Combination of Topiramate and Empagliflozin is Considered a Good Option for the Treatment of Obesity

Introduction: The incidence of obesity has risen very much in the latest decades in which more than 30% of peoples are considered obese [1]. It is evidenced that genetics has a great impact on obesity occurrence; all in all, the risk of getting obesity in the future is linked to many factors like sedentary lifestyle, type of diet [4]. Aside from decreasing blood glucose, empagliflozin can lead to a reduction of weight due to the loss of calories by excretion of glucose [17]. Research papers also discuss the weight reducing effect of topiramate and demonstrated that this effect is dependent on the dose of the drug and duration of treatment [24].Objectives: The aim was to show if combination of topiramate and empagliflozine have the greatest weight decreasing effect in comparison to each drug alone and to placebo. Design: Randomised, placebo controlled trial, 6 month trial. Materials and Methods: 200 obese patients were randomized into 4 parallel groups. 4 groups of patients with obesity had been monitored in a private clinic, each group 50 patient’s number, with 35 females and 15 males after written consent from all patients. Result: The results show that both topiramate and empagliflozine have weight loss effect if used alone with significant p value which is 0.0480 with topiramate and 0.0048 in empagliflozine and the greatest weight loss effect if used in combination with p value less than 0.0001. Conclusion: Combination of topiramate and empagliflozin show a considerable reduction of body weight and so is considered as an option for treatment of obesity.


INTRODUCTION
The incidence of obesity has risen very much in the latest decades in which more than 30% of peoples are considered obese [1].
Obesity is defined as exaggerated fat that is deposited abnormally in tissues and make health hazards, promoting adipose tissue dysfunction. Guidelines state that the normal body mass index is from 18.5 to 24.9, BMI from =25kg/m2 to 29.9 kg/m2 is known to be overweight, BMI=30kg/m2 known to be obese. The body mass index (BMI) is a value extracted from (weight) and height of a person [2].
Obesity is considered a disease that is generated from many factors affecting energy balance, as input is more than the output, which is transformed into triglycerides making fat cells larger in size causing an increase in weight [3]. It is evidenced that genetics has a great impact on obesity occurrence; all in all, the risk of getting obesity in the future is linked to many factors like sedentary lifestyle, type of diet [4]. One of the most important factors determining obesity risk is genetics . Aside from decreasing blood glucose, empagliflozin can lead to a reduction of weight due to the loss of calories by excretion of glucose [17]. Empagliflozin inhibit urinary glucose reabsorption, in which 10 mg of empagliflozin can prevent absorption of about 40% of glucose increasing with dose to 90 g of glucose.
With the use of empagliflozin in nondiabetic persons, no decrease in blood glucose level, because of the liver increase glucose production [15].
Empagliflozin is a well-tolerated drug but with an inconsiderable occurrence of genital infections, and no increase in frequency in urinary tract infections [18]. Topiramate is a drug used for the treatment of convulsions and migraine. Topiramate is known to decrease appetite and so used off-label for obesity [19]. Topiramate is used for migraine by a dose of 100 mg and Journal of Clinical/Pharmaco-Epidemiology Research Volume 1 Issue 2 by a dose up to 400 mg for epilepsy and in combination with pheniramine for obesity by a dose from 23 to 90 mg [20].
Topiramate is a drug that is detected in 1979 as an anticonvulsant with t half of about 30 hours and leads to debates and disputes and is used for the treatment of obesity [21]. There are many types of research discussing the role of topiramate in the treatment of many diseases like binge eating disorder [22] and posttraumatic stress disorder [23]. Research papers also discuss the weight reducing effect of topiramate and demonstrated that this effect is dependent on the dose of the drug and duration of treatment [24].
Topiramate is a drug that is known to have anti-impulsive behaviour effect [25]. In one study topiramate given to mouses led to a decrease in body fat and decreased food intake with the increasing metabolic rate [26]. With decreasing lipoprotein lipase activity [27], and in a clinical trial in patients with epilepsy taking topiramate, the patient's weights decrease in the early period of treatment with 2 to 5 % decrease in weight, weight loss increase by 18 months of treatment [28]. The first group patients received topiramate 25 mg twice daily for 6 months, the second group received empagliflozin 10 mg once daily, the third group patients received topiramate 25 mg twice daily and empagliflozin 10 mg once daily, the fourth group received placebo for 6 months. During the period of treatment, we followed the patients for weight loss and if there were side effects of the drugs used. No side effects were monitored during the period of treatment except for frequency of micturation in patients using empagliflozine.

RESULTS
Each group was compared with the placebo group after 6 months of treatment. For analysis of data, the unpaired T-test was used.        The results show that both topiramate and empagliflozine have weight loss effect if used alone with significant p value which is 0.0480 with topiramate and 0.0048 with empagliflozine and the greatest weight loss effect is with combination with p value less than 0.0001.

DISCUSSION
There is a great risk of developing diseases and early mortality in patients with obesity, also obesity has a bad effect on the quality of life, by affecting mental and physical health [29]. Wide use of 'Western diet' with high energy all over the world explains the high prevalence of obesity worldwide, not only diet is the culprit also there is a great rule for genetic and epigenetic factors for the occurrence of weight gain [30].
The occurrence of obesity and changes in body weight could be caused by genetic factors, environmental factors or interaction between the 2 factors. Also, diet in pregnancy has a considerable effect Journal of Clinical/Pharmaco-Epidemiology Research Volume 1 Issue 2 on DNA methylation that impacts its effect for a long time and inherited by upcoming generations [31].
As obesity prevalence increases very much in the last years all over the world and increased health problems related to it, it is a must to develop new ways for the treatment of obesity [32].
Empagliflozin which is the most selective sglt2 inhibitor when compared with placebo leads to great bodyweight reduction with decreasing visceral fat in patients with obesity [33].
Topiramate is a drug which is approved for use in the treatment of epilepsy and migraine. It had a considerable effect on decreasing body weight by reducing calorie input and change in taste [34]. And by comparing topiramate with placebo, there were considerable improvement in blood pressure and in lipid profile with an increase in HDL and a decrease in triglyceride levels [35]. In my trial, combination of topiramate and empagliflozine results in considerable decrease in weight compared to each drug alone and compared to placebo. The restriction of my study is the few patients sample size. While the inclusion of a small number of patients limits and restricts the extrapolation of our findings to the general population, obesity is a serious health problem, and my study aims to find a new treatment option for obesity.
My findings in this study indicate that combination of topiramate and empagliflozine is a potential treatment for obesity by decreasing body weight, visceral obesity and improving lipid profile. Further large-scale studies and clinical trials are required to confirm our results.

CONFLICTS OF INTEREST
There is no conflict of interest to declare.

CONCLUSION
As obesity prevalence increases very much worldwide, there is an urgent need to discover a new treatment option for diabetes to control this epidemic. Now, there are many approved drugs for obesity, but maximal body weight reduction is about 5%.Combination of drugs is considered as an optimal option for the treatment of diabetes. Combination of topiramate and empagliflozin show a considerable reduction of body weight and so is considered as an option for treatment of obesity.