Do not select therapy on expected weight reduction alone. Identify the complication or clinical outcome most important to improve: established cardiovascular disease moderate-to-severe obstructive sleep apnea noncirrhotic MASH with F2–F3 fibrosis type 2 diabetes / glycemic-metabolic priority other obesity-related complications weight reduction when no single complication predominates Multiple goals may coexist; prioritize according to clinical risk, evidence, patient preference and treatment feasibility.
-
Established Cardiovascular Disease
Semaglutide (Wegovy) — specifically indicated to reduce CV death, nonfatal MI and nonfatal stroke. Dosing: 0.25 mg SC weekly ×4 wk → 0.5 ×4 → 1.0 ×4 → 1.7 ×4 → 2.4 mg weekly. Recommended maintenance 2.4 mg; 1.7 mg can be used based on response/tolerability. Look out for GI intolerance, dehydration/AKI, gallbladder disease, pancreatitis, increased HR; hypoglycemia if insulin/SU; diabetic retinopathy in T2D. Monitor weight, BP and CV status.
-
Select GLP-1–based therapy using complication-specific evidence
When a complication-specific FDA indication or high-quality outcomes evidence applies, incorporate that evidence directly into treatment selection. Otherwise, select treatment according to overall efficacy, safety, comorbidities, tolerability, route, access and patient preference. Avoid assuming that greater weight loss alone identifies the clinically optimal therapy for every patient.
-
Semaglutide strategy
Current U.S. indications for Wegovy include: chronic weight reduction and long-term weight maintenance; reduction of major adverse cardiovascular events in adults with established cardiovascular disease and overweight or obesity; and treatment of noncirrhotic MASH with F2–F3 fibrosis in adults. Match formulation and dose to the specific indication. Current U.S. labeling also includes oral Wegovy tablets for cardiovascular risk reduction and adult weight reduction; the MASH indication applies to Wegovy injection.
-
Titrate according to indication and tolerability
Semaglutide injection Start 0.25 mg once weekly and escalate every 4 weeks: 0.25 → 0.5 → 1.0 → 1.7 mg → indication-specific maintenance dose. - CV risk reduction: 2.4 mg recommended; 1.7 mg may be used according to response/tolerability. - Adult weight reduction: 2.4 mg recommended; 1.7 mg may be used according to response/tolerability. - MASH F2–F3: 2.4 mg weekly; if not tolerated, reduce to 1.7 mg and consider subsequent re-escalation. Tirzepatide Start 2.5 mg once weekly for 4 weeks, then increase to 5 mg. Further increases may be made in 2.5-mg increments after ≥4 weeks at the current dose. - Weight management: maintenance 5, 10 or 15 mg weekly. - OSA: maintenance 10 or 15 mg weekly. Delay dose escalation when needed for tolerability.
-
Monitor benefit beyond body weight
Reassess both weight-related and complication-specific outcomes. Monitor: body-weight trajectory and maintenance waist circumference and waist-to-height ratio glycemia and cardiometabolic risk factors target complication outcomes physical function and mobility quality of life treatment tolerability and adverse effects adherence and treatment burden Use complication-specific measures when relevant, such as OSA symptoms/AHI, glycemic measures or liver assessment.
-
Is therapy providing clinically meaningful benefit?
Assess treatment response against the individualized goals established before therapy. Consider: magnitude and durability of weight reduction improvement in the target complication metabolic and cardiovascular health function and quality of life tolerability patient priorities Meaningful benefit + acceptable tolerability → continue. Insufficient benefit or unacceptable treatment burden → reassess strategy.
-
Continue and individualize long-term therapy
Continue treatment when clinically meaningful benefit is sustained and treatment remains acceptable to the patient. Obesity/adiposity-based chronic disease generally requires long-term management. Continue lifestyle therapy and periodically reassess weight, complications, function, treatment burden and patient goals.
-
Reassess strategy if benefit or tolerability is inadequate
Reassess: adherence and treatment access dose and titration adverse effects weight-promoting medications untreated contributors or complications original treatment goal Consider slower titration, dose adjustment, switching therapy, use of another evidence-based anti-obesity medication, combination strategies when appropriate, or specialist referral.
-
Consider metabolic/bariatric surgery when appropriate
Consider referral for metabolic/bariatric surgery according to current eligibility criteria, local guidance and patient preference. Current ASMBS/IFSO guidance recommends metabolic/bariatric surgery for BMI ≥35 kg/m² regardless of the presence or severity of obesity-related comorbidities. Surgery should also be considered in selected adults with BMI 30–34.9 kg/m² and metabolic disease, or when durable weight loss or improvement in obesity-related disease is not achieved with nonsurgical treatment.
-
Tirzepatide strategy
Current U.S. indications for Zepbound include: chronic weight reduction and long-term weight maintenance in eligible adults; and treatment of moderate-to-severe obstructive sleep apnea in adults with obesity. Select the maintenance dose according to the indication, clinical response and tolerability.
-
Titrate according to indication and tolerability
Semaglutide injection Start 0.25 mg once weekly and escalate every 4 weeks: 0.25 → 0.5 → 1.0 → 1.7 mg → indication-specific maintenance dose. - CV risk reduction: 2.4 mg recommended; 1.7 mg may be used according to response/tolerability. - Adult weight reduction: 2.4 mg recommended; 1.7 mg may be used according to response/tolerability. - MASH F2–F3: 2.4 mg weekly; if not tolerated, reduce to 1.7 mg and consider subsequent re-escalation. Tirzepatide Start 2.5 mg once weekly for 4 weeks, then increase to 5 mg. Further increases may be made in 2.5-mg increments after ≥4 weeks at the current dose. - Weight management: maintenance 5, 10 or 15 mg weekly. - OSA: maintenance 10 or 15 mg weekly. Delay dose escalation when needed for tolerability.
-
Monitor benefit beyond body weight
Reassess both weight-related and complication-specific outcomes. Monitor: body-weight trajectory and maintenance waist circumference and waist-to-height ratio glycemia and cardiometabolic risk factors target complication outcomes physical function and mobility quality of life treatment tolerability and adverse effects adherence and treatment burden Use complication-specific measures when relevant, such as OSA symptoms/AHI, glycemic measures or liver assessment.
-
Is therapy providing clinically meaningful benefit?
Assess treatment response against the individualized goals established before therapy. Consider: magnitude and durability of weight reduction improvement in the target complication metabolic and cardiovascular health function and quality of life tolerability patient priorities Meaningful benefit + acceptable tolerability → continue. Insufficient benefit or unacceptable treatment burden → reassess strategy.
-
Continue and individualize long-term therapy
Continue treatment when clinically meaningful benefit is sustained and treatment remains acceptable to the patient. Obesity/adiposity-based chronic disease generally requires long-term management. Continue lifestyle therapy and periodically reassess weight, complications, function, treatment burden and patient goals.
-
Reassess strategy if benefit or tolerability is inadequate
Reassess: adherence and treatment access dose and titration adverse effects weight-promoting medications untreated contributors or complications original treatment goal Consider slower titration, dose adjustment, switching therapy, use of another evidence-based anti-obesity medication, combination strategies when appropriate, or specialist referral.
-
Consider metabolic/bariatric surgery when appropriate
Consider referral for metabolic/bariatric surgery according to current eligibility criteria, local guidance and patient preference. Current ASMBS/IFSO guidance recommends metabolic/bariatric surgery for BMI ≥35 kg/m² regardless of the presence or severity of obesity-related comorbidities. Surgery should also be considered in selected adults with BMI 30–34.9 kg/m² and metabolic disease, or when durable weight loss or improvement in obesity-related disease is not achieved with nonsurgical treatment.
-
Moderate-to-severe obstructive sleep apnea (OSA) with obesity
Tirzepatide (Zepbound) — specifically FDA-approved for this population Dosing: 2.5 mg SC weekly ×4 wk → 5 mg; increase by 2.5 mg after ≥4 wk at each dose → 10 or 15 mg weekly maintenance. Look out for GI intolerance, dehydration/renal function, gallbladder disease, pancreatitis. Follow AHI, daytime symptoms, oxygenation and PAP use; don’t prematurely stop established PAP solely because weight is falling.
-
Select GLP-1–based therapy using complication-specific evidence
When a complication-specific FDA indication or high-quality outcomes evidence applies, incorporate that evidence directly into treatment selection. Otherwise, select treatment according to overall efficacy, safety, comorbidities, tolerability, route, access and patient preference. Avoid assuming that greater weight loss alone identifies the clinically optimal therapy for every patient.
-
Semaglutide strategy
Current U.S. indications for Wegovy include: chronic weight reduction and long-term weight maintenance; reduction of major adverse cardiovascular events in adults with established cardiovascular disease and overweight or obesity; and treatment of noncirrhotic MASH with F2–F3 fibrosis in adults. Match formulation and dose to the specific indication. Current U.S. labeling also includes oral Wegovy tablets for cardiovascular risk reduction and adult weight reduction; the MASH indication applies to Wegovy injection.
-
Titrate according to indication and tolerability
Semaglutide injection Start 0.25 mg once weekly and escalate every 4 weeks: 0.25 → 0.5 → 1.0 → 1.7 mg → indication-specific maintenance dose. - CV risk reduction: 2.4 mg recommended; 1.7 mg may be used according to response/tolerability. - Adult weight reduction: 2.4 mg recommended; 1.7 mg may be used according to response/tolerability. - MASH F2–F3: 2.4 mg weekly; if not tolerated, reduce to 1.7 mg and consider subsequent re-escalation. Tirzepatide Start 2.5 mg once weekly for 4 weeks, then increase to 5 mg. Further increases may be made in 2.5-mg increments after ≥4 weeks at the current dose. - Weight management: maintenance 5, 10 or 15 mg weekly. - OSA: maintenance 10 or 15 mg weekly. Delay dose escalation when needed for tolerability.
-
Monitor benefit beyond body weight
Reassess both weight-related and complication-specific outcomes. Monitor: body-weight trajectory and maintenance waist circumference and waist-to-height ratio glycemia and cardiometabolic risk factors target complication outcomes physical function and mobility quality of life treatment tolerability and adverse effects adherence and treatment burden Use complication-specific measures when relevant, such as OSA symptoms/AHI, glycemic measures or liver assessment.
-
Is therapy providing clinically meaningful benefit?
Assess treatment response against the individualized goals established before therapy. Consider: magnitude and durability of weight reduction improvement in the target complication metabolic and cardiovascular health function and quality of life tolerability patient priorities Meaningful benefit + acceptable tolerability → continue. Insufficient benefit or unacceptable treatment burden → reassess strategy.
-
Continue and individualize long-term therapy
Continue treatment when clinically meaningful benefit is sustained and treatment remains acceptable to the patient. Obesity/adiposity-based chronic disease generally requires long-term management. Continue lifestyle therapy and periodically reassess weight, complications, function, treatment burden and patient goals.
-
Reassess strategy if benefit or tolerability is inadequate
Reassess: adherence and treatment access dose and titration adverse effects weight-promoting medications untreated contributors or complications original treatment goal Consider slower titration, dose adjustment, switching therapy, use of another evidence-based anti-obesity medication, combination strategies when appropriate, or specialist referral.
-
Consider metabolic/bariatric surgery when appropriate
Consider referral for metabolic/bariatric surgery according to current eligibility criteria, local guidance and patient preference. Current ASMBS/IFSO guidance recommends metabolic/bariatric surgery for BMI ≥35 kg/m² regardless of the presence or severity of obesity-related comorbidities. Surgery should also be considered in selected adults with BMI 30–34.9 kg/m² and metabolic disease, or when durable weight loss or improvement in obesity-related disease is not achieved with nonsurgical treatment.
-
Tirzepatide strategy
Current U.S. indications for Zepbound include: chronic weight reduction and long-term weight maintenance in eligible adults; and treatment of moderate-to-severe obstructive sleep apnea in adults with obesity. Select the maintenance dose according to the indication, clinical response and tolerability.
-
Titrate according to indication and tolerability
Semaglutide injection Start 0.25 mg once weekly and escalate every 4 weeks: 0.25 → 0.5 → 1.0 → 1.7 mg → indication-specific maintenance dose. - CV risk reduction: 2.4 mg recommended; 1.7 mg may be used according to response/tolerability. - Adult weight reduction: 2.4 mg recommended; 1.7 mg may be used according to response/tolerability. - MASH F2–F3: 2.4 mg weekly; if not tolerated, reduce to 1.7 mg and consider subsequent re-escalation. Tirzepatide Start 2.5 mg once weekly for 4 weeks, then increase to 5 mg. Further increases may be made in 2.5-mg increments after ≥4 weeks at the current dose. - Weight management: maintenance 5, 10 or 15 mg weekly. - OSA: maintenance 10 or 15 mg weekly. Delay dose escalation when needed for tolerability.
-
Monitor benefit beyond body weight
Reassess both weight-related and complication-specific outcomes. Monitor: body-weight trajectory and maintenance waist circumference and waist-to-height ratio glycemia and cardiometabolic risk factors target complication outcomes physical function and mobility quality of life treatment tolerability and adverse effects adherence and treatment burden Use complication-specific measures when relevant, such as OSA symptoms/AHI, glycemic measures or liver assessment.
-
Is therapy providing clinically meaningful benefit?
Assess treatment response against the individualized goals established before therapy. Consider: magnitude and durability of weight reduction improvement in the target complication metabolic and cardiovascular health function and quality of life tolerability patient priorities Meaningful benefit + acceptable tolerability → continue. Insufficient benefit or unacceptable treatment burden → reassess strategy.
-
Continue and individualize long-term therapy
Continue treatment when clinically meaningful benefit is sustained and treatment remains acceptable to the patient. Obesity/adiposity-based chronic disease generally requires long-term management. Continue lifestyle therapy and periodically reassess weight, complications, function, treatment burden and patient goals.
-
Reassess strategy if benefit or tolerability is inadequate
Reassess: adherence and treatment access dose and titration adverse effects weight-promoting medications untreated contributors or complications original treatment goal Consider slower titration, dose adjustment, switching therapy, use of another evidence-based anti-obesity medication, combination strategies when appropriate, or specialist referral.
-
Consider metabolic/bariatric surgery when appropriate
Consider referral for metabolic/bariatric surgery according to current eligibility criteria, local guidance and patient preference. Current ASMBS/IFSO guidance recommends metabolic/bariatric surgery for BMI ≥35 kg/m² regardless of the presence or severity of obesity-related comorbidities. Surgery should also be considered in selected adults with BMI 30–34.9 kg/m² and metabolic disease, or when durable weight loss or improvement in obesity-related disease is not achieved with nonsurgical treatment.
-
Noncirrhotic MASH with F2–F3 fibrosis
Semaglutide injection (Wegovy) — FDA-approved for this specific population Dosing: Same escalation to 2.4 mg SC weekly. If 2.4 mg isn’t tolerated, reduce to 1.7 mg and consider re-escalation. Confirm noncirrhotic F2–F3 disease. Follow liver tests/fibrosis assessment and metabolic risk; watch for hepatic decompensation. Also standard GLP-1 GI, gallbladder and pancreatitis precautions.
-
Select GLP-1–based therapy using complication-specific evidence
When a complication-specific FDA indication or high-quality outcomes evidence applies, incorporate that evidence directly into treatment selection. Otherwise, select treatment according to overall efficacy, safety, comorbidities, tolerability, route, access and patient preference. Avoid assuming that greater weight loss alone identifies the clinically optimal therapy for every patient.
-
Semaglutide strategy
Current U.S. indications for Wegovy include: chronic weight reduction and long-term weight maintenance; reduction of major adverse cardiovascular events in adults with established cardiovascular disease and overweight or obesity; and treatment of noncirrhotic MASH with F2–F3 fibrosis in adults. Match formulation and dose to the specific indication. Current U.S. labeling also includes oral Wegovy tablets for cardiovascular risk reduction and adult weight reduction; the MASH indication applies to Wegovy injection.
-
Titrate according to indication and tolerability
Semaglutide injection Start 0.25 mg once weekly and escalate every 4 weeks: 0.25 → 0.5 → 1.0 → 1.7 mg → indication-specific maintenance dose. - CV risk reduction: 2.4 mg recommended; 1.7 mg may be used according to response/tolerability. - Adult weight reduction: 2.4 mg recommended; 1.7 mg may be used according to response/tolerability. - MASH F2–F3: 2.4 mg weekly; if not tolerated, reduce to 1.7 mg and consider subsequent re-escalation. Tirzepatide Start 2.5 mg once weekly for 4 weeks, then increase to 5 mg. Further increases may be made in 2.5-mg increments after ≥4 weeks at the current dose. - Weight management: maintenance 5, 10 or 15 mg weekly. - OSA: maintenance 10 or 15 mg weekly. Delay dose escalation when needed for tolerability.
-
Monitor benefit beyond body weight
Reassess both weight-related and complication-specific outcomes. Monitor: body-weight trajectory and maintenance waist circumference and waist-to-height ratio glycemia and cardiometabolic risk factors target complication outcomes physical function and mobility quality of life treatment tolerability and adverse effects adherence and treatment burden Use complication-specific measures when relevant, such as OSA symptoms/AHI, glycemic measures or liver assessment.
-
Is therapy providing clinically meaningful benefit?
Assess treatment response against the individualized goals established before therapy. Consider: magnitude and durability of weight reduction improvement in the target complication metabolic and cardiovascular health function and quality of life tolerability patient priorities Meaningful benefit + acceptable tolerability → continue. Insufficient benefit or unacceptable treatment burden → reassess strategy.
-
Continue and individualize long-term therapy
Continue treatment when clinically meaningful benefit is sustained and treatment remains acceptable to the patient. Obesity/adiposity-based chronic disease generally requires long-term management. Continue lifestyle therapy and periodically reassess weight, complications, function, treatment burden and patient goals.
-
Reassess strategy if benefit or tolerability is inadequate
Reassess: adherence and treatment access dose and titration adverse effects weight-promoting medications untreated contributors or complications original treatment goal Consider slower titration, dose adjustment, switching therapy, use of another evidence-based anti-obesity medication, combination strategies when appropriate, or specialist referral.
-
Consider metabolic/bariatric surgery when appropriate
Consider referral for metabolic/bariatric surgery according to current eligibility criteria, local guidance and patient preference. Current ASMBS/IFSO guidance recommends metabolic/bariatric surgery for BMI ≥35 kg/m² regardless of the presence or severity of obesity-related comorbidities. Surgery should also be considered in selected adults with BMI 30–34.9 kg/m² and metabolic disease, or when durable weight loss or improvement in obesity-related disease is not achieved with nonsurgical treatment.
-
Tirzepatide strategy
Current U.S. indications for Zepbound include: chronic weight reduction and long-term weight maintenance in eligible adults; and treatment of moderate-to-severe obstructive sleep apnea in adults with obesity. Select the maintenance dose according to the indication, clinical response and tolerability.
-
Titrate according to indication and tolerability
Semaglutide injection Start 0.25 mg once weekly and escalate every 4 weeks: 0.25 → 0.5 → 1.0 → 1.7 mg → indication-specific maintenance dose. - CV risk reduction: 2.4 mg recommended; 1.7 mg may be used according to response/tolerability. - Adult weight reduction: 2.4 mg recommended; 1.7 mg may be used according to response/tolerability. - MASH F2–F3: 2.4 mg weekly; if not tolerated, reduce to 1.7 mg and consider subsequent re-escalation. Tirzepatide Start 2.5 mg once weekly for 4 weeks, then increase to 5 mg. Further increases may be made in 2.5-mg increments after ≥4 weeks at the current dose. - Weight management: maintenance 5, 10 or 15 mg weekly. - OSA: maintenance 10 or 15 mg weekly. Delay dose escalation when needed for tolerability.
-
Monitor benefit beyond body weight
Reassess both weight-related and complication-specific outcomes. Monitor: body-weight trajectory and maintenance waist circumference and waist-to-height ratio glycemia and cardiometabolic risk factors target complication outcomes physical function and mobility quality of life treatment tolerability and adverse effects adherence and treatment burden Use complication-specific measures when relevant, such as OSA symptoms/AHI, glycemic measures or liver assessment.
-
Is therapy providing clinically meaningful benefit?
Assess treatment response against the individualized goals established before therapy. Consider: magnitude and durability of weight reduction improvement in the target complication metabolic and cardiovascular health function and quality of life tolerability patient priorities Meaningful benefit + acceptable tolerability → continue. Insufficient benefit or unacceptable treatment burden → reassess strategy.
-
Continue and individualize long-term therapy
Continue treatment when clinically meaningful benefit is sustained and treatment remains acceptable to the patient. Obesity/adiposity-based chronic disease generally requires long-term management. Continue lifestyle therapy and periodically reassess weight, complications, function, treatment burden and patient goals.
-
Reassess strategy if benefit or tolerability is inadequate
Reassess: adherence and treatment access dose and titration adverse effects weight-promoting medications untreated contributors or complications original treatment goal Consider slower titration, dose adjustment, switching therapy, use of another evidence-based anti-obesity medication, combination strategies when appropriate, or specialist referral.
-
Consider metabolic/bariatric surgery when appropriate
Consider referral for metabolic/bariatric surgery according to current eligibility criteria, local guidance and patient preference. Current ASMBS/IFSO guidance recommends metabolic/bariatric surgery for BMI ≥35 kg/m² regardless of the presence or severity of obesity-related comorbidities. Surgery should also be considered in selected adults with BMI 30–34.9 kg/m² and metabolic disease, or when durable weight loss or improvement in obesity-related disease is not achieved with nonsurgical treatment.
-
Type 2 diabetes or glycemic-metabolic priority
Semaglutide or tirzepatide, individualized with the overall diabetes/CV/renal regimen. The current algorithm deliberately does not designate one universally preferred agent. For obesity: semaglutide → 2.4 mg weekly; tirzepatide → 5, 10 or 15 mg weekly maintenance. Look out for HbA1c/glucose and hypoglycemia, particularly with insulin or sulfonylureas—dose reduction may be needed. With semaglutide, monitor patients with pre-existing diabetic retinopathy, especially with rapid glucose improvement. Consider CKD/CVD when choosing the complete diabetes regimen.
-
Select GLP-1–based therapy using complication-specific evidence
When a complication-specific FDA indication or high-quality outcomes evidence applies, incorporate that evidence directly into treatment selection. Otherwise, select treatment according to overall efficacy, safety, comorbidities, tolerability, route, access and patient preference. Avoid assuming that greater weight loss alone identifies the clinically optimal therapy for every patient.
-
Semaglutide strategy
Current U.S. indications for Wegovy include: chronic weight reduction and long-term weight maintenance; reduction of major adverse cardiovascular events in adults with established cardiovascular disease and overweight or obesity; and treatment of noncirrhotic MASH with F2–F3 fibrosis in adults. Match formulation and dose to the specific indication. Current U.S. labeling also includes oral Wegovy tablets for cardiovascular risk reduction and adult weight reduction; the MASH indication applies to Wegovy injection.
-
Titrate according to indication and tolerability
Semaglutide injection Start 0.25 mg once weekly and escalate every 4 weeks: 0.25 → 0.5 → 1.0 → 1.7 mg → indication-specific maintenance dose. - CV risk reduction: 2.4 mg recommended; 1.7 mg may be used according to response/tolerability. - Adult weight reduction: 2.4 mg recommended; 1.7 mg may be used according to response/tolerability. - MASH F2–F3: 2.4 mg weekly; if not tolerated, reduce to 1.7 mg and consider subsequent re-escalation. Tirzepatide Start 2.5 mg once weekly for 4 weeks, then increase to 5 mg. Further increases may be made in 2.5-mg increments after ≥4 weeks at the current dose. - Weight management: maintenance 5, 10 or 15 mg weekly. - OSA: maintenance 10 or 15 mg weekly. Delay dose escalation when needed for tolerability.
-
Monitor benefit beyond body weight
Reassess both weight-related and complication-specific outcomes. Monitor: body-weight trajectory and maintenance waist circumference and waist-to-height ratio glycemia and cardiometabolic risk factors target complication outcomes physical function and mobility quality of life treatment tolerability and adverse effects adherence and treatment burden Use complication-specific measures when relevant, such as OSA symptoms/AHI, glycemic measures or liver assessment.
-
Is therapy providing clinically meaningful benefit?
Assess treatment response against the individualized goals established before therapy. Consider: magnitude and durability of weight reduction improvement in the target complication metabolic and cardiovascular health function and quality of life tolerability patient priorities Meaningful benefit + acceptable tolerability → continue. Insufficient benefit or unacceptable treatment burden → reassess strategy.
-
Continue and individualize long-term therapy
Continue treatment when clinically meaningful benefit is sustained and treatment remains acceptable to the patient. Obesity/adiposity-based chronic disease generally requires long-term management. Continue lifestyle therapy and periodically reassess weight, complications, function, treatment burden and patient goals.
-
Reassess strategy if benefit or tolerability is inadequate
Reassess: adherence and treatment access dose and titration adverse effects weight-promoting medications untreated contributors or complications original treatment goal Consider slower titration, dose adjustment, switching therapy, use of another evidence-based anti-obesity medication, combination strategies when appropriate, or specialist referral.
-
Consider metabolic/bariatric surgery when appropriate
Consider referral for metabolic/bariatric surgery according to current eligibility criteria, local guidance and patient preference. Current ASMBS/IFSO guidance recommends metabolic/bariatric surgery for BMI ≥35 kg/m² regardless of the presence or severity of obesity-related comorbidities. Surgery should also be considered in selected adults with BMI 30–34.9 kg/m² and metabolic disease, or when durable weight loss or improvement in obesity-related disease is not achieved with nonsurgical treatment.
-
Tirzepatide strategy
Current U.S. indications for Zepbound include: chronic weight reduction and long-term weight maintenance in eligible adults; and treatment of moderate-to-severe obstructive sleep apnea in adults with obesity. Select the maintenance dose according to the indication, clinical response and tolerability.
-
Titrate according to indication and tolerability
Semaglutide injection Start 0.25 mg once weekly and escalate every 4 weeks: 0.25 → 0.5 → 1.0 → 1.7 mg → indication-specific maintenance dose. - CV risk reduction: 2.4 mg recommended; 1.7 mg may be used according to response/tolerability. - Adult weight reduction: 2.4 mg recommended; 1.7 mg may be used according to response/tolerability. - MASH F2–F3: 2.4 mg weekly; if not tolerated, reduce to 1.7 mg and consider subsequent re-escalation. Tirzepatide Start 2.5 mg once weekly for 4 weeks, then increase to 5 mg. Further increases may be made in 2.5-mg increments after ≥4 weeks at the current dose. - Weight management: maintenance 5, 10 or 15 mg weekly. - OSA: maintenance 10 or 15 mg weekly. Delay dose escalation when needed for tolerability.
-
Monitor benefit beyond body weight
Reassess both weight-related and complication-specific outcomes. Monitor: body-weight trajectory and maintenance waist circumference and waist-to-height ratio glycemia and cardiometabolic risk factors target complication outcomes physical function and mobility quality of life treatment tolerability and adverse effects adherence and treatment burden Use complication-specific measures when relevant, such as OSA symptoms/AHI, glycemic measures or liver assessment.
-
Is therapy providing clinically meaningful benefit?
Assess treatment response against the individualized goals established before therapy. Consider: magnitude and durability of weight reduction improvement in the target complication metabolic and cardiovascular health function and quality of life tolerability patient priorities Meaningful benefit + acceptable tolerability → continue. Insufficient benefit or unacceptable treatment burden → reassess strategy.
-
Continue and individualize long-term therapy
Continue treatment when clinically meaningful benefit is sustained and treatment remains acceptable to the patient. Obesity/adiposity-based chronic disease generally requires long-term management. Continue lifestyle therapy and periodically reassess weight, complications, function, treatment burden and patient goals.
-
Reassess strategy if benefit or tolerability is inadequate
Reassess: adherence and treatment access dose and titration adverse effects weight-promoting medications untreated contributors or complications original treatment goal Consider slower titration, dose adjustment, switching therapy, use of another evidence-based anti-obesity medication, combination strategies when appropriate, or specialist referral.
-
Consider metabolic/bariatric surgery when appropriate
Consider referral for metabolic/bariatric surgery according to current eligibility criteria, local guidance and patient preference. Current ASMBS/IFSO guidance recommends metabolic/bariatric surgery for BMI ≥35 kg/m² regardless of the presence or severity of obesity-related comorbidities. Surgery should also be considered in selected adults with BMI 30–34.9 kg/m² and metabolic disease, or when durable weight loss or improvement in obesity-related disease is not achieved with nonsurgical treatment.
-
Other obesity-related complications
Such as HTN, dyslipidemia, CKD, OA/mobility limitation. Semaglutide or tirzepatide based on the specific complication, evidence, desired weight loss, safety and patient factors. These are not all complication-specific FDA indications. Standard obesity dosing: semaglutide → 1.7 or 2.4 mg weekly; tirzepatide → 5, 10 or 15 mg weekly after titration. Measure the actual complication, not just weight: BP/antihypertensive need, lipids, renal function/albuminuria, pain/function/mobility, etc. Avoid implying that every obesity complication has a drug-specific labeled indication.
-
Select GLP-1–based therapy using complication-specific evidence
When a complication-specific FDA indication or high-quality outcomes evidence applies, incorporate that evidence directly into treatment selection. Otherwise, select treatment according to overall efficacy, safety, comorbidities, tolerability, route, access and patient preference. Avoid assuming that greater weight loss alone identifies the clinically optimal therapy for every patient.
-
Semaglutide strategy
Current U.S. indications for Wegovy include: chronic weight reduction and long-term weight maintenance; reduction of major adverse cardiovascular events in adults with established cardiovascular disease and overweight or obesity; and treatment of noncirrhotic MASH with F2–F3 fibrosis in adults. Match formulation and dose to the specific indication. Current U.S. labeling also includes oral Wegovy tablets for cardiovascular risk reduction and adult weight reduction; the MASH indication applies to Wegovy injection.
-
Titrate according to indication and tolerability
Semaglutide injection Start 0.25 mg once weekly and escalate every 4 weeks: 0.25 → 0.5 → 1.0 → 1.7 mg → indication-specific maintenance dose. - CV risk reduction: 2.4 mg recommended; 1.7 mg may be used according to response/tolerability. - Adult weight reduction: 2.4 mg recommended; 1.7 mg may be used according to response/tolerability. - MASH F2–F3: 2.4 mg weekly; if not tolerated, reduce to 1.7 mg and consider subsequent re-escalation. Tirzepatide Start 2.5 mg once weekly for 4 weeks, then increase to 5 mg. Further increases may be made in 2.5-mg increments after ≥4 weeks at the current dose. - Weight management: maintenance 5, 10 or 15 mg weekly. - OSA: maintenance 10 or 15 mg weekly. Delay dose escalation when needed for tolerability.
-
Monitor benefit beyond body weight
Reassess both weight-related and complication-specific outcomes. Monitor: body-weight trajectory and maintenance waist circumference and waist-to-height ratio glycemia and cardiometabolic risk factors target complication outcomes physical function and mobility quality of life treatment tolerability and adverse effects adherence and treatment burden Use complication-specific measures when relevant, such as OSA symptoms/AHI, glycemic measures or liver assessment.
-
Is therapy providing clinically meaningful benefit?
Assess treatment response against the individualized goals established before therapy. Consider: magnitude and durability of weight reduction improvement in the target complication metabolic and cardiovascular health function and quality of life tolerability patient priorities Meaningful benefit + acceptable tolerability → continue. Insufficient benefit or unacceptable treatment burden → reassess strategy.
-
Continue and individualize long-term therapy
Continue treatment when clinically meaningful benefit is sustained and treatment remains acceptable to the patient. Obesity/adiposity-based chronic disease generally requires long-term management. Continue lifestyle therapy and periodically reassess weight, complications, function, treatment burden and patient goals.
-
Reassess strategy if benefit or tolerability is inadequate
Reassess: adherence and treatment access dose and titration adverse effects weight-promoting medications untreated contributors or complications original treatment goal Consider slower titration, dose adjustment, switching therapy, use of another evidence-based anti-obesity medication, combination strategies when appropriate, or specialist referral.
-
Consider metabolic/bariatric surgery when appropriate
Consider referral for metabolic/bariatric surgery according to current eligibility criteria, local guidance and patient preference. Current ASMBS/IFSO guidance recommends metabolic/bariatric surgery for BMI ≥35 kg/m² regardless of the presence or severity of obesity-related comorbidities. Surgery should also be considered in selected adults with BMI 30–34.9 kg/m² and metabolic disease, or when durable weight loss or improvement in obesity-related disease is not achieved with nonsurgical treatment.
-
Tirzepatide strategy
Current U.S. indications for Zepbound include: chronic weight reduction and long-term weight maintenance in eligible adults; and treatment of moderate-to-severe obstructive sleep apnea in adults with obesity. Select the maintenance dose according to the indication, clinical response and tolerability.
-
Titrate according to indication and tolerability
Semaglutide injection Start 0.25 mg once weekly and escalate every 4 weeks: 0.25 → 0.5 → 1.0 → 1.7 mg → indication-specific maintenance dose. - CV risk reduction: 2.4 mg recommended; 1.7 mg may be used according to response/tolerability. - Adult weight reduction: 2.4 mg recommended; 1.7 mg may be used according to response/tolerability. - MASH F2–F3: 2.4 mg weekly; if not tolerated, reduce to 1.7 mg and consider subsequent re-escalation. Tirzepatide Start 2.5 mg once weekly for 4 weeks, then increase to 5 mg. Further increases may be made in 2.5-mg increments after ≥4 weeks at the current dose. - Weight management: maintenance 5, 10 or 15 mg weekly. - OSA: maintenance 10 or 15 mg weekly. Delay dose escalation when needed for tolerability.
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Monitor benefit beyond body weight
Reassess both weight-related and complication-specific outcomes. Monitor: body-weight trajectory and maintenance waist circumference and waist-to-height ratio glycemia and cardiometabolic risk factors target complication outcomes physical function and mobility quality of life treatment tolerability and adverse effects adherence and treatment burden Use complication-specific measures when relevant, such as OSA symptoms/AHI, glycemic measures or liver assessment.
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Is therapy providing clinically meaningful benefit?
Assess treatment response against the individualized goals established before therapy. Consider: magnitude and durability of weight reduction improvement in the target complication metabolic and cardiovascular health function and quality of life tolerability patient priorities Meaningful benefit + acceptable tolerability → continue. Insufficient benefit or unacceptable treatment burden → reassess strategy.
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Continue and individualize long-term therapy
Continue treatment when clinically meaningful benefit is sustained and treatment remains acceptable to the patient. Obesity/adiposity-based chronic disease generally requires long-term management. Continue lifestyle therapy and periodically reassess weight, complications, function, treatment burden and patient goals.
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Reassess strategy if benefit or tolerability is inadequate
Reassess: adherence and treatment access dose and titration adverse effects weight-promoting medications untreated contributors or complications original treatment goal Consider slower titration, dose adjustment, switching therapy, use of another evidence-based anti-obesity medication, combination strategies when appropriate, or specialist referral.
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Consider metabolic/bariatric surgery when appropriate
Consider referral for metabolic/bariatric surgery according to current eligibility criteria, local guidance and patient preference. Current ASMBS/IFSO guidance recommends metabolic/bariatric surgery for BMI ≥35 kg/m² regardless of the presence or severity of obesity-related comorbidities. Surgery should also be considered in selected adults with BMI 30–34.9 kg/m² and metabolic disease, or when durable weight loss or improvement in obesity-related disease is not achieved with nonsurgical treatment.
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No predominant obesity-related complication
Semaglutide or tirzepatide; select according to desired efficacy, tolerability, contraindications, preference, access and cost. Semaglutide: 0.25 → 0.5 → 1.0 → 1.7 → 2.4 mg weekly every 4 wk. Tirzepatide: 2.5 → 5 → 7.5 → 10 → 12.5 → 15 mg max weekly, ≥4 wk between increases; maintenance 5, 10 or 15 mg. Look out for weight/waist trajectory, GI tolerability, hydration, renal function when indicated, gallbladder symptoms, pancreatitis symptoms, nutritional intake and preservation of lean mass/function. Slow or delay escalation when intolerance occurs.
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Select GLP-1–based therapy using complication-specific evidence
When a complication-specific FDA indication or high-quality outcomes evidence applies, incorporate that evidence directly into treatment selection. Otherwise, select treatment according to overall efficacy, safety, comorbidities, tolerability, route, access and patient preference. Avoid assuming that greater weight loss alone identifies the clinically optimal therapy for every patient.
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Semaglutide strategy
Current U.S. indications for Wegovy include: chronic weight reduction and long-term weight maintenance; reduction of major adverse cardiovascular events in adults with established cardiovascular disease and overweight or obesity; and treatment of noncirrhotic MASH with F2–F3 fibrosis in adults. Match formulation and dose to the specific indication. Current U.S. labeling also includes oral Wegovy tablets for cardiovascular risk reduction and adult weight reduction; the MASH indication applies to Wegovy injection.
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Titrate according to indication and tolerability
Semaglutide injection Start 0.25 mg once weekly and escalate every 4 weeks: 0.25 → 0.5 → 1.0 → 1.7 mg → indication-specific maintenance dose. - CV risk reduction: 2.4 mg recommended; 1.7 mg may be used according to response/tolerability. - Adult weight reduction: 2.4 mg recommended; 1.7 mg may be used according to response/tolerability. - MASH F2–F3: 2.4 mg weekly; if not tolerated, reduce to 1.7 mg and consider subsequent re-escalation. Tirzepatide Start 2.5 mg once weekly for 4 weeks, then increase to 5 mg. Further increases may be made in 2.5-mg increments after ≥4 weeks at the current dose. - Weight management: maintenance 5, 10 or 15 mg weekly. - OSA: maintenance 10 or 15 mg weekly. Delay dose escalation when needed for tolerability.
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Monitor benefit beyond body weight
Reassess both weight-related and complication-specific outcomes. Monitor: body-weight trajectory and maintenance waist circumference and waist-to-height ratio glycemia and cardiometabolic risk factors target complication outcomes physical function and mobility quality of life treatment tolerability and adverse effects adherence and treatment burden Use complication-specific measures when relevant, such as OSA symptoms/AHI, glycemic measures or liver assessment.
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Is therapy providing clinically meaningful benefit?
Assess treatment response against the individualized goals established before therapy. Consider: magnitude and durability of weight reduction improvement in the target complication metabolic and cardiovascular health function and quality of life tolerability patient priorities Meaningful benefit + acceptable tolerability → continue. Insufficient benefit or unacceptable treatment burden → reassess strategy.
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Continue and individualize long-term therapy
Continue treatment when clinically meaningful benefit is sustained and treatment remains acceptable to the patient. Obesity/adiposity-based chronic disease generally requires long-term management. Continue lifestyle therapy and periodically reassess weight, complications, function, treatment burden and patient goals.
-
Reassess strategy if benefit or tolerability is inadequate
Reassess: adherence and treatment access dose and titration adverse effects weight-promoting medications untreated contributors or complications original treatment goal Consider slower titration, dose adjustment, switching therapy, use of another evidence-based anti-obesity medication, combination strategies when appropriate, or specialist referral.
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Consider metabolic/bariatric surgery when appropriate
Consider referral for metabolic/bariatric surgery according to current eligibility criteria, local guidance and patient preference. Current ASMBS/IFSO guidance recommends metabolic/bariatric surgery for BMI ≥35 kg/m² regardless of the presence or severity of obesity-related comorbidities. Surgery should also be considered in selected adults with BMI 30–34.9 kg/m² and metabolic disease, or when durable weight loss or improvement in obesity-related disease is not achieved with nonsurgical treatment.
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Tirzepatide strategy
Current U.S. indications for Zepbound include: chronic weight reduction and long-term weight maintenance in eligible adults; and treatment of moderate-to-severe obstructive sleep apnea in adults with obesity. Select the maintenance dose according to the indication, clinical response and tolerability.
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Titrate according to indication and tolerability
Semaglutide injection Start 0.25 mg once weekly and escalate every 4 weeks: 0.25 → 0.5 → 1.0 → 1.7 mg → indication-specific maintenance dose. - CV risk reduction: 2.4 mg recommended; 1.7 mg may be used according to response/tolerability. - Adult weight reduction: 2.4 mg recommended; 1.7 mg may be used according to response/tolerability. - MASH F2–F3: 2.4 mg weekly; if not tolerated, reduce to 1.7 mg and consider subsequent re-escalation. Tirzepatide Start 2.5 mg once weekly for 4 weeks, then increase to 5 mg. Further increases may be made in 2.5-mg increments after ≥4 weeks at the current dose. - Weight management: maintenance 5, 10 or 15 mg weekly. - OSA: maintenance 10 or 15 mg weekly. Delay dose escalation when needed for tolerability.
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Monitor benefit beyond body weight
Reassess both weight-related and complication-specific outcomes. Monitor: body-weight trajectory and maintenance waist circumference and waist-to-height ratio glycemia and cardiometabolic risk factors target complication outcomes physical function and mobility quality of life treatment tolerability and adverse effects adherence and treatment burden Use complication-specific measures when relevant, such as OSA symptoms/AHI, glycemic measures or liver assessment.
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Is therapy providing clinically meaningful benefit?
Assess treatment response against the individualized goals established before therapy. Consider: magnitude and durability of weight reduction improvement in the target complication metabolic and cardiovascular health function and quality of life tolerability patient priorities Meaningful benefit + acceptable tolerability → continue. Insufficient benefit or unacceptable treatment burden → reassess strategy.
-
Continue and individualize long-term therapy
Continue treatment when clinically meaningful benefit is sustained and treatment remains acceptable to the patient. Obesity/adiposity-based chronic disease generally requires long-term management. Continue lifestyle therapy and periodically reassess weight, complications, function, treatment burden and patient goals.
-
Reassess strategy if benefit or tolerability is inadequate
Reassess: adherence and treatment access dose and titration adverse effects weight-promoting medications untreated contributors or complications original treatment goal Consider slower titration, dose adjustment, switching therapy, use of another evidence-based anti-obesity medication, combination strategies when appropriate, or specialist referral.
-
Consider metabolic/bariatric surgery when appropriate
Consider referral for metabolic/bariatric surgery according to current eligibility criteria, local guidance and patient preference. Current ASMBS/IFSO guidance recommends metabolic/bariatric surgery for BMI ≥35 kg/m² regardless of the presence or severity of obesity-related comorbidities. Surgery should also be considered in selected adults with BMI 30–34.9 kg/m² and metabolic disease, or when durable weight loss or improvement in obesity-related disease is not achieved with nonsurgical treatment.