Lorcaserin
A selective 5-HT2C receptor agonist marketed as Belviq, approved by the FDA in 2012 for chronic weight management. Designed to avoid the 5-HT2B valvulopathy of older serotonergic anorectics, it was nonetheless withdrawn in 2020 after a long-term trial suggested a small excess of cancer.
01 Overview
Lorcaserin was engineered for selectivity at the 5-HT2C receptor, which mediates serotonergic appetite suppression, while sparing the 5-HT2B receptor responsible for fenfluramine's heart-valve damage. It produced roughly 3 kg of placebo-subtracted weight loss and the cardiovascular-outcomes CAMELLIA-TIMI 61 trial found no excess cardiac valvulopathy or major adverse cardiac events.
However, a pooled analysis of that trial's long-term data showed a small but statistically notable increase in cancer diagnoses in lorcaserin-treated patients. In February 2020 the FDA requested market withdrawal on the basis that the potential cancer risk outweighed the modest weight-loss benefit.
02 Mechanism
Selective 5-HT2C receptor agonist that activates pro-opiomelanocortin (POMC) neurons in the hypothalamus to promote satiety, with low affinity for the 5-HT2B receptor.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Former therapeutic dose | 20 mg/day | Oral | 10 mg twice daily or 20 mg XR once daily; withdrawn 2020. |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Weight lossModest, sustained weight reduction via enhanced satiety. | ~3 kg vs placebo/year | Clinical | |
| Improved glycaemiaSecondary metabolic benefit in type 2 diabetes. | small HbA1c reduction | Clinical |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Possible increased cancer incidencePooled long-term data showed more cancer diagnoses on lorcaserin, prompting withdrawal. | Severe | Small excess (CAMELLIA-TIMI 61) | Clinical | |
| Headache and dizzinessHeadache, dizziness, fatigue and nausea, especially early. | Mild | Common | Clinical |