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AGA Clinical Practice Guideline on Pharmacological Interventions for Adults With Obesity, 2022

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Indications

Adults with BMI ≥30 kg/m² (obesity)
Adults with BMI ≥27 kg/m² with weight-related complications, such as:
- Type 2 diabetes mellitus (T2DM)
- Hypertension
- Dyslipidemia
- Obstructive sleep apnea
- Cardiovascular disease

Contraindications

Pregnancy is a consistent contraindication across all agents.
Eating disorders: Avoid use in patients with active bulimia nervosa binge eating disorder.
Combination use: Avoid using GLP-1 RAs with DPP-4 inhibitors or other GLP-1 RAs.

BWL target and benefit

Total body weight loss (TBWL) – clinically meaningful	≥5%	Associated with significant improvements in cardiometabolic risk factors.
Total body weight loss (TBWL) – high-efficacy target	≥10%	Linked to even greater long-term health benefits.

GLP-1 RA

Mechanism of Action

GLP-1 is a natural hormone secreted by intestinal L-cells in response to food intake
GLP-1 receptors are widely expressed (pancreas, GI tract, brain, heart, thyroid, etc.)
Effects include:
- Glucose-dependent insulin secretion
- Delayed gastric emptying
- Reduced food intake desire
- β-cell modulation

Efficacy

Semaglutide(RCTs reviews, vs. placebo)

Category	Value
Mean difference in %TBWL	10.76%
Mean absolute weight loss (MD)	10.81 kg
RR for ≥5% TBWL	2.74 (95% CI: 2.21–3.40)
RR for ≥10% TBWL	5.25 (95% CI: 3.61–7.64)
RR for ≥15% TBWL	7.82 (95% CI: 5.19–11.76)

Liraglutide(RCTs reviews, vs. placebo)

Category	Value
Mean difference in %TBWL	4.81%
Mean absolute weight loss (MD)	5.3 kg
RR for ≥5% TBWL	2.09 (95% CI: 1.80–2.42)
RR for ≥10% TBWL	2.67 (95% CI: 2.14–3.34)
RR for ≥15% TBWL	3.04 (95% CI: 2.25–4.12)