A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Assess the Efficacy and Safety of Topiramate Controlled Release in the Treatment of Obese Type 2 Diabetic Patients
ABSTRACT This is a randomized, placebo-controlled study of the weight-loss efficacy and safety of a controlled-release (CR) formulation of topiramate in overweight and obese patients with type 2 diabetes treated with diet and exercise alone or in combination with metformin.
Patients with type 2 diabetes, BMI > or =27 kg/m2, A1C >6.5 and <11.0%, treated with diet and exercise alone or in combination with metformin monotherapy were enrolled. Patients were randomized to placebo or topiramate CR titrated up to 175 mg/day. Treatment consisted of a 7-week titration phase followed by a 9-week maintenance phase.
A total of 111 subjects were randomized and analyzed. By the end of week 16, patients in the placebo and topiramate groups lost 2.5 and 6.0 kg, which represented 2.3 and 5.8%, respectively, of their baseline body weight (P < 0.001 vs. placebo). A1C improved from a baseline of 7.4% in the placebo and 7.6% in the topiramate groups to 7.1 and 6.7%, respectively, representing a 0.4 and 0.9% reduction from baseline, respectively (P < 0.001 vs. placebo). Topiramate also significantly reduced blood pressure and urinary albumin excretion. Adverse events were predominantly neuropsychiatric or central and peripheral nervous system related.
Topiramate CR treatment produced significant weight loss and meaningful improvements in A1C and blood pressure in obese patients with type 2 diabetes treated with diet and exercise or in combination with metformin. However, the central nervous system and psychiatric adverse event profile of topiramate CR makes it unsuitable for the treatment of obesity and diabetes.
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- "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% "
ABSTRACT: 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. 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). 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/m², 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). Topiramate induced weight loss and improved glycemic control in obese, diabetic patients.Journal of research in medical sciences 04/2013; 18(4):297-302. · 0.61 Impact Factor
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- "Although the overall incidence was not high, because subjects with a documented history of major depressive episodes or current depressive episode of moderate or higher severity were excluded, the question as to whether this medication is safe in patients with affective disorders remains unanswered. Also, considering recent reports of topiramate-related CNS adverse-effects,35) the depressive symptoms may have been caused by topiramate and not phentermine. "
ABSTRACT: A safe and effective way to control weight in patients with affective disorders is needed, and phentermine is a possible candidate. We performed a PubMed search of articles pertaining to phentermine, sibutramine, and affective disorders. We compared the studies of phentermine with those of sibutramine. The search yielded a small number of reports. Reports concerning phentermine and affective disorders reported that i) its potency in the central nervous system may be comparatively low, and ii) it may induce depression in some patients. We were unable to find more studies on the subject; thus, it is unclear presently whether phentermine use is safe in affective disorder patients. Reports regarding the association of sibutramine and affective disorders were slightly more abundant. A recent study that suggested that sibutramine may have deleterious effects in patients with a psychiatric history may provide a clue for future phentermine research. Three explanations are possible concerning the association between phentermine and affective disorders: i) phentermine, like sibutramine, may have a depression-inducing effect that affects a specific subgroup of patients, ii) phentermine may have a dose-dependent depression-inducing effect, or iii) phentermine may simply not be associated with depression. Large-scale studies with affective disorder patients focusing on these questions are needed to clarify this matter before investigation of its efficacy may be carried out and it can be used in patients with affective disorders.Clinical Psychopharmacology and Neuroscience 04/2013; 11(1):7-12. DOI:10.9758/cpn.2013.11.1.7
- Endocrine Practice 17(4):658-9. · 2.59 Impact Factor