some studies show that in western countries more than 80% of individuals with type 2 diabetes also suffer from obesity . other life threatening risks related to obesity are hypertension , dyslipidemia , coronary artery disease , cerebral vascular accident ( cva ) and gall bladder disorders . it is recommended that moderate weight loss in obese diabetic patients can lower serum glucose and lessen the amount of insulin needed . 5 - 10% weight loss in obese patients can reduce blood pressure in all individuals and can lessen the need for hypertension drugs in mild to moderate hypertensive patients . although a life style change consisting of physical activity and dietary regime is the basic way to control and treat obesity , the result is often disappointing . pharmacotherapy is usually reserved for patients with a bmi greater than 30 kg / m without complications or a bmi greater than 27 to 30 kg / m with concomitant weight - related complications . pharmacotherapy is typically initiated if the patient has been unsuccessful in attaining their weight loss target after 6 months of lifestyle modification , but it must be used in conjunction with a program that includes dietary changes and physical activity . therefore , there is a demand for new weight reducing drugs to help diabetic patients lose weight . topiramate , discovered in 1979 by bruce e. maryanoff and joseph f. gardoki , first prescribed as an anticonvulsant drug . this drug can block voltage mediated sodium gates in the central nervous system and prevents repeated stimulation of neurons with an 80% oral bioavailability and a 20 - 30 h half life , most of the topiramate consumed is excreted by the body , unchanged in the urine . this drug has also been investigated for use to treat alcoholism , post - traumatic stress disorder ( ptsd ) , periventricular leukomalacia and binge eating disorder there have been several studies showing the weight reducing effect of topiramate . the studies on humans demonstrated that amounts of weight loss from topiramate were related to the dose and duration of administration . however , there is a need for more accurate and precise research on its effect on different ethnic groups and medical conditions . the determination of an effective weight reducing medication would be helpful to combat the high prevalence of obesity and its complications . topiramate offers an effective possibility , but research is needed to gain information with a more global perspective . the aim of this study was to evaluate the effect of topiramate on weight loss in iranian patients with type 2 diabetes . the subjects for this randomized , double - blind , placebo - controlled , parallel group study were recruited from the institute of endocrinology and metabolism , firouzgar hospital , tehran , iran . the trial was from october 2008 to february 2010 ( rct code : irct201112036027n2 ) and was planned for 32 weeks , consisting of a 1-week run - off placebo phase , a 3-week titration phase , a 26-week maintenance phase , and a 2-week taper phase ( see flow chart ) . consort flow diagram for the effect of topiramate on weight loss in iranian patients with type two 2 diabetes the sampling was made by stratified randomization ( by age and gender ) on patients who fulfilled our inclusion criteria . all individuals were referred to a single endocrinologist ( blinded to drug administration ) and the study was fully introduced to the participants ( also blinded to drug administration ) . both topiramate and placebo were similar in size , shape and color and administered randomly by a pharmacist in the hospital which the study was taken place and the results were stored by their insurance code . the sample size was calculated at least 30 individuals in each group by  estimation of mean difference between two groups  formula according to of rosenstock et al . study on base of bmi changes (  = 0.05 ,  = 0.8 , 1 = 0.8  1.1 and 2 = 2.1  1.8 ) . in our study , 85 individuals were included ; however after starting the protocol , only 69 patients ( 21 male and 48 female ) were assessed as intention to treat ( itt ) population . the criteria for participation in the study were considered as followed : age 18 - 75 years ; body mass index ( bmi ) between 27 and 50 kg / m ; a documented history of type 2 diabetes mellitus ; glycosylated hemoglobin ( hba1c ) less than 11% ; fasting plasma glucose between 126 and 240 mg / dl ; blood pressure ( bp ) less than 160/105 mmhg and a constant weight for at least 3 months ( 3 kg ) . the dose of hyper - lipidemic medication that had been stable for at least 3 months ( the dose was to be maintained for the duration of the study ) . female subjects of childbearing age were required to use an approved method of birth control . subjects with a history of central nervous system ( cns ) related or psychiatric disorders , significant renal , hepatic , and thyroid diseases were excluded from the study any time after participation . all subjects participated in a non - pharmacologic lifestyle intervention program , designed and performed by the nutrition counselors of the institute during the study . the emphasis of the program was a diet composed of low - salt ( 1,500 mg / day ) with a maximum of 30% fat and an energy content that was 300 kcal less than the patient 's daily energy . the goal population was stratified into different life - style and medication , then the samples were randomly selected split into two groups ; one to receive the placebo and the other topiramate at a doses of 150 mg / day , 100 mg each morning and 50 mg every evening . the 3-week titration phase began with administration of 25 mg topiramate once every morning to subjects assigned to that group . in the second week , topiramate was administered at 25 mg twice daily ( 50 mg / day ) . the dose was thereafter increased to 100 mg / day ( 50 mg in the morning and 50 mg in the evening ) . the maintenance phase begun in the 4 week with the dose of 150 mg / day . during the maintenance phase , the dose remained constant ( placebo and 150 mg / day , divided in to twice daily doses as stated above ) . finally the dose was tapered to75 mg / day in the first week and 25 mg / day in the second week up to either completion of or early withdrawal from the study . a follow - up evaluation was performed 2 weeks after the treatment was stopped . before including any individual in our study , all subjects signed a consent form stating that they willing to participate in our study . all subjects could exit the trial whenever they want and no charges were defined for the participant . none of the information will be released individually and all participants were included as anonymous . our study was approved by ethics committee of hemmat campus of tehran university of medical sciences ( formerly : iran university of medial sciences ) before initiating the research ( ethics code 501 , date of approval : august 20 , 2008 ) the primary efficacy end point was the percent change in bmi at the end of the study . the secondary end points were changes in sitting systolic and diastolic bp ; the proportion of subjects who achieved 5% or 10% weight loss ( 5% and 10% weight responders ) ; the proportion of subjects who achieved a decrease of 5 or 10 mmhg in diastolic bp ( 5 and 10 mmhg diastolic bp responders ) or systolic bp ( 5 and 10 mmhg systolic bp responders ) ; changes in lipid profile ( total cholesterol , low - density lipoprotein cholesterol , high - density lipoprotein cholesterol , triglycerides ) ; and changes in glycosylated hemoglobin ( hga1c ) . however , all patients had been warned about the drugs side effects ( parasthesia , lack of concentration , pruritus , insomnia and dizziness ) and been advised to inform the endocrinologist . the participants would be excluded from the study if desired or the side effects was disabling . weight , height and blood pressure measurements for each patient were taken according to the appropriate scales ( richter inc . , all the biochemical assays were carried out at the institute of endocrine and metabolism laboratory ( firoozgar hospital , tehran , iran ) . total cholesterol , hdl and triglycerides were measured by photometric assay with intra- and inter - assay coefficients of variation less than 2% ( pars azmoon company ; iran ) . , illinois , usa ) using statistical tests ; paired samples t - test ( for within group analyses ) , independent samples t - test ( for between groups analysis ) and chi - square fisher exact test . efficacy data were assessed in the intent - to - treat ( itt ) population , defined as all subjects who were randomized , received at least one dose of study medication , and completed at least one efficacy measurement while on the treatment . the subjects for this randomized , double - blind , placebo - controlled , parallel group study were recruited from the institute of endocrinology and metabolism , firouzgar hospital , tehran , iran . the trial was from october 2008 to february 2010 ( rct code : irct201112036027n2 ) and was planned for 32 weeks , consisting of a 1-week run - off placebo phase , a 3-week titration phase , a 26-week maintenance phase , and a 2-week taper phase ( see flow chart ) . consort flow diagram for the effect of topiramate on weight loss in iranian patients with type two 2 diabetes the sampling was made by stratified randomization ( by age and gender ) on patients who fulfilled our inclusion criteria . all individuals were referred to a single endocrinologist ( blinded to drug administration ) and the study was fully introduced to the participants ( also blinded to drug administration ) . both topiramate and placebo were similar in size , shape and color and administered randomly by a pharmacist in the hospital which the study was taken place and the results were stored by their insurance code . the sample size was calculated at least 30 individuals in each group by  estimation of mean difference between two groups  formula according to of rosenstock et al . study on base of bmi changes (  = 0.05 ,  = 0.8 , 1 = 0.8  1.1 and 2 = 2.1  1.8 ) . in our study , 85 individuals were included ; however after starting the protocol , only 69 patients ( 21 male and 48 female ) were assessed as intention to treat ( itt ) population . the criteria for participation in the study were considered as followed : age 18 - 75 years ; body mass index ( bmi ) between 27 and 50 kg / m ; a documented history of type 2 diabetes mellitus ; glycosylated hemoglobin ( hba1c ) less than 11% ; fasting plasma glucose between 126 and 240 mg / dl ; blood pressure ( bp ) less than 160/105 mmhg and a constant weight for at least 3 months ( 3 kg ) . the dose of hyper - lipidemic medication that had been stable for at least 3 months ( the dose was to be maintained for the duration of the study ) . female subjects of childbearing age were required to use an approved method of birth control . subjects with a history of central nervous system ( cns ) related or psychiatric disorders , significant renal , hepatic , and thyroid diseases were excluded from the study any time after participation . all subjects participated in a non - pharmacologic lifestyle intervention program , designed and performed by the nutrition counselors of the institute during the study . the emphasis of the program was a diet composed of low - salt ( 1,500 mg / day ) with a maximum of 30% fat and an energy content that was 300 kcal less than the patient 's daily energy . the goal population was stratified into different life - style and medication , then the samples were randomly selected split into two groups ; one to receive the placebo and the other topiramate at a doses of 150 mg / day , 100 mg each morning and 50 mg every evening . the 3-week titration phase began with administration of 25 mg topiramate once every morning to subjects assigned to that group . in the second week , topiramate was administered at 25 mg twice daily ( 50 mg / day ) . the dose was thereafter increased to 100 mg / day ( 50 mg in the morning and 50 mg in the evening ) . the maintenance phase begun in the 4 week with the dose of 150 mg / day . during the maintenance phase , the dose remained constant ( placebo and 150 mg / day , divided in to twice daily doses as stated above ) . finally the dose was tapered to75 mg / day in the first week and 25 mg / day in the second week up to either completion of or early withdrawal from the study . before including any individual in our study , all subjects signed a consent form stating that they willing to participate in our study . all subjects could exit the trial whenever they want and no charges were defined for the participant . none of the information will be released individually and all participants were included as anonymous . our study was approved by ethics committee of hemmat campus of tehran university of medical sciences ( formerly : iran university of medial sciences ) before initiating the research ( ethics code 501 , date of approval : august 20 , 2008 ) the primary efficacy end point was the percent change in bmi at the end of the study . the secondary end points were changes in sitting systolic and diastolic bp ; the proportion of subjects who achieved 5% or 10% weight loss ( 5% and 10% weight responders ) ; the proportion of subjects who achieved a decrease of 5 or 10 mmhg in diastolic bp ( 5 and 10 mmhg diastolic bp responders ) or systolic bp ( 5 and 10 mmhg systolic bp responders ) ; changes in lipid profile ( total cholesterol , low - density lipoprotein cholesterol , high - density lipoprotein cholesterol , triglycerides ) ; and changes in glycosylated hemoglobin ( hga1c ) . however , all patients had been warned about the drugs side effects ( parasthesia , lack of concentration , pruritus , insomnia and dizziness ) and been advised to inform the endocrinologist . the participants would be excluded from the study if desired or the side effects was disabling . weight , height and blood pressure measurements for each patient were taken according to the appropriate scales ( richter inc . all the biochemical assays were carried out at the institute of endocrine and metabolism laboratory ( firoozgar hospital , tehran , iran ) . total cholesterol , hdl and triglycerides were measured by photometric assay with intra- and inter - assay coefficients of variation less than 2% ( pars azmoon company ; iran ) . all data were analyzed by spss for windows version 16 ( spss inc . , illinois , usa ) using statistical tests ; paired samples t - test ( for within group analyses ) , independent samples t - test ( for between groups analysis ) and chi - square fisher exact test . efficacy data were assessed in the intent - to - treat ( itt ) population , defined as all subjects who were randomized , received at least one dose of study medication , and completed at least one efficacy measurement while on the treatment . at the end of the study , 69 patients ( 21 male and 48 female ) were assessed as intention to treat ( itt ) population ; 39 in the topiramate group and 30 in the placebo group . the mean age was 52.45  8.57 years an d the mean weight at the time of the trial was 82.59  13.40 kg . as seen in table 1 , mean weight and mean bmi reduced significantly in the topiramate group after treatment . furthermore , mean weight of topiramate group was significantly lower than the placebo group after treatment . weight and bmi in itt subjects , a comparison between drug and placebo groups ; bolded p values are significant further analysis showed that the mean  weight ( calculated from  w= weight after treatment  weight before treatment ) was not significantly different between placebo and topiramate groups ( 5.18  0.99 vs. 1.83  0.50 kg , p = 0.523 ) . mean weight loss percentage ( w / weight before treatment ) was also without significant difference ( 5.55  1.06% vs. 3.40  0.61% , p = 0.492 ) . bmi ( calculated from : bmi = bmi before treatment  bmi after treatment ) was significantly higher in patients treated with topiramate ( -1.08  1.90 vs. + 0.086  1.05 kg / m , p = 0 . also mean bmi loss percentage ( calculated from : ( bmi / bmi before treatment ) 100 ) was significantly different between the active and placebo groups ( -3.02  5.78% vs. + 0.32  3.54% , p = 0.005 ) ; more information demonstrated in figures 1 and 2 . proportion of patients achieving 0 - 5% , 5 - 10% and more than 10% weight loss by topiramate and placebo box - plot of bmi reduction in topiramate and placebo groups ; as stated , they have significant difference systolic and diastolic blood pressure and hemoglobin a1c ( hga1c ) levels were evaluated in all patients . systolic blood pressure and hga1c significantly decreased in patients treated with topiramate ( p = 0.021 and p = 0.047 , respectively ) . total cholesterol in the placebo group significantly decreased in the topiramate group after treatment ( p = 0.048 ) . other data are classified in tables 2 and 3 which demonstrates no significant difference in other parameters . blood pressure and hemoglobin a1c in itt subjects , a comparison between drug and placebo groups ; bolded p values are significant lipid profile in itt subjects , a comparison between drug and placebo groups twenty - four patients in the topiramate group and nine cases in the placebo group had reported adverse effects . the most common of the side effects was paresthesia ( 12 cases in topiramate group and 3 in placebo group ; p = 0.041 ) and followed by difficulty with concentration ( 8 in topiramate group and 2 in placebo group ; p = 304 ) . other adverse effects were included pruritus , insomnia and dizziness ( less than 2 cases ) . at the end of the study , 69 patients ( 21 male and 48 female ) were assessed as intention to treat ( itt ) population ; 39 in the topiramate group and 30 in the placebo group . the mean age was 52.45  8.57 years an d the mean weight at the time of the trial was 82.59  13.40 kg . as seen in table 1 , mean weight and mean bmi reduced significantly in the topiramate group after treatment . furthermore , mean weight of topiramate group was significantly lower than the placebo group after treatment . weight and bmi in itt subjects , a comparison between drug and placebo groups ; bolded p values are significant further analysis showed that the mean  weight ( calculated from  w= weight after treatment  weight before treatment ) was not significantly different between placebo and topiramate groups ( 5.18  0.99 vs. 1.83  0.50 kg , p = 0.523 ) . mean weight loss percentage ( w / weight before treatment ) was also without significant difference ( 5.55  1.06% vs. 3.40  0.61% , p = 0.492 ) . bmi ( calculated from : bmi = bmi before treatment  bmi after treatment ) was significantly higher in patients treated with topiramate ( -1.08  1.90 vs. + 0.086  1.05 kg / m , p = 0 . also mean bmi loss percentage ( calculated from : ( bmi / bmi before treatment ) 100 ) was significantly different between the active and placebo groups ( -3.02  5.78% vs. + 0.32  3.54% , p = 0.005 ) ; more information demonstrated in figures 1 and 2 . proportion of patients achieving 0 - 5% , 5 - 10% and more than 10% weight loss by topiramate and placebo box - plot of bmi reduction in topiramate and placebo groups ; as stated , they have significant difference systolic and diastolic blood pressure and hemoglobin a1c ( hga1c ) levels were evaluated in all patients . systolic blood pressure and hga1c significantly decreased in patients treated with topiramate ( p = 0.021 and p = 0.047 , respectively ) . total cholesterol in the placebo group significantly decreased in the topiramate group after treatment ( p = 0.048 ) . other data are classified in tables 2 and 3 which demonstrates no significant difference in other parameters . blood pressure and hemoglobin a1c in itt subjects , a comparison between drug and placebo groups ; bolded p values are significant lipid profile in itt subjects , a comparison between drug and placebo groups twenty - four patients in the topiramate group and nine cases in the placebo group had reported adverse effects . the most common of the side effects was paresthesia ( 12 cases in topiramate group and 3 in placebo group ; p = 0.041 ) and followed by difficulty with concentration ( 8 in topiramate group and 2 in placebo group ; p = 304 ) . other adverse effects were included pruritus , insomnia and dizziness ( less than 2 cases ) . statistically , significant weight loss was achieved in obese type 2 diabetic subjects treated with topiramate in this study . , it has been demonstrated that a modest reduction in body weight will considerably improve glycemic control in subjects with type 2 diabetes . in our study , weight changes from baseline ( > 5% ) were seen in 25% of subjects in the topiramate group compared with the placebo group ( < 5% of cases ) . this may account for improvement in hba1c . although the effect of topiramate on systolic blood pressure and cholesterol were statistically significant , triglyceride changes , that can be more dependent on body weight , did not differ significantly . in the current study , the effect of topiramate was less compared with other studies that had used higher doses of topiramate for longer durations . some studies suggest that topiramate can be more effective with longer treatment ; hence , in subjects who did not show any persistent or adverse side effects , it could be used for longer periods . in a study conducted by wilding et al . , the mean decrease in body weight with topiramate 192 mg / day was 9.1% and 61% of these subjects lost at least 5% of their baseline body weight at week 60 of the treatment . hence , there were no statistically significant differences in weight loss between the groups treated with doses of 256 and 192 mg / day . additional weight loss was observed in this study compared with our study ; the difference could be attributed to the longer treatment duration , but the results are comparable at month 6 ( near 5.5% weight loss ) . in another randomized placebo - controlled study , a total of 111 subjects were studied for 16 weeks , which demonstrated ( 2.5 vs. 6 kg , p < 0.001 ) weight loss and 0.4% vs. 0.7% lowering effect in hga1c , concluding improvements in diabetic patients , however , the authors did not recommend it due to central nervous system and psychiatric adverse events . recently , combination of topiramate with phentermine has been evaluated in two big studies for weight loss which demonstrated near 10% weight loss and 0.3 - 0.7% reduction in hga1c . even more significantly , eliasson et al . demonstrated a 6.6% weight loss with 9 months topiramate treatment in obese subjects with type 2 diabetes . the mechanisms underlying the effect of topiramate on lowering hba1c and fbs of diabetic patients are not clear yet . several studies have demonstrated whole - body insulin sensitivity following topiramate treatment although this would have been expected considering the over - all effect on glucose control . however , a similar discrepancy between insulin - stimulated glucose uptake during a clamp and fasting glucose levels has also recently been shown in dm2 patients following 3% reduction in body weight the most common adverse responses to topiramate were paresthesia and amnesia : side effects that were realized early on in the study . most of the patients stated that these effects are not much a problem and tried to comply with the study . the main limitations of this study were its short duration and the small sample size due to the non - co - operation state of some subjects . we recommend more studies with narrower inclusion criteria and larger sample size with different conditions with a long duration of follow - up in iran and other middle to low income counties . treatment of obese diabetic patients with 150 mg / day topiramate can be suitable for near 5% weight loss . topiramate may be effective in improving metabolic parameters associated with obesity and glycemic control in diabetes type two patients .
background : obesity has been associated with several co - morbidities such as diabetes and increased mortality . in general 
 , the use of medication promotes only a modest weight loss in the range of 2 to 10 kg , usually most effective during the first 6 months of therapy ; however , studies have shown positive effects on other risk factors such as blood pressure and serum glucose levels , but there are fewer studies in patients with diabetes . 
 the aim of this study was to assess the effect of topiramate on weight reduction patients with type 2 diabetes.materials and methods : this was a 32-week randomized clinical trial study of 69 subjects during 2008 - 2010 . 
 patients , in two treatment groups were given topiramate ( 39 patients ) and placebo ( 30 patients ) and were subjected to participation in a non - pharmacologic lifestyle intervention program ; which were randomly allocated in our two groups . the percentage change in body weight and body mass index ( bmi ) at the end of the study was the primary efficacy endpoint and secondary indicators were changes in blood pressure ( bp ) , proportion of subjects who achieved 5% or 10% weight loss , changes in lipid profile ( total cholesterol , low - density lipoprotein cholesterol , high - density lipoprotein cholesterol , triglycerides ) ; and changes in glycosylated hemoglobin ( hga1c ) . paired samples and independent samples t - test was used for statistical analysis . 
 ( rct code : irct201112036027n2).results : all results were extracted on base of 69 ( intended to treat ) itt patients . 
 mean bmi changes was significantly higher in patients treated with topiramate ( -1.08 1.90 vs. + 0.086  1.05 kg / m , p = 0.006 ) . 
 mean weight loss percentage was significantly different between active and placebo groups ( -3.02  5.78% vs. + 0.32  3.54% , p = 0.005 ) and systolic blood pressure and hga1c significantly decreased in patients treated with topiramate ( p = 0.021 and p = 0.047 , respectively).conclusion : topiramate induced weight loss and improved glycemic control in obese , diabetic patients .