Table 3.

Pivotal Trials Results

Medication	Pivotal Trials	Weight Loss Observed in Trial	Additional Health Benefits
Orlistat	Xendos70	Mean weight loss at 4 years: 5.8 kg with orlistat vs 3.0 kg with placebo 52% completion rate with orlistat vs 34% with placebo	37.3% reduction in risk of developing type 2 diabetes Cumulative diabetes incidence: 6.2% with orlistat vs 9.0% with placebo
Phentermine	Kang et al 201071 Lewis et al 201958	Kang 2010 (12 weeks): Mean weight loss: 8.1 kg with phentermine vs 1.7 kg with placebo ≥5% weight loss: 95.8% vs 20.8%; ≥10% weight loss: 62.5% vs 4.7% Lewis 2019 (observational): Continuous use >12 months: 7.4% more weight loss at 24 months vs ≤3 months use	Kang 2010: Significant improvements in total cholesterol and LDL-C Improved waist circumference reduction Lewis 2019: No increased risk of cardiovascular disease or death with longer-term use
Phentermine-Topiramate	Equip, Conquer, Sequel59,60,72	EQUIP (56 weeks): 10.9% weight loss vs 1.6% in placebo CONQUER (56 weeks): 9.8% weight loss vs 1.2% in placebo SEQUEL (108 weeks): 10.5% weight loss vs 1.8% in plabeo	Significant improvements in waist circumference, blood pressure, fasting glucose Improved lipid profiles (triglycerides, total cholesterol, LDL, HDL) Decreased rates of incident diabetes
Naltrexone-Bupropion	COR-I, COR-II,61,73	COR-I (56 weeks): 6.1% weight loss vs 1.3% in placebo COR-II (56 weeks): 6.4% weight loss vs 1.2% in placebo weight loss ≥5% weight loss: 50.5% vs 17.1%	Improvements in cardiometabolic risk markers Improved weight-related quality of life Better control of eating Small reduction in blood pressure (~1 mm Hg) No increased depression or suicidality
Liraglutide	SCALE (Diabetes Mellitus) SCALE Obesity63,64	SCALE Diabetes (56 weeks): 6.0% (6.4 kg) weight loss vs 2.0% (2.2 kg) in placebo Scale Obesity (56 weeks): 8.4 kg weight loss vs 2.8 kg in placebo >10% weight loss: 33.1% vs 10.6%	Improved glycemic control in diabetes patients Improved metabolic parameters (triglycerides, cholesterol) Reduction in prediabetes progression Improvements in blood pressure and lipid profiles
Semaglutide	STEP 1–5 trials.65,74,75	STEP 1 (68 weeks): 14.9% weight vs 2.4% in placebo STEP 5 (104 weeks): 15.2% weight loss vs 2.6% in placebo STEP 8 vs Liraglutide (68 weeks): 15.8% weigh loss vs 6.4% in liraglutide	Improvements in waist circumference Reduced systolic blood pressure (3.9 mm Hg) Improved physical functioning scores Superior to liraglutide for weight loss Sustained weight loss with continued treatment
Tirzepatide	SURMOUNT and SURPASS67–69,76	SURMOUNT-1 (72 weeks): 15 mg: 20.9% weight loss vs 3.1% with placebo ≥20% weight loss: 57% (15 mg) vs 3% SURMOUNT-2 (T2D, 72 weeks): 15 mg: 14.7% weight loss vs 3.2% in placebo SURMOUNT-3 (after lifestyle): Additional 18.4% weight loss 87.5% achieved ≥5% additional loss	Improvements in all cardiometabolic measures In T2D: Mean HbA1c reduction of 2.34% (15 mg) Significant improvements in blood pressure, lipids Effective even after initial lifestyle intervention success