topiramate and Diabetes-Mellitus

Obesity is a serious chronic disease. Controlled-release phentermine/topiramate (PHEN/TPM CR), as an adjunct to lifestyle modification, has previously shown significant weight loss compared with placebo in a 56-wk study in overweight and obese subjects with ≥2 weight-related comorbidities.. This study evaluated the long-term efficacy and safety of PHEN/TPM CR in overweight and obese subjects with cardiometabolic disease.. This was a placebo-controlled, double-blind, 52-wk extension study; volunteers at selected sites continued with original randomly assigned treatment [placebo, 7.5 mg phentermine/46 mg controlled-release topiramate (7.5/46), or 15 mg phentermine/92 mg controlled-release topiramate (15/92)] to complete a total of 108 wk. All subjects participated in a lifestyle-modification program.. Of 866 eligible subjects, 676 (78%) elected to continue in the extension. Overall, 84.0% of subjects completed the study, with similar completion rates between treatment groups. At week 108, PHEN/TPM CR was associated with significant, sustained weight loss (intent-to-treat with last observation carried forward; P < 0.0001 compared with placebo); least-squares mean percentage changes from baseline in body weight were -1.8%, -9.3%, and -10.5% for placebo, 7.5/46, and 15/92, respectively. Significantly more PHEN/TPM CR-treated subjects at each dose achieved ≥5%, ≥10%, ≥15%, and ≥20% weight loss compared with placebo (P < 0.001). PHEN/TPM CR improved cardiovascular and metabolic variables and decreased rates of incident diabetes in comparison with placebo. PHEN/TPM CR was well tolerated over 108 wk, with reduced rates of adverse events occurring between weeks 56 and 108 compared with rates between weeks 0 and 56.. PHEN/TPM CR in conjunction with lifestyle modification may provide a well-tolerated and effective option for the sustained treatment of obesity complicated by cardiometabolic disease. This trial was registered at clinicaltrials.gov as NCT00796367.

Topics: Adult; Anti-Obesity Agents; Cardiovascular Diseases; Delayed-Action Preparations; Diabetes Mellitus; Double-Blind Method; Drug Combinations; Female; Fructose; Humans; Incidence; Intention to Treat Analysis; Least-Squares Analysis; Male; Metabolic Diseases; Middle Aged; Obesity; Overweight; Patient Dropouts; Phentermine; Time; Topiramate; Weight Loss

The current study aimed to test the neuroprotective action of topiramate in mouse peripheral diabetic neuropathy (DN) and explored some mechanisms underlying this action. Mice were assigned as vehicle group, DN group, DN + topiramate 10-mg/kg and DN + topiramate 30-mg/kg. Mice were tested for allodynia and hyperalgesia and then spinal cord and sciatic nerves specimens were examined microscopically and neurofilament heavy chain (NEFH) immunostaining was performed. Results indicated that DN mice had lower the hotplate latency time (0.46-fold of latency to licking) and lower von-Frey test pain threshold (0.6-fold of filament size) while treatment with topiramate increased these values significantly. Sciatic nerves from DN control mice showed axonal degeneration while spinal cords showed elevated GFAP (5.6-fold) and inflammatory cytokines (∼3- to 4-fold) but lower plasticity as indicated by GAP-43 (0.25-fold). Topiramate produced neuroprotection and suppressed spinal cord GFAP/inflammation but enhanced GAP-43. This study reinforces topiramate as neuroprotection and explained some mechanisms included in alleviating neuropathy.

Topics: Animals; Diabetes Mellitus; Diabetic Neuropathies; Disease Models, Animal; GAP-43 Protein; Hyperalgesia; Intermediate Filaments; Mice; Neuroprotection; Topiramate

There is still limited knowledge regarding the role of impaired brain glucose metabolism in the generation of aggression during diabetes. Additionally, there are rapidly replicating piece of evidence suggesting that topiramate may exert significant mood stabilizing effect. In this respect, we aimed to evaluate the neurometabolic correlates of the therapeutic effect of topiramate in a patient with diabetes and Intermittent explosive disorder (IED).. We measured regional cerebral glucose metabolism using 2-[18F]-fluoro-2-deoxy-D-glucose and positron emission tomography (FDG-PET) in a diabetic patient with aggressive outbursts before and after treatment with topiramate. In order to reveal a defined information underlying the improvement of the aggressive symptoms we also combined the PET with Modified Overt Aggression Scale.. We have found that topiramate leads to the improvement in Modified Overt Aggression Scale that was well correlated with the increase in cortical brain metabolism.. The therapeutic role of topiramate may not only suggest secondary deficits due to diminished functions of the cortical part of emotional circuits but also indicate that diabetic individuals may be vulnerable to lower cerebral glucose metabolism in cortical regions. Further clinical trials that include well-conducted randomized controlled trials and cohort studies by using other methods (i.e., magnetic resonance spectroscopy and quantitative EEG analysis) are necessary to confirm our preliminary findings.

Topics: Adult; Aggression; Animals; Brain; Diabetes Mellitus; Fructose; Humans; Male; Positron-Emission Tomography; Topiramate

To study topiramate's new functions according to the medicinal property combinations, in order to apply the traditional Chinese medicinal theory in discovering new purposes of old drugs.. According to New Traditional Chinese Medicinal Families--Chemical Traditional Chinese Medicines, the authors found out topiramate's property. Then based on the therapeutic principle of diabetes, hypertension, epilepsy and lung cancer, as well as the relations of efficacies and medicinal property combinations, they summarized the corresponding medicinal property combination modes, compared topiramate's medicinal property combination mode with corresponding medicinal property combination modes of these diseases, and predict topiramate's new functions.. According to the comparison, the corresponding medicinal property combinations were consistent with topiramate's medicinal property combinations as evidenced by corresponding literatures, whereas other medicinal property combinations were not.. Based on medicinal property combination modes, the authors screened topiramate's new functions according to e of TCM clinical experience, discovered topiramate's therapeutic effects on diabetes, hypertension and lung cancer in addition to epilepsy, and explore new drug function according to medicinal property combination modes, which could help greatly shorten the new drug R&D period.

Topics: Diabetes Mellitus; Drug Therapy, Combination; Drugs, Chinese Herbal; Fructose; Humans; Hypertension; Lung Neoplasms; Phytotherapy; Topiramate

Topics: Administration, Oral; Amyloid; Diabetes Mellitus; Diabetic Neuropathies; Drug Combinations; Drug Delivery Systems; Fructose; Humans; Hypoglycemic Agents; Indoles; Insulin; Insulin Lispro; Islet Amyloid Polypeptide; Maleimides; Neuroprotective Agents; Topiramate