
• Tirzepatide achieves slightly greater weight loss than semaglutide (real-world + RCT data)
• Insurance coverage, availability, and affordability likely to dictate agent selection

Contraindications (all NuSH therapies)

• Personal/family history of medullary thyroid carcinoma (MTC)
• Multiple endocrine neoplasia syndrome type 2 (MEN2)
• Hypersensitivity to product or excipients
• Cautions: acute pancreatitis, acute gallbladder disease, hypoglycemia, renal impairment, suicidal behavior/ideation
• Screening thyroid ultrasound NOT required prior to initiation

Implications on Comorbidities (Table 4 Framework)

• Cardiology: de-escalate antihypertensives (avoid low BP); de-escalate diuretics in HF (avoid intravascular depletion)
• Endocrinology: re-check TSH at 10% weight loss (levothyroxine may be weight-based); reduce T2DM medications to avoid hypoglycemia
• Nephrology: adjust hemodialysis protocol and dry weight
• Gastroenterology: no data supporting stopping GLP-1 RA before elective upper endoscopy; adjust bowel prep; ursodiol consideration in cholelithiasis (higher gallbladder disorder risk on NuSH)
• Surgery/anesthesia: GLP-1 RA may be continued pre-operatively in patients without elevated risk of delayed gastric emptying; if held, 1 week may be considered
• Obstetrics: stop weekly NuSH therapies ≥2 months before conception; tirzepatide may reduce efficacy of some contraceptive agents
• Geriatrics: caution with excess weight loss and sarcopenia/frailty risk; re-evaluate medications to reduce polypharmacy

General Treatment Principles

• Long-term treatment is the default plan; weight regain expected after discontinuation
• Discontinuation should not occur unless determined by patient and/or clinician
• Compounded NuSH therapies discouraged: risk of dosing errors and counterfeit agents with impurities
• If ≥3 missed doses of once-weekly NuSH: consider dose reduction on resumption
• Semaglutide and tirzepatide can be interchanged based on clinical judgment
• Most common adverse effects: GI (nausea, diarrhea, vomiting, abdominal pain, constipation) — mitigated by slow titration

Multidisciplinary Care

• Team-based approach: cardiologist, endocrinologist, dietitian, exercise physiologist, behavioral therapist, pharmacist
• More frequent interactions with weight management team → greater weight loss and maintenance success
• Weight stigma reduction essential; person-first language
• Blood work unlikely to change the decision to pursue NuSH therapies (no labs can detect NuSH contraindications)

Access Considerations

• Annual US costs (2024): semaglutide $14,080; liraglutide $15,738; tirzepatide $8,126
• Significantly lower elsewhere (e.g., liraglutide ~$2,066 in Switzerland)
• Medicare Part D covers NuSH for obesity + T2DM or specific CVD diagnoses; NOT covered for obesity alone
• Compounding sought by patients facing access barriers — carries risk; advocacy ongoing

Limitations of the Document

• No head-to-head RCT comparing NuSH therapies; drug selection recommendations based on indirect comparisons and observational data
• SELECT trial included only patients without T2DM; SURPASS-CVOT (tirzepatide in T2DM+CVD) still ongoing
• SURMOUNT-MMO (tirzepatide in non-T2DM CVD patients) estimated completion 2027 — tirzepatide MACE data outside HFpEF are therefore not yet available
• Longest published NuSH therapy duration is 3.8 years (liraglutide LEADER); obesity is chronic — long-term safety data beyond 5 years are limited
• Compounding and access issues are US-centric; international applicability varies
• Lifestyle intervention benefit is underspecified — additive utility to NuSH evolving in phase 3 data
• The document is a Concise Clinical Guidance, not a full practice guideline; not all recommendations are graded with formal evidence levels

Key Concepts Mentioned

• concepts/NuSH-Therapies — defining framework for liraglutide/semaglutide/tirzepatide drug class
• concepts/GLP-1-Receptor-Agonists — pharmacology, CVOT data, class safety profile
• concepts/Obesity-Paradox — this guidance and SELECT/SUMMIT data further undermine the paradox for intentional pharmacologic weight loss
• concepts/Visceral-Adiposity — central adiposity and CVD risk mechanisms

Key Entities Mentioned

• entities/Obesity — disease definition, epidemiology, CV consequences, weight thresholds
• entities/Semaglutide — GLP-1 RA; SELECT MACE HR 0.80; STEP-HFpEF; SUSTAIN-6
• entities/Tirzepatide — dual GIP/GLP-1 RA; SUMMIT HR 0.62; SURMOUNT-MMO ongoing
• entities/HFpEF — obesity-HFpEF phenotype; semaglutide/tirzepatide benefit
• entities/Heart-Failure — de-escalate diuretics; de-escalate antihypertensives
• entities/MASLD — NuSH therapies improve MASH histology

Wiki Pages Updated

• wiki/sources/weight-mx-acc-2025.md (created)
• wiki/concepts/NuSH-Therapies.md (created)
• wiki/entities/Obesity.md (updated: NuSH pharmacotherapy section, weight thresholds, US prevalence data, source_count 2→3)
• wiki/entities/Semaglutide.md (updated: SELECT trial section, source_count 4→5)
• wiki/entities/Tirzepatide.md (updated: SURMOUNT-MMO, SURPASS-CVOT ongoing, source_count update)
• wiki/concepts/GLP-1-Receptor-Agonists.md (updated: SELECT data, NuSH framework, source_count 4→5)
• wiki/wikiindex.md (updated: NuSH-Therapies concept added; Obesity, Semaglutide, Tirzepatide descriptions updated)
• wiki/sourceindex.md (updated: new source entry)
• log.md (appended)