Table 1.
Efficacy and safety of currently available long-term anti-obesity drugs for obesity
| Drug | Year of approval | Trial (study duration) | Maximum dose | Mean weight loss from baseline | Proportion of patients losing >5% (10%) of baseline weighta | HbA1c change, %b | Lipid profiles change, %b | SBP/DBP change, mm Hgb | Heart rate change, beats/minc | Common adverse effects | Contraindication | Reference |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Orlistat | 1999 | XENDOS (208 wk) | 120 mg three times daily | 2.8 kg | 52.8% vs. 37.3% in placebo (26.2% vs. 15.6% in placebo) |
- | TC, −7.5 LDL-C, −9.8 HDL-C, −5.1 TGs, non-significant |
−2.1/−1.0 | No change | Loose, oily stools, fecal incontinence, flatus | Pregnancy, cholestasis, malabsorption syndrome | [17] |
|
| ||||||||||||
| Phentermine/Topiramate ER | 2012 | EQUIP (56 wk) | 15/92 mg | 10.9% | 66.7% vs. 17.3% in placebo (47.2% vs. 7.4% in placebo) |
- | TC, −2.5 LDL-C, −2.9 HDL-C, 3.5 TGs, −14.3 |
−3.8/−1.9 | 1.6 | Dry mouth, paresthesia, insomnia, depression, anxiety | Pregnancy, uncontrolled hypertension, cardiovascular disease, chronic kidney disease, glaucoma, hyperthyroidism, during or within 14 days of treatment with MAOIs | [38] |
| CONQUER (56 wk) | 15/92 mg | 12.4% | 70.0% vs. 21.0% in placebo (48.0% vs. 7.0% in placebo) |
−0.2 | TC, −3.0 LDL-C, −2.8 HDL-C, 5.6 TGs, −15.3 |
−3.2/−1.1 | [37] | |||||
| SEQUEL (104 wk) | 15/92 mg | 10.5% | 79.3% vs. 30.0% in placebo (53.9% vs. 11.5% in placebo) |
−0.2 | TC, non-significant LDL-C, 5.0 HDL-C, 7.7 TGs, −14.5 |
Non-significant | [45] | |||||
|
| ||||||||||||
| Naltrexone SR/Bupropion SR | 2014 | COR-I (56 wk) | 32/360 mg | 6.1% | 48% vs. 16% in placebo (25% vs. 7.0% in placebo) |
- | TC, non-significant LDL-C, non-significant HDL-C, 7.2 TGs, −6.1 |
−0.4/−0.1 | 1.1 (COR-I) | Nausea, dry mouth, constipation, headache, dizziness | Pregnancy, uncontrolled hypertension, seizure, any opioid use, abrupt dis-continuation of alcohol, concomitant administration of MAOIs, severe hepatic impairment, end-stage renal failure | [28] |
| COR-II (56 wk) | 32/360 mg | 6.4% | 50.5% vs. 17.1% in placebo (28.3% vs. 5.7% in placebo) |
- | TC, non-significant LDL-C, 0.03 HDL-C, 0.1 TGs, −9.3 |
1.1/non-significant | [29] | |||||
| COR-BMOD (56 wk) | 32/360 mg | 9.3% | 66.4% vs. 42.5% in placebo (41.5% vs. 20.2% in placebo) |
- | TC, non-significant LDL-C, −2.9 HDL-C, 6.6 TGs, −8.1 |
2.6/1.4 | [30] | |||||
| COR-Diabetes (56 wk) | 32/360 mg | 5.0% | 44.5% vs. 18.9% in placebo (18.5% vs. 5.7% in placebo) |
−0.5 | TC, non-significant LDL-C, non-significant HDL-C, 3,3 TGs, −10.4 |
Non-significant | [31] | |||||
|
| ||||||||||||
| Liraglutide | 2015 | SCALE-Sleep Apnea (32 wk) | 3.0 mg | 5.7% | 46.3% vs. 18.5% in placebo (23.4% vs. 1.7% in placebo) |
−0.2 | Non-significant | −4.1/non-significant | 2.4 (SCALE-Obesity and prediabetes) | Nausea, vomiting, constipation, diarrhea | Pregnancy, history of pancreatitis, personal/family history of medullary thyroid cancer or MEN2 syndrome | [44] |
| SCALE-Diabetes (56 wk) | 3.0 mg | 6.0% | 54.3% vs. 21.4% in placebo (25.2% vs. 6.7% in placebo) |
−1.0 | TC, −4.3 LDL-C, non-significant HDL-C, non-significant TGs, −15.1 |
−2.4/non-significant | [42] | |||||
| SCALE-Obesity and prediabetes (56 wk) | 3.0 mg | 8.0% | 63.2% vs. 27.1% in placebo (33.1% vs. 10.6% in placebo) |
−0.23 | TC, −2.3 LDL-C, −2.4 HDL-C, 1.9 TGs, −9.3 |
−2.8/−0.9 | [41] | |||||
| SCALE-Maintenance (56 wk) | 3.0 mg | 6.2% | 50.5% vs. 21.8% in placebo (26.1% vs. 6.3% in placebo) |
−0.3 | Non-significant | −2.7/non-significant | [43] | |||||
HbA1c, glycosylated hemoglobin; SBP, systolic blood pressure; DBP, diastolic blood pressure; XENDOS, Xenical in the Prevention of Diabetes in Obese Subjects; TC, total cholesterol; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; TG, triglyceride; ER, extended-release; EQUIP, controlled-release phentermine/topiramate in severely obese adults: a randomized controlled trial; MAOI, monoamine oxidase inhibitor; CONQUER, Controlled-Release Phentermine plus Topiramate Combination in Overweight and Obese Adults; SEQUEL, 2-year Sustained Weight Loss and Metabolic Benefits with Controlled-release Phentermine/Topiramate in Obese and Overweight Adults; SR, sustained-release; COR, Contrave Obesity Research; BMOD, behavior modification; SCALE, Satiety and Clinical Adiposity—Liraglutide Evidence in Nondiabetic and Diabetic Individuals; MEN, multiple endocrine neoplasia.
Treatment vs. placebo,
Placebo-subtracted,
Treatment from baseline.