Integrating semaglutide into obesity management – a primary care perspective

Figures & data

Video 1

Integrating Semaglutide Into Obesity Management

Figure 1. Framework for initial and ongoing discussions with patients as part of individualized obesity management [3–6,13,15–18].

BMI, body mass index.

Table 1. FDA-approved pharmacotherapies for long-term weight management.

Medication	Orlistat [46]	Phentermine/topiramate ER [47]	Bupropion/naltrexone [48]	Liraglutide [49]	Semaglutide [36]
Commercial name	XENICAL®	QSYMIA®	CONTRAVE®	SAXENDA®	WEGOVY®
Mechanism of action	Gastrointestinal lipase inhibitor	Noradrenergic + GABA receptor activator, kainite/AMPA glutamate receptor inhibitor	Opioid receptor antagonist + dopamine/norepinephrine reuptake inhibitor	GLP-1RA	GLP-1RA
Route of administration	Oral	Oral	Oral	Subcutaneous	Subcutaneous
1-year weight change relative to placebo, kg (95% CI)^a	Adults: –3.4 kg (–3.2 to –3.6) Adolescents: –2.6 kg	For 7.5/46 mg/d: –6.7 kg (–5.9 to –7.5) For 15/92 mg/d: –8.9 kg (–8.3 to –9.4)	–4.9 kg (–4.6 to –5.1)	Adults: –5.2 kg (–4.9 to –5.6) Adolescents: –4.5 kg (–7.2 to –1.8)	–6.1 kg to –12.7 kg
Indication	In conjunction with a reduced-calorie diet for the treatment of people with BMI ≥30 kg/m^2, or ≥27 kg/m^2 with associated risk factors (hypertension, diabetes or dyslipidemia)	As an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with a BMI of ≥30 kg/m^2 or ≥27 kg/m^2 in the presence of at least one weight-related comorbidity (e.g. hypertension, T2D, or dyslipidemia)	As an adjunct to a reduced-calorie diet and increased physical activity for weight management in adults with an initial BMI of ≥30 kg/m^2 or ≥27kg/m^2 to <30 kg/m^2 in the presence of at least one weight-related comorbidity (e.g. T2D, dyslipidemia, or controlled hypertension)	As an adjunct to a reduced-calorie diet and increased physical activity for weight management in adults with an initial BMI of ≥30 kg/m^2 or ≥27 kg/m^2 to <30 kg/m^2 in the presence of at least one weight-related comorbidity, (e.g. dysglycemia [prediabetes or T2D], hypertension, dyslipidemia, or obstructive sleep apnea)	As an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial BMI of ≥30 kg/m^2 or ≥27 kg/m^2 in the presence of at least one weight-related comorbidity (e.g. hypertension, T2D, or dyslipidemia)
Contraindications	Pregnancy; chronic malabsorption syndrome; cholestasis; breastfeeding	Pregnancy; glaucoma; hyperthyroidism; during or within 14 days of taking monoamine oxidase inhibitors	Pregnancy; uncontrolled hypertension; current seizure disorder or a history of seizures; known central nervous system tumor; acute alcohol or benzodiazepine withdrawal; history of bipolar disorder; concomitant treatment containing bupropion or naltrexone; current or previous diagnosis of bulimia or anorexia nervosa; dependent on chronic opioids or opiate agonists (e.g. methadone) or in acute opiate withdrawal; concomitant administration of MAOI; severe hepatic impairment; end-stage renal failure	Pregnancy; a personal or family history of MTC or MEN 2; hypersensitivity to liraglutide or to any of the excipients	Pregnancy; a personal or family history of MTC or in patients with MEN 2; prior serious hypersensitivity reactions to semaglutide or to any of the excipients
Common side effects	Gastrointestinal events	Paresthesia; dizziness; dysgeusia; insomnia; constipation; dry mouth	Nausea; constipation; vomiting; dizziness; dry mouth	Gastrointestinal events	Gastrointestinal events
Notes	Discontinue after 12 weeks if patients have been unable to lose at least 5% of body weight [46]	The effect of Qsymia on cardiovascular morbidity and mortality has not been established	Discontinue after 12 weeks if patients have been unable to lose at least 5% of body weight	Discontinue after 16 weeks if patients have been unable to lose at least 4% of body weight	Discontinue if patients cannot tolerate the 2.4 mg dose

^aWeight changes relative to placebo (95% CI) using intent-to-treat analyses for each medication at 1 year for orlistat, phentermine-topiramate, naltrexone-bupropion-ER, and liraglutide are found in prior reports that performed meta-analyses [50–53]. At present, there is only one large, placebo-controlled trial for adolescents using liraglutide [54]. Semaglutide weight change is described in the papers as occurring at week 68, after 52 weeks at full dose [42,55,56]. Total weight losses (not relative to placebo) are somewhat greater and generally reflect the intensity of the lifestyle modification program offered.

AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid; BMI, body mass index; CI, confidence interval; d, day; EMA, European Medicines Agency; ER, extended-release; FDA, US Food and Drug Administration; GABA, gamma-aminobutyric acid; GLP-1RA, glucagon-like peptide-1 receptor agonist; MAOI, monoamine oxidase inhibitor; MEN 2, multiple endocrine neoplasia syndrome type 2; MTC, medullary thyroid carcinoma; T2D, type 2 diabetes.

Figure 2. Key considerations for integrating semaglutide 2.4 mg into obesity management [41].

BMI, body mass index; GLP-1RA, glucagon-like peptide-1 receptor agonist; MTC, medullary thyroid carcinoma; MEN 2, multiple endocrine neoplasia syndrome type 2; T2D, type 2 diabetes.

Figure 3. Once-weekly semaglutide 2.4 mg dosing schedule [43].

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