From the Guidelines
Tesofensine is not currently recommended for treating obesity or Alzheimer's disease as it has not received regulatory approval for these conditions in most countries. The drug, which works by inhibiting the reuptake of neurotransmitters (norepinephrine, dopamine, and serotonin), has shown promise in clinical trials for weight loss, with studies demonstrating significant weight reduction compared to placebo 1. However, it remains an investigational compound. For obesity, standard approved treatments include lifestyle modifications, FDA-approved medications like phentermine-topiramate, liraglutide, or semaglutide, and in some cases, bariatric surgery 1. For Alzheimer's disease, cholinesterase inhibitors and memantine are the approved pharmacological options, along with supportive care 1. While tesofensine showed initial promise for neurodegenerative disorders, research has not supported its efficacy for Alzheimer's treatment. Patients interested in emerging treatments should consult healthcare providers about clinical trials or approved alternatives rather than seeking tesofensine.
Some key points to consider:
- The American Gastroenterological Association recommends adding pharmacological agents to lifestyle interventions for adults with obesity or overweight with weight-related complications who have had an inadequate response to lifestyle interventions alone 1.
- The FDA has approved several medications for chronic weight management, including phentermine-topiramate, liraglutide, and semaglutide 1.
- Cholinesterase inhibitors and memantine are the primary pharmacological treatments for Alzheimer's disease, with a focus on managing symptoms and slowing disease progression 1.
- Patients should prioritize approved treatments and consult with healthcare providers before seeking investigational compounds like tesofensine.
In terms of treatment options, the following are recommended:
- For obesity: lifestyle modifications, phentermine-topiramate, liraglutide, semaglutide, and bariatric surgery 1.
- For Alzheimer's disease: cholinesterase inhibitors, memantine, and supportive care 1.
It is essential to note that tesofensine is not approved for use in these conditions, and patients should focus on established treatments with proven efficacy and safety profiles.
From the Research
Recommended Use of Tesofensine
The recommended use of tesofensine in treating obesity and Alzheimer's disease is based on its efficacy as a triple monoamine reuptake inhibitor, which inhibits noradrenaline, 5-HT, and dopamine reuptake.
- Tesofensine has been shown to produce significant weight loss in obese patients, with a mean weight reduction of 4.5,9.2, and 10.6% higher than that of placebo for 0.25,0.5, and 1.0 mg, respectively 2, 3.
- The drug has also been found to induce appetite suppression and weight loss with reversal of low forebrain dopamine levels in the diet-induced obese rat, suggesting that its anti-obesity effects are associated with positive modulation of central dopaminergic activity 4.
- In patients with Alzheimer's disease, tesofensine has been shown to produce a placebo-subtracted weight loss of approximately 4% for >14 weeks without any diet and lifestyle therapy, which is similar to that of sibutramine, but with no effect on blood pressure 5.
Dosage and Administration
The optimal dosage of tesofensine for the treatment of obesity and Alzheimer's disease is still being investigated.
- Studies have used dosages ranging from 0.25 to 1.0 mg per day, with the 0.5 mg dose showing the most promising results 2, 3.
- Tesofensine has been administered orally once daily, and its efficacy and safety have been evaluated in phase II clinical trials 6.
Safety and Efficacy
The safety and efficacy of tesofensine have been evaluated in several clinical trials.
- The most common adverse events caused by tesofensine were dry mouth, nausea, constipation, hard stools, diarrhea, and insomnia 3.
- Tesofensine has been found to cause dose-dependent elevations in heart rate, with significant increases in blood pressure at the highest dose tested 6.
- Overall, tesofensine has been associated with minor adverse events and has been found to be well-tolerated in clinical trials 6.