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
In adults with established cardiovascular disease and overweight or obesity, semaglutide has an FDA indication to reduce the risk of cardiovascular death, nonfatal myocardial infarction and nonfatal stroke. This is a complication-specific cardiovascular indication, not simply an extrapolation from weight loss.
-
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 OSA with obesity
Tirzepatide is FDA-approved for treatment of moderate-to-severe obstructive sleep apnea in adults with obesity, together with reduced-calorie diet and increased physical activity. For the OSA indication, the recommended maintenance dose is 10 mg or 15 mg once weekly.
-
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 is FDA-approved for treatment of adults with noncirrhotic MASH and moderate-to-advanced fibrosis consistent with stages F2–F3. The indication received accelerated approval based on improvement in MASH and fibrosis and remains subject to confirmatory evidence requirements.
-
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
When type 2 diabetes or glycemic control is a major treatment goal, consider the glucose-lowering efficacy, expected weight effect, cardiovascular and renal profile, concomitant glucose-lowering therapy and hypoglycemia risk. Coordinate obesity pharmacotherapy with the patient's diabetes treatment plan and product-specific indications.
-
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
For other obesity-related complications, select therapy according to the strength of evidence for the relevant clinical outcome together with expected weight reduction, safety, tolerability and patient preference. Do not describe a complication-specific FDA indication unless one exists for that drug and clinical setting.
-
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.
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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
When no single complication predominates, individualize therapy according to: expected weight-reduction efficacy safety and contraindications route and treatment burden tolerability cost and access patient preferences and goals
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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.
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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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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.
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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.