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. 2021 May 11;38(6):2821–2839. doi: 10.1007/s12325-021-01710-0

Table 1.

Mechanism of action and efficacy of anti-obesity medications currently available in the USA [10, 21, 23, 37, 39, 43, 46, 47, 57, 6265, 6978]

Anti-obesity medication Type of agent/mechanism of action [23] Trial information Percentage of patients achieving categorial weight loss at 1 year
 ≥ 5%
(or > 5%)
≥ 10%
(or > 10%)
Percentage of patients achieving weight loss maintenance at 2 years
Liraglutide

· GLP-1RA

· Reduces appetite and food cravings [21]

· Increases satiety

· Alters food preference and reward pathways [21]

Astrup et al., 2009; Astrup et al., 2012: placebo-controlled, randomized, 20-week trial for liraglutide (1.2, 1.8, 2.4, and 3.0 mg QD) with open-label comparator (orlistat 120 mg TID) + 84-week extension in patients with BMI 30–40 kg/m2

Patients were on a 500-kcal/day energy-deficient diet and increased their physical activity

(Liraglutide 3.0 mg; orlistat; placebo)

73%; 44%; 28%

(liraglutide vs. placebo or orlistat, p ≤ 0.0001)

(Liraglutide 3.0 mg; orlistat; placebo)

37%; 14%; 10%

(Liraglutide 2.4/3.0 mg vs. orlistat)

≥ 5% weight loss: 52% vs. 29% (p < 0.001)

 ≥ 10% weight loss: 26% vs. 16% (p = 0.04)

Pi-Sunyer et al., 2015: placebo-controlled, double-blind, randomized, 56-week trial of liraglutide 3.0 mg QD in patients with BMI ≥ 30 kg/m2 (or ≥ 27 kg/m2 with dyslipidemia or hypertension)

Patients received counseling on lifestyle modification

(Liraglutide 3.0 mg; placebo)

63%; 27% (p < 0.001)

(Liraglutide 3.0 mg; placebo)

33%; 11% (p < 0.001)

NR

Davies et al., 2015: placebo-controlled, randomized, double-blind, parallel-group 56-week trial of liraglutide 1.8 and 3.0 mg QD in patients with BMI ≥ 27 kg/m2 with diabetes taking 0–3 OADs

Patients were on a 500-kcal/day energy-deficient diet and increased their physical activity

(Liraglutide 3.0 mg; placebo)

54%; 21% (p < 0.001)

(Liraglutide 3.0 mg; placebo)

25%; 7% (p < 0.001)

NR

Wadden et al., 2013: placebo-controlled, double-blind, randomized, 56-week trial of liraglutide 3.0 mg QD in patients with BMI ≥ 30 (or ≥ 27 with comorbidity) kg/m2 after low-calorie-diet-induced weight loss

Patients received diet and exercise counseling

(Liraglutide 3.0 mg; placebo)a

51%; 22% (p < 0.0001)

(Liraglutide 3.0 mg; placebo)a

26%; 6% (p < 0.0001)

NR
Wadden et al., 2020b: placebo-controlled, double-blind, randomized, 56-week trial of liraglutide 3.0 mg QD plus IBT in patients with BMI ≥ 30 kg/m2

(Liraglutide 3.0 mg; placebo)

62%; 34% (p = 0.0003)

(Liraglutide 3.0 mg; placebo)

31%; 20% (p = 0.0469)

NR
Garvey et al., 2020: placebo-controlled, double-blind, randomized, 56-week trial of liraglutide 3.0 mg QD plus IBT in patients with BMI of ≥ 27 kg/m2 and diabetes treated with basal insulin and ≤ 2 OADs

(Liraglutide 3.0 mg; placebo)

52%; 24.0% (p < 0.0001)

(Liraglutide 3.0 mg; placebo)

23%; 7% (p < 0.0001)

NR
Naltrexone-bupropion

· Naltrexone: opioid antagonist

· Bupropion: aminoketone antidepressant [62]

⋅ Suppresses appetite

Greenway et al., 2010: placebo-controlled, double-blind, randomized, 56-week trial of naltrexone-bupropion (NB16 and NB32b) BID in patients with BMI ≥ 30 (or ≥ 27 with comorbidity) to 45 kg/m2

Patients were on a mild hypocaloric diet and exercise

(NB16; NB32; placebo)

39%; 48%; 16% (NB16/NB32 vs. placebo, both p < 0.0001)

(NB16; NB32; placebo)

20%; 25%; 7% (NB16/NB32 vs. placebo, both p < 0.0001)

NR

Apovian et al., 2013: placebo-controlled, double-blind, randomized, 56-week trial of naltrexone-bupropion (NB32) BID in patients with BMI ≥ 30 (or ≥ 27 with controlled hypertension and/or dyslipidemia) to 45 kg/m2

Patients were on a 500-kcal/day energy-deficient diet, increased physical activity, and behavioral modification advice

(NB32; placebo)

51%; 17% (p < 0.001)

(NB32; placebo)

28%; 6% (p < 0.001)

NR
Wadden et al., 2011: placebo-controlled, double-blind, randomized, 56-week trial of naltrexone-bupropion (NB32) QD and BMOD in patients with BMI ≥ 30 (or ≥ 27 with controlled hypertension and/or dyslipidemia) to 45 kg/m2

(NB32; placebo)

66%; 43% (p < 0.001)

(NB32; placebo)

42%; 20% (p < 0.001)

NR

Hollander et al., 2013: placebo-controlled, double-blind, randomized, 56-week trial of naltrexone-bupropion (NB32) QD in patients with BMI ≥ 27 and ≤ 45 kg/m2 and type 2 diabetes treated with or without OADs

Patients were on a 500-kcal/day energy-deficient diet, dietary counseling and advice on behavioral modification, including instructions to increase physical activity

(NB32; placebo)

45%; 19% (p < 0.001)

(NB32; placebo)

19%; 6% (p < 0.001)

NR
Orlistat

· Reversible inhibitor of gastrointestinal lipases [65]

· Inhibits fat absorption

Hauptman et al., 2000: placebo-controlled, double-blind, randomized, 2-year trial of orlistat (60 and 120 mg TID) in patients with BMI 30–44 kg/m2

Patients were on an energy-deficient diet

(Orlistat 60 mg; orlistat 120 mg; placebo)

49%; 51%; 31%

(Orlistat 60 mg/120 mg vs. placebo, both p < 0.001)

(Orlistat 60 mg; orlistat 120 mg; placebo)

24%; 29%; 11%

(Orlistat 60 mg/120 mg vs. placebo, both p < 0.001)

(Orlistat 60 mg; orlistat 120 mg; placebo)

≥ 5% weight loss: 34%; 34%; 24%

(Orlistat 60 mg vs. placebo: p = 0.03; orlistat 120 mg vs. placebo: p = 0.02)

≥ 10% weight loss: 15%; 19%; 7%

(Orlistat 60 mg vs. placebo: p = 0.008; orlistat 120 mg vs. placebo: p = 0.001)

Rössner et al., 2000: placebo-controlled, double-blind, randomized, 2-year trial of orlistat (60 and 120 mg) TID in patients with BMI 28–43 kg/m2

Patients were on a 600-kcal/day energy-deficient diet

NR

(Orlistat 60 mg; orlistat 120 mg; placebo)

31%; 38%; 19%

(Orlistat 60 mg vs. placebo: p = 0.002; orlistat 120 mg vs. placebo: p = 0.001)

(Orlistat 60 mg; orlistat 120 mg; placebo)

 > 10% weight loss: 29%; 28%; 19%

(Orlistat 60 mg/120 mg vs. placebo: both p < 0.05)

Phentermine

· Phentermine: sympathomimetic amine anorectic [63]

· Suppresses appetite

Kang et al., 2010: placebo-controlled, double-blind, randomized, 12-week trial of phentermine 30 mg QD in patients with obesity and controlled diabetes, hypertension, and dyslipidemia

(Phentermine; placebo)

96%; 21% (p < 0.001)

(Phentermine; placebo)

63%; 5% (p < 0.001)

NR
Phentermine-topiramate

· Phentermine: sympathomimetic amine anorectic [64]

· Topiramate: anti-epileptic drug

· Suppresses appetite

Allison et al., 2012: placebo-controlled, randomized, 56-week trial of PT (3.75/23 mg or 15/92 mg) QD added to a reduced-energy diet in patients with BMI ≥ 35 kg/m2

Patients were advised to follow a 500-kcal/day energy-deficient diet and received standardized diet and lifestyle-modification counseling

(PT 3.75/23 mg; PT 15/92 mg; placebo)

45%; 67%; 17%

(PT 3.75/23 mg/15/92 mg vs. placebo, both p < 0.0001)

(PT 3.75/23 mg; PT 15/92 mg; placebo)

19%; 47%; 3%

(PT 3.75/23 mg/15/92 mg vs. placebo, both p < 0.0001)

NR

Gadde et al., 2011; Garvey et al., 2012: placebo-controlled, double-blind, randomized, 108-week trial of PT (7.5/46 mg or 15/92 mg) QD in patients with BMI 27–45 kg/m2 and cardiometabolic disease

Patients received standardized diet and lifestyle-modification counseling

(PT 7.5/46 mg; PT 15/92 mg; placebo)

62%; 70%; 21%

(PT 5/46 mg/15/92 mg vs. placebo, both p < 0.0001)

(PT 7.5/46 mg; PT 15/92 mg; placebo)

37%; 48%; 7%

(PT 5/46 mg/15/92 mg vs. placebo, both p < 0.0001)

(PT 7.5/46 mg; PT 15/92 mg; placebo)

≥ 5% weight loss: 75%; 79%; 30%

 ≥ 10% weight loss: 50%; 54%; 12%

(PT 7.5/46 mg/15/92 mg vs. placeb, both p < 0.0001)

Percentages are rounded up to one decimal place

BID two times a day, BMI body mass index, BMOD intensive behavior modification, GLP-1RA glucagon-like peptide 1 receptor agonist, IBT intensive behavioral therapy, NR not reported, OAD oral antihyperglycemic drug, PT phentermine-topiramate, QD once-daily, TID three times per day

aBased on patients achieving ≥ 5% weight loss during the run-in period

bNB16: sustained-release naltrexone 16 mg per day plus sustained-release bupropion 360 mg per day combined in fixed-dose tablets; NB32: sustained-release naltrexone 32 mg per day plus sustained-release bupropion 360 mg per day combined in fixed-dose tablets