Below is a more detailed look at the effectiveness of each of the anti-obesity medications.

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February 26, 2024

For employers seeking to align their weight management strategy with the latest evidence, this resource offers recommendations on creating a comprehensive benefits package to treat obesity, including behavior-based interventions and pharmacological and surgical treatment.

Below is a more detailed look at the effectiveness of each of the anti-obesity medications.

Liraglutide (Saxenda®)

Liraglutide was approved in 2014 as an anti-obesity medication after previously being on the market at a lower dose as an FDA-approved treatment for type 2 diabetes.1 Its efficacy in reducing weight and other risk factors has been evaluated in several clinical trials:

  • A 56-week study of adults with overweight or obesity without diabetes showed that those taking liraglutide lost 8.0% of their body weight, whereas patients in the placebo group lost 2.6%. Liraglutide treatment was also associated with reductions in cardiometabolic risk factors, including waist circumference, blood pressure and inflammatory markers.2
  • A second study of patients with overweight or obesity and diabetes demonstrated weight loss of 6.0% with a higher dose of liraglutide, 4.7% with a lower dose and 2.0% with placebo.3
  • In a third study of participants with overweight or obesity and comorbidities, weight decreased 6.2% among those who took liraglutide and 0.2% with placebo.4

Naltrexone HCl/bupropion HCl (Contrave®)

Approved in 2014, there have been several studies assessing the effective of naltrexone HCl/bupropion HCl on weight loss at 56 weeks:1

  • One study of adults with a BMI of 30-45 without comorbidities and a BMI 27-45 with dyslipidemia or hypertension showed a 6.1% decrease in body weight among those taking a higher dose of naltrexone HCl/bupropion HCl and a 5.0% decreaseamong those taking a lower dose, compared to 1.3% in the placebo group.5
  • Another study of adults with overweight and obesity showed greater weight loss among those who received the medication than those who didn’t (6.4% weight loss vs. 1.2%). The treatment group also saw greater improvements in various cardiometabolic risk markers, quality of life and control of eating.6
  • Efficacy was also assessed when the medication was used in conjunction with an intensive lifestyle intervention. Among those who participated in the intensive lifestyle intervention and took the medication, there was a weight reduction of 9.3% compared to 5.1% among those who only participated in the intensive lifestyle intervention.7 And among patients with overweight/obesity and diabetes, those who received the medication lost an average of 5% of their baseline weight compared to 1.8% among those who took the placebo. The medication also resulted in greater glycemic control and greater control of select cardiovascular risk factors.8

Orlistat (Xenical®)

A 4-year study of orlistat, a medication that received FDA approval in 1999, found that the medication produced greater weight loss and a reduction in the incidence of type 2 diabetes among those with obesity.1 Specifically, more patients who took orlistat achieved weight loss of ≥5% after 1 year and 4 years than those who did not (72.8% vs. 45.1% at 1 year and 52.8% and 37.3% at 4 years). Additionally, after 4 years of treatment, the cumulative incidence of diabetes was 6.2% among those who took orlistat and 9% for those who didn’t.9

Phentermine-topiramate (Qsymia®)

Several clinical trials have assessed the efficacy of phentermine-topiramate, which received approval from the FDA for the treatment of overweight and obesity in 2012:1

  • A study of patients with a BMI ≥ 35 found that after 56 weeks, those treated with a higher dose of phentermine- topiramate lost an average of 10.9% of their baseline body weight compared to 1.6% of those on placebo. Those on a lower dose of phentermine-topiramate lost 5.1%. Additional outcomes included improvements in cardiovascular and metabolic risk factors, like waist circumference, systolic blood pressure, and total cholesterol/HDL cholesterol ratio at both doses.10
  • A second study of patients with a BMI of 27-45 and two or more comorbidities found similar results: Those receiving the placebo lost 1.2% of their body weight, compared to 7.8% among those who received a lower dose and 9.8% among those who received a higher dose.11
  • A third study examined the long-term efficacy; at 108 weeks, those receiving placebo, a lower dose and a higher dose lost 1.8%, 9.3%, and 10.5% of their baseline weight, respectively. The study also found that those receiving the drug at higher and lower doses had improved cardiovascular and metabolic variables and decreased rates of incident diabetes in comparison with those taking the placebo.12

Semaglutide (Wegovy®)

The efficacy of semaglutide, a GLP-1 medication approved for the treatment of obesity in 2021, is well-established as is demonstrated through four clinical trials:

  • The largest trial showed that when semaglutide was used in conjunction with lifestyle changes, it led to an average 14.9% reduction in body weight after 68 weeks (more than 1.5X higher than the next best obesity drug). Importantly, study participants who took semaglutide also demonstrated greater improvement in cardiometabolic risk factors (i.e., BMI, waist circumference, blood pressure and lipid levels).13
  • A trial that combined semaglutide with intensive behavioral treatment showed similarly impressive outcomes. In adults with overweight or obesity without diabetes, a once-weekly injection of semaglutide in combination with intensive behavioral therapy and an initial low-calorie, meal-replacement program resulted in reductions in body weight of 16.0% compared to 5.7% among those who didn’t receive semaglutide.14
  • Another trial that assessed semaglutide’s efficacy in adults with overweight or obesity and type 2 diabetes found an average weight loss of 9.6% from baseline at week 68 compared to 3.4% of those in the placebo group.15
  • A fourth study of semaglutide assessed what happens when people with overweight or obesity stop or continue to take the medication after 20 weeks of being on it. At 20 weeks, the average weight loss among all study participants was 10.6%.16 Participants who were randomized to continue to take the medication for an additional 48 weeks lost even more weight, with an average of 17.4% at week 68 (interestingly, the study found that weight loss plateaued from week 60 to 68). Those who were randomized to stop taking semaglutide after 20 weeks gained weight but still had an average weight loss of 5% at week 68.16
  • Results from a SELECT trial also point to a decreased risk of major adverse cardiovascular events such as stroke, death and nonfatal myocardial infarction.17,18

Tirzepatide (Zepbound®)

Zepbound® - a medication that acts as a dual GLP-1 and GIP receptor agonist - surpasses other weight loss treatments currently on the market, as indicated by ongoing clinical research:

  • In a 72-week clinical trial known as SURMOUNT-1, individuals with obesity who were administered the maximum dosage of tirzepatide experienced an average weight loss of approximately 18%.19 Moreover, results from the SURMOUNT-1 trial of tirzepatide showed that in comparison to placebo doses, tirzepatide resulted in a greater percentage of reduction in weight.20
  • 1 | Tak YJ, Lee SY. Long-term efficacy and safety of anti-obesity treatment: Where do we stand? Curr Obes Rep. Mar 2021;10(1):14-30.  
  • 2 | Pi-Sunyer X, Astrup A, Fujioka K, et al. A randomized, controlled trial of 3.0 mg of liraglutide in weight management. New England Journal of Medicine. 2015;373(1):11-22.  
  • 3 | Davies MJ, Bergenstal R, Bode B, et al. Efficacy of liraglutide for weight loss among patients with type 2 diabetes: The SCALE diabetes randomized clinical trial. JAMA. 2015;314(7):687-699.
  • 4 | Wadden TA, Hollander P, Klein S, et al. Weight maintenance and additional weight loss with liraglutide after low-calorie-diet-induced weight loss: The SCALE Maintenance randomized study. International Journal of Obesity. 2013;37(11):1443-1451.
  • 5 | Greenway FL, Fujioka K, Plodkowski RA, et al. Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2010;376(9741):595-605.  
  • 6 | Apovian CM, Aronne L, Rubino D, et al. A randomized, phase 3 trial of naltrexone SR/bupropion SR on weight and obesity-related risk factors (COR-II). Obesity. 2013;21:935–43.  
  • 7 | Wadden TA, Foreyt JP, Foster GD, et al. Weight loss with naltrexone SR/bupropion SR combination therapy as an adjunct to behavior modification: the COR-BMOD trial. Obesity. 2011;19(1):110-20.  
  • 8 | Hollander P, Gupta AK, Plodkowski R, et al. Effects of naltrexone sustained-release/bupropion sustained-release combination therapy on body weight and glycemic parameters in overweight and obese patients with type 2 diabetes. Diabetes Care. 2013;36(12):4022-9.  
  • 9 | Torgerson JS, Hauptman J, Boldrin MN, Sjöström L. XENical in the prevention of diabetes in obese subjects (XENDOS) study: A randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care. 2004;27(1):155-161. 
  • 10 | Allison DB, Gadde KM, Garvey WT, et al. Controlled-release phentermine/topiramate in severely obese adults: a randomized controlled trial (EQUIP). Obesity. 2012;20(2):330-42. 
  • 11 | Gadde KM, Allison DB, Ryan DH, et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet. Apr 16 2011;377(9774):1341-52.  
  • 12 | Garvey WT, Ryan DH, Look M, et al. Two-year sustained weight loss and metabolic benefits with controlled-release phentermine/topiramate in obese and overweight adults (SEQUEL): a randomized, placebo-controlled, phase 3 extension study. Am J Clin Nutr. Feb 2012;95(2):297-308.  
  • 13 | Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity. NEJM. 2021;384(11):989-1002. 
  • 14 | Wadden TA, Bailey TS, Billings LK, et al. Effect of subcutaneous semaglutide vs placebo as an adjunct to intensive behavioral therapy on body weight in adults with overweight or obesity: The STEP 3 randomized clinical trial. JAMA. 2021;325(14):1403-1413.  
  • 15 | Davies M, Færch L, Jeppesen OK, et al. Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. Lancet. 2021;13(397):971-984.  
  • 16 | Rubino D, Abrahamsson N, Davies M, et al. Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity: the STEP 4 randomized clinical trial. JAMA. 2021;325(14):1414-1425.  
  • 17 | Saha A. Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity - SELECT. American College of Cardiology.,and%20stroke%20compared%20with%20placebo. Accessed December 3, 2023.  
  • 18 | Reuters. Novo Nordisk to present new data from weight-loss, diabetes trials. November 7, 2023. Accessed December 19, 2023.  
  • 19 | Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity. New England Journal of Medicine. 2022;387(3):205-216. doi:10.1056/nejmoa2206038 
  • 20 | Institute for Clinical and Economic Review (ICER). Medications for obesity management: Effectiveness and value. October 20, 2022. Accessed October 20, 2023.

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