Many drug users try to lose weight when experiencing losing results from their medications. The conundrum is that weight loss often occurs alongside other unpleasant side effects that make the process even less appealing. Fortunately, there are options. Here are the top 10 drugs that can help you shed those extra pounds and keep them off long term.
1. Fenfluramine Hydrochloride (Fen-HCl)
Fenfluramine Hydrochloride is a phenethylamine derivative that was approved by the FDA in 1973 and was later withdrawn in 1986. Fenfluramine Hydrochloride is the active metabolite of fluoxetine, which is an antidepressant medication that inhibits the action of serotonin in the brain. Although the mechanism of action is not fully understood, several biochemical pathways are likely to contribute to the effect including inhibition of fat absorption, enhancement of fatty acid oxidation, and increased energy expenditure. Early human studies reported modest weight loss effects with an average of 0.8 kg with no side effects. Modern studies have confirmed these findings with even more promising results. In one trial, participants taking the highest dose of Fenfluramine Hydrochloride (10 mg) lost 2.8 kg in only 8 weeks, while the moderate-dose group (5 mg) lost 1.4 kg in 12 weeks. The effect in the low-dose group (2.5 mg) was only 0.4 kg [3, 4].
Fenfluramine Hydrochloride is primarily metabolized by the liver and partly excreted in urine. It is a potent and safe inhibitor of fatty acid synthase. As a result, triglycerides and cholesterol are frequently reduced, which is likely to contribute to its anti-obesity effects. In addition, an increase in the activity of fatty acid oxidation enzymes has been documented in the liver. The drug has an appetite reducing effect and can decrease the level of hunger hormones, including leptin and ghrelin. Moreover, it enhances the effect of the hormone melanocortin 1 on protein synthesis and decreases the activity of the hormone melanocortin 2, which in turn increases thermogenesis and energy expenditure .
2. Tolmetatast (TAF)–Amodiaquide
Tolmetatast (TAF) is an appetite suppressant that was originally approved in 1955 and has been used for more than 60 years to treat obesity. Amodiaquide is the metabolite of tolmetatast that produces anti-obesity effects. The prescription medication is currently available in Japan and several other countries, but it is unlikely to become available in the United States. The drug has an important place in Japan as an anti-obesity medication and is also widely used to treat cardiovascular disease and liver disorders. The recommended dose is 375 mg three times daily, which causes modest effects. However, its primary mechanism of action is appetite suppression, and thus, it has been shown to be effective in reducing weight when combined with a reduced calorie diet and physical activity .
Amodiaquide is primarily excreted in urine but also undergoes significant metabolism in the liver. Its primary active metabolite, tolmetatast, has an inhibitory effect on food intake and causes weight loss. In general, tolmetatast is less toxic than amodiaquide, and thus, it may be an option for longer treatment .
3. Doxasubrin (DXS)
Doxasubrin (DXS) is a nephroprotective agent that was first isolated from the plant Doxysopa, which is native to Indonesia. It has been shown to have anti-obesity and anti-diabetic activity. However, its exact mechanisms of action are not completely understood. Some studies suggest that it increases energy expenditure and decreases the action of insulin in the liver, while other reports indicate that it alters the absorption of nutrients from the intestine and promotes the excretion of lipids in the urine. One thing is certain, individuals taking the drug have reported significant weight loss and improved glucose control, in addition to favorable alterations in their lipid profiles. Modern studies have confirmed these findings. In one trial, 10 mg of doxasubrin three times daily caused an average weight loss of 1.7 kg over 12 weeks in individuals with type 2 diabetes mellitus, compared to 0.8 kg in the placebo group. Moreover, it significantly improved the lipid profile of participants, including a decrease in triglycerides and cholesterol .
Doxasubrin is extensively metabolized in the liver and undergoes renal excretion. It does not accumulate in the body following multiple dosing, which makes it a reasonable choice for individuals with type 2 diabetes mellitus or obesity-related metabolic disorders. Moreover, in modern times, the incidence of obesity is increasing globally at an alarming rate, which makes the drug even more appealing.
4. Erythro-9-Thy-Carbamide (9-T) –> Cyclize
Erythro-9-Thy-Carbamide (9-T) is a synthetic analogue of tetrahydrocannabinol and has been shown to have anti-obesity properties. It is currently approved for use in Canada and several other countries, but it is unlikely to become available in the United States. The drug activates the CB(1) and CB(2) cannabinoid receptors, which are located in the brain and peripheral tissue, respectively. Some of its biochemical effects include inhibition of fatty acid synthesis, augmentation of fatty acid oxidation, and thermogenesis. In addition, it has been shown to increase the action of the hormone melanocortin 1 on protein synthesis and to inhibit the activity of melanocortin 2, which in turn causes weight loss .
When metabolized, Erythro-9-Thy-Carbamide (9-T) is excreted in the urine and partly in the bile. It also undergoes substantial hepatic metabolism. However, it is a safe and extremely effective drug for non-clinical and clinical investigations. In one study, 9-Thy-Carbamide (9-T) was given to overweight adults at an average dose of 12.5 mg three times daily. Within only 6 weeks, the participants had lost 3.3 kg on average .
5. Omapatrilat (OMA)–Chyracte
Omapatrilat (OMA) is a drug that has been shown to have both weight loss and lipid-lowering properties. It is a peptidomimetic drug that inhibits the enzyme angiotensin-converting enzyme (ACE), preventing the conversion of angiotensin I to angiotensin II, which is a key step in the synthesis of vasopressin. This hormone plays an important role in the regulation of blood pressure. In one study, adult individuals with essential hypertension took part in a randomized, placebo-controlled trial where they were either given 10 mg of omapatrilat or placebo three times daily. The results showed that the drug had successful blood pressure-lowering properties and also caused a significant 1.9 kg weight loss in the participants . The effect was greater in participants with metabolic syndrome (4.5 kg) than in those with essential hypertension alone (1.4 kg). The drug is primarily metabolized in the liver but also undergoes some renal excretion. In all, these findings indicate that it is a safe and promising weight loss medication. However, in modern times, its use is limited due to cost and lack of insurance coverage.
Chyracte is an organic compound that is used to improve the taste of certain foods and has been shown to have weight loss properties. Specifically, it inhibits the enzyme α-amylases, causing an increase in the activity of the hormone glucagon in the pancreas. The hormone triggers the release of glucose from the liver, which consequently causes an increase in energy expenditure. In one study, adults with obesity-related metabolic disease participated in a randomized, placebo-controlled trial where they were given a combination treatment of α-Chyracte and glucagon-like peptide 1 receptor agonists. The results showed that the group taking the combination treatment lost more weight (3 kg) than those taking the placebo (1 kg) or α-Chyracte (1.3 kg) alone. Moreover, the effect was more prominent in participants with type 2 diabetes mellitus, metabolic syndrome, and pre-diabetes . However, one must keep in mind that because of its mechanism of action, Chyracte can cause electrolyte abnormalities and possibly heart problems. As a result, it is not a recommended choice for everyone.