Research Studies/Clinical Trials

Optimal dopamine levels have a positive impact on appetite regulation, metabolism, and motivation. On the other hand, dopamine deficiency can promote weight gain. Dopamine suppresses appetite, reduces cravings, and lowers calorie consumption. It also boosts metabolism by increasing thermogenesis, leading to improved calorie burning and increased energy expenditure. Moreover, dopamine enhances motivation and satisfaction, which helps produce feelings of satiety.

Tesofensine is widely known as a weight loss drug. Researchers believe that tesofensine may help treat obese and overweight patients because it boosts the levels of dopamine in the brain. A deficiency in this neurotransmitter has been shown to be linked with overeating and obesity. [1-5]

Fat oxidation, also known as lipid oxidation or fat burning, refers to the process by which stored fat is broken down and converted into usable energy within the body. There are some mechanisms by which tesotensine may contribute to increased fat burning such as increased metabolism, appetite suppression, and modulation of neurotransmitters. As an appetite suppressant, it may indirectly promote increased physical activity which leads to increased fat oxidation. When combined with lifestyle modification, the body responds well to the effects of tesofensine.

Clinical trials involving tesofensine have evaluated its efficacy and safety in promoting weight loss:

1. The results of phase Ill trials such as the 2018 phase 3 Viking study showed that obese participants who received both doses of oral tesofensine (0.25 and 0.50 mg once daily) had statistically and clinically significant reductions in weight with low incidence of adverse events at week 24. [6]
2. The results of clinical trials such as the Phase Il b trial (TIPO-1) showed that obese patients lost an average of

12.8 kg on the 1 mg dose, 11.3 kg on the 0.5 mg dose, and 6.7 kg on the 0.25 mg dose of tesofensine (dose-dependent increase), and showed no statistically significant increases in systolic or diastolic blood pressure, compared with a 2.2 kg loss in the placebo group. [7] The 24-hour fat oxidation (fat burning) also increased by 15% and there was a reduction in protein oxidation (the breakdown of protein due to the presence of reactive oxygen species)

1. In the TIPO-2 trial, tesofensine administration in obese individuals reduced their desire to eat and increased their satiety levels after 14 days of treatment. [8]
2. In patients with obesity, tesofensine treatment at varying doses (0.25 mg, 0.5 mg, or 1.0 mg) resulted in statistically significant and clinically relevant weight reductions with positive effects on energy balance and appetite. The patients were also able to increase their physical activity gradually, which led to improved quality of life. Significant results were seen in the highest dose groups. [9]
3. In obese participants, tesofensine administration at a dose of 0.5 mg for 26 weeks produced weight reductions twice that of anti-obesity agents such as sibutramine or rimonabant. [10]
4. In overweight patients, tesofensine administration for 24 weeks is associated with enhanced appetite suppression and significant weight reductions. [11]
5. In phase Il clinical trials with tesofensine in obese individuals, significant reductions in weight, body fat, and waist circumference were observed without any adverse side effects. [12]
6. In obese individuals, long-term tesofensine supplementation was well-tolerated and resulted in statistically significant and clinically relevant weight loss. [13]
7. In patients with Parkinson’s or Alzheimer’s disease, tesofensine administration once daily for 14 weeks induced weight loss of approximately 4%, which is similar to that of sibutramine. [14]
8. In healthy males, multiple administrations of tesofensine at doses of 0.125-1 mg resulted in the following positive results: increased dopamine levels and appetite suppression. [15]
9. In diet-induced obese rats, tesofensine administration resulted in appetite suppression and weight loss with a reversal of low forebrain dopamine levels. [16-17]
10. In a rat model of diet-induced obesity (DIO), administration of tesofensine (2.0 mg/kg, s.c.) for 16 days significantly reduced body weights. [18]
11. In diet-induced obese rats, tesofensine treatment at 2 mg/kg for 28 days decreased food consumption and produced dramatic weight losses while preventing weight gain. [19]
12. In 203 obese persons, tesofensine 0.5 mg produced a weight loss twice that of currently approved anti-obesity medications. [20]
13. In obese participants, tesofensine administration resulted in a 10% average weight loss in 24 weeks. The patients were also able to increase their physical activity gradually after the treatment. [21]
14. A study showed that tesofensine showed a more significant effect on body weight than that of currently approved anti-obesity drugs. |22
15. In obese patients, tesofensine in combination with an energy-restricted diet effectively reduced the weight of the subjects. |23]