Table 2.
A Summary of Anti-Obesity Drug Trials
| Drug | Trials | FDA Approval | EMA Approval | Cardiovascular Safety | Weight Loss | Reason for Withdrawal | Comments |
|---|---|---|---|---|---|---|---|
| Anti-obesity medications | |||||||
| Phentermine/topiramate | CONQUER SEQUEL AQCLAIM |
Yes (2012) | No | Statistically power was not enough to measure cardiovascular safety | Significant weight loss | EMA: Lacked support for long-term CV safety; concerns over cognitive and harmful psychiatric events; potential for abuse | - Showed the most robust decrease in weight loss compared with other anti-obesity medications. - Showed troubling adverse events, such as psychiatric and cognition problems. |
| Naltrexone/bupropion | LIGHT CONVENE |
Yes (2014) | Yes (2015) | Statistical power was not enough to measure cardiovascular safety | Significant weight loss | NA | - It can cause elevation of BP and heart rate, making it challenging to prescribe to patients with significant CVD. - The failure of not only one but two CVOTs to illuminate the cardiovascular safety of the naltrexone/bupropion combination represents a significant setback. |
| T2DM medications | |||||||
| Liraglutide | LEADER | Yes (2014) | Yes (2015) | 1.8 mg (dose) Superiority 3.0 mg (dose) NA |
1.8 mg caused modest weight loss 3.0 mg caused significant weight loss |
NA | - The applicability of liraglutide 3.0 mg in terms of cardiovascular superiority remains unknown. |
| Semaglutide | SUSTAIN-6 PIONEER6 |
Yes (2019) | Yes (2019) | Non-inferiority | Significant weight loss | NA | |
| SGLT2 inhibitor | EMPA-REG CANVAS DAPA-HF |
Yes (2014) Yes (2013) Yes (2020) |
Yes (2014) Yes (2013) Yes (2020) |
Superiority Superiority Non-inferiority |
Modest weight loss (2 kg) | NA NA NA |
- SGLT-2 inhibitors successfully showed superiority in 3-point MACE and heart failure hospitalisation. - Weight loss effect was minimal |
Abbreviations: BP, blood pressure; CV, cardiovascular; CVD, cardiovascular disease; CVOT, cardiovascular outcome trial; EMA, European Medicines Agency; FDA, Food and Drug Administration; HR, hazard ratio; MACE, major adverse cardiovascular events; NA, not available; SGLT2, sodium-glucose co-transporter-2; T2DM, type 2 diabetes mellitus.