When treating adults with obesity and adiposity-based chronic disease (ABCD), clinicians should focus on improving overall health and not just reducing body weight, according to a consensus statement from the American Association of Clinical Endocrinology (AACE) published in Endocrine Practice.
An update of the AACE and American College of Endocrinology’s 2016 clinical practice guidelines for the medical care of patients with obesity, the statement primarily focuses on ABCD. According to the AACE, ABCD captures all aspects of excess adiposity, including risk factors that should be addressed for primary prevention, preclinical and clinical obesity, and obesity-related complications and diseases (ORCD).
For the update, the task force created 11 graphic algorithms with accompanying summaries of evidence to facilitate evidence-based, shared decision-making discussions between health care professionals and adults with obesity and ABCD.
“This consensus statement on treatment of those with ABCD centers on the principles of individualized and whole-person health while de-emphasizing weight reduction alone,” the authors said.
Emphasis is placed on optimizing health rather than just weight reduction and achieving clinical goals other than a singular focus on body mass index (ie, complication-centric care).
The statement lays out 9 principles for optimal person-centered management of obesity and ABCD (Algorithm 1), which are then expanded upon in subsequent algorithms. Importantly, the authors wrote, “care should be delivered in an empathetic and culturally sensitive manner, and social determinants of health should be considered in the development of an individualized care plan.”
Screening, Diagnosis, and Staging
Screening and diagnosis (Algorithm 2) should include anthropometric (Algorithm 3) and clinical (Algorithm 4) components, which require both a clinical evaluation and laboratory testing.
The anthropometric component involves confirmation of the presence of excess adiposity and assessment of the distribution of adipose tissue, with ethnicity-specific cutoffs for body mass index (BMI) and adipose distribution. Although BMI can be used for screening, a determination of excess adiposity requires additional inspection and physical examination, including measurements of waist circumference and waist-to-height ratio, which provide insights into cardiometabolic health.
Dual-energy X-ray absorptiometry (DXA), bioelectric impedance, air/water displacement plethysmography, 3-dimensional imaging, and MRI may be used to evaluate body composition and distribution of adipose tissue if there is still uncertainty after initial investigations.
After excess adiposity is confirmed, BMI should be used to classify individuals into the following categories for most parts of the world:
- Overweight (25.0-29.9);
- Class I obesity (30.0-34.9);
- Class II obesity (35.0-39.9); and,
- Class III obesity (≥40.0).
Cutoffs are lower in the Asia-Pacific region because health risks are seen at lower BMIs among these populations. Additionally, BMI may underestimate adiposity among older individuals with frailty and overestimate adiposity among athletes with increased muscle mass.
After screening and anthropometric assessment, clinicians should conduct a comprehensive clinical evaluation for ORCD to stage the severity of disease and determine how adiposity is affecting health and quality of life, which together will determine the appropriate treatment. This process will include taking a medical and weight history, asking about social and family history, and performing a physical examination, an ABCD-focused review of body systems, and basic laboratory testing.
The evaluation should also include consideration of monogenic or syndromic causes of excess adiposity, the possible contribution of medications toward weight gain, endocrinopathies, psychosocial factors, and any other potential contributors.
There are 3 stages of severity:
- Stage 1: No known cardiometabolic, biomechanical, or other obesity-related conditions at present, but there is a risk of future ORCD;
- Stage 2: At least 1 mild to moderate ORCD; and,
- Stage 3: At least 1 severe ORCD.
Stage 1 is analogous to “preclinical” obesity as defined by the Lancet Commission on Obesity, whereas stages 2 and 3 encompass “clinical” obesity.
The AACE staging system takes into account the presence and severity of several ORCD that can be prevented or treated with weight loss, including hypertension, dyslipidemia, dysglycemia, type 2 diabetes, obstructive sleep apnea, atherosclerotic cardiovascular disease (ASCVD), heart failure, atrial fibrillation, chronic kidney disease, and others.
Individualized Treatment Plan, Therapeutic Goals, and Follow-Up
After identifying the severity of disease, clinicians and patients develop a customized, holistic treatment plan (Algorithm 5), using shared decision-making to establish goals of treatment. Throughout follow-up, that plan should be modified as needed on the basis of the clinical response to therapy and goals for longer-term health maintenance. The approach for early weight loss may need to be adjusted to maintain those reductions over time.
Treatment in stage 1 is meant to prevent additional weight gain and stave off the development of ORCD. Treatment in stages 2 and 3 aims to improve health by addressing ORCD.
When developing the treatment plan, which can involve lifestyle intervention, obesity medications, and/or bariatric surgery, clinicians should consider a patient’s access to care, as well as psychological disorders, internalized weight bias, and social determinants of health.
If medications are used for long-term weight loss, the optimal dose that provides the right balance of efficacy and safety may not be the maximally approved dose, the guideline authors noted.
Response to Therapy and Weight Loss Targets
The guideline provides weight-reduction goals that are recommended to mitigate various ORCD (Algorithm 6). For example, weight loss of 5% to 15% is expected to result in clinically meaningful improvements in hyperglycemia, hypertension, dyslipidemia, and polycystic ovary syndrome (PCOS).
The guideline categorizes various degrees of weight loss as follows:
- Incomplete response (≤5%);
- Good response (>5% to <15%); and,
- Excellent response (≥15%).
An excellent response is generally enough to treat or prevent many ORCD, although the impact of various amounts of weight loss will not be the same across all patients.
The guideline authors recommended assessing the early response to obesity medications after about 3 months; if weight loss of at least 5% has not been achieved, then a change in strategy is needed. This change may involve intensification of lifestyle therapy, a new medication, or a combination of drugs. If a patient has lost at least 5% of their body weight, then they should continue with that approach.
The intensity of therapy moving forward should be tailored to the severity or stage of ABCD.
The Role of Behavioral/Lifestyle Therapy
The guideline highlights the importance of using behavioral/lifestyle interventions, in addition to obesity medications and metabolic/bariatric surgery, to improve health outcomes among patients with ABCD (Algorithm 7). Nonpharmacologic approaches include changes to nutrition, physical activity, and sleep, along with efforts to reduce stress.
Nutritional adjustments should go beyond ensuring an energy deficit to focusing on healthy consumption of macro- and micronutrients, which will aid in retaining muscle and bone mass while body weight is reduced. Individuals should get counseling and support to develop personalized nutrition plans and should choose one that they are able to stick with over the long term.
Physical activity should be customized to patient preferences and ability level. It should include increased aerobic activity and resistance/strength training and reduced sedentary behavior. When possible, the amount and intensity of activity should be gradually increased, with a general goal of reaching 150 minutes of moderate-intensity aerobic activity per week, split over at least 3 days per week. Whole-body resistance training sessions are recommended for at least 2 to 3 days per week and should be prioritized to prevent loss of lean muscle mass in the context of weight reduction.
Patients should be screened for sleep disorders and advised to follow good sleep hygiene practices and to optimize sleep quality and duration. If patients are not getting enough sleep, taking steps to extend sleep duration may reduce energy intake and enhance weight loss.
Moreover, patients should be screened for anxiety, depression, stress, eating disorders, and internalized weight bias and offered support to address any issues identified.
Preferred Medications for Complication-Centric Management of ABCD
The guideline contains several sections discussing pharmacological therapy for patients with ABCD, including one that, for the first time, provides preferred medications for specific ORCD on the basis of evidence from phase III clinical trials (Algorithm 8).
The preferred medications for various conditions/scenarios are as follows:
- Prediabetes metabolic syndrome and diabetes prevention: Semaglutide or tirzepatide (preferred), liraglutide or phentermine/topiramate (second tier), and orlistat (third tier);
- Type 2 diabetes: Tirzepatide or semaglutide (first tier), liraglutide and phentermine/topiramate (second tier), and orlistat or naltrexone/bupropion (third tier);
- Major adverse cardiovascular events (MACE) prevention: Semaglutide (only obesity drug that has been shown to reduce these events in a cardiovascular outcome trial);
- Metabolic dysfunction-associated steatohepatitis (MASH): Semaglutide or tirzepatide (preferred);
- Hypertension/blood pressure lowering: Tirzepatide or semaglutide followed by phentermine/topiramate extended release (preferred) and liraglutide or orlistat (second tier);
- Chronic kidney disease: Semaglutide (preferred);
- Heart failure with preserved ejection fraction: Tirzepatide or semaglutide (both have shown benefits);
- Osteoarthritis: Semaglutide (preferred); and,
- Obstructive sleep apnea: Tirzepatide and phentermine/topiramate (preferred).
When choosing therapies, clinicians should consider potential dual benefits, known adverse effects, and costs. In particular, second-generation obesity medications are very expensive, which may limit access to their weight-loss benefits for some patients. Less expensive first-generation medications such as phentermine, orlistat, phentermine/topiramate, naltrexone/bupropion, and liraglutide can be effective for weight loss and treatment of ORCD among many patients.
Step Therapy to Lower Costs and Individualization of Treatment
The guideline provides suggestions for lower-cost pharmacologic step therapy for ABCD (Algorithm 9).
For stages 1 and 2 ABCD, clinicians should consider starting with a first-generation medication that is expected to provide a 5% to 15% weight reduction; for stage 3 disease, clinicians should give strong preference to a second-generation medication that is expected to reduce weight by at least 15%. A good or excellent response to therapy should be sufficient to achieve clinical goals. In the chronic phase, clinicians should consider a cost-effective maintenance plan and taper or discontinue treatment as appropriate.
However, if there is an insufficient response to therapy, a new approach is needed, which might include intensification of lifestyle interventions, a switch in medications, or a combination of drugs.
One suggested approach that may ease costs and improve access for long-term maintenance therapy is to try a first-generation medication for maintenance of weight loss after achieving an initial reduction in body weight with a more expensive second-generation drug.
The document contains a color-coded table to help clinicians individualize drug choices for their patients, with consideration of ORCD type, comorbidities, potential adverse events, and contraindications, as well as the strength of the evidence supporting the therapy (Algorithm 10).
The table is followed by detailed discussions of medications that are approved by the US Food and Drug Administration (FDA) for chronic weight management, including information on patient ages, dosing and titration, observed efficacy, cost, and cautions or contraindications (Algorithm 11).
Clinicians are advised to review FDA labels for additional information on the various medications, which include orlistat, phentermine and other norepinephrine-releasing agents, phentermine and topiramate extended release, naltrexone/bupropion extended release, setmelanotide, cellulose and citric acid hydrogel, liraglutide, semaglutide, and tirzepatide.
The guideline also notes the gastrointestinal side effects of glucagon-like peptide-1 (GLP-1) receptor agonists such as liraglutide, semaglutide, and tirzepatide (a dual agonist of the GLP-1 and glucose-dependent insulinotropic polypeptide receptors), which mostly occur during dose escalation. Clinicians should start at the lowest dose and slowing titrate to help ease potential side effects.
The authors advised against using compounded alternatives to FDA-approved semaglutide and tirzepatide, which are often dispensed by online pharmacies and have not had their safety, efficacy, or quality verified.
“This 2025 algorithm for the medical care of adults with obesity underscores that ABCD is a complex, chronic disease that necessitates long-term treatment and care. Emphasis is placed on optimizing health rather than just weight reduction and achieving clinical goals other than a singular focus on body mass index (ie, complication-centric care),” the guideline authors concluded.
References:
Nadolsky K, Garvey WT, Agarwal M, et al. American Association of Clinical Endocrinology consensus statement: algorithm for the evaluation and treatment of adults with obesity/adiposity-based chronic disease – 2025 update. Endocr Pract. Published online September 16, 2025. doi:10.1016/j.eprac.2025.07.017
