Efficacy and safety of topiramate in combination with metformin in the treatment of obese subjects with type 2 diabetes: a randomized, double-blind, placebo-controlled study.
ABSTRACT To investigate the efficacy and safety of topiramate in obese subjects with type 2 diabetes treated with metformin.
This was a multicenter, double-blind, placebo-controlled trial. All subjects received a non-pharmacological program of diet, exercise and behavioral modification throughout the study; the assigned diet was 600 kcal/day less than the subject's individually calculated energy expenditure. After a 6-week single-blind placebo run-in, subjects were randomized to placebo, topiramate 96 mg/day or topiramate 192 mg/day. Following an 8-week titration period, subjects remained on their assigned dose for 52 weeks. However, the sponsor ended the study early in order to develop a new controlled-release formulation with the potential to enhance tolerability and simplify dosing in this patient population. A total of 646 obese men and women (age: 18-75 years, body mass index: 27-50 kg/m(2)) with an established history of type 2 diabetes mellitus controlled by metformin monotherapy were randomized. Efficacy was assessed in a pre-determined modified intent-to-treat (MITT) population of 307 subjects whose randomization date would have allowed them to complete 24 weeks on study medication before the announcement of study termination.
Joint primary efficacy parameters were mean percent change in weight and change in glycosylated hemoglobin (HbA(1c)) from baseline to week 24.
Subjects in the placebo, topiramate 96 mg/day and topiramate 192 mg/day groups lost 1.7%, 4.5% (P<0.001) and 6.5% (P<0.001), respectively, of their baseline body weight and had absolute decreases in HbA(1c) of 0.1%, 0.4% (P<0.001) and 0.6% (P<0.001) (MITT, last observation carried forward). Topiramate-treated subjects also experienced statistically significant decreases in systolic blood pressure. Most common adverse events were paresthesia and events related to the central nervous system.
Topiramate was effective for weight reduction and improvement in glycemic control in obese subjects with type 2 diabetes treated with metformin monotherapy. Further study in obese diabetics is warranted.
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ABSTRACT: Weight loss can reduce the increased cardiovascular risk associated with obesity. Pharmacotherapy is a recognized weight loss treatment option; however, cardiovascular safety issues with some previous weight loss drugs raise concerns for newly approved pharmacotherapies. Phentermine is approved for short-term obesity treatment in conjunction with lifestyle modifications, but is commonly used chronically. Topiramate, approved for treating epilepsy and preventing migraines, also induces weight loss. A single-dose combination of low-dose phentermine and topiramate extended-release was recently approved by the United States Food and Drug Administration as an adjunct to lifestyle intervention for the chronic treatment of overweight/obese adults. This review summarizes and evaluates the cardiovascular risk/benefit profile associated with phentermine and topiramate, individually and in combination. Cardiovascular data associated with long-term use of phentermine and topiramate extended-release indicate that this combination may be a safe and effective option for reducing weight in overweight/obese patients at low-to-intermediate cardiovascular risk.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivitives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/3.0.Journal of Hypertension 03/2014; 32(6). DOI:10.1097/HJH.0000000000000145 · 4.22 Impact Factor
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ABSTRACT: Objective: The aim of this systematic review was to examine randomized clinical trials (RCT) regarding long-term effects of weight loss (WL) on biological markers in people with type 2 diabetes mellitus (T2DM). Methods: We searched for articles published in English and Spanish recorded in the databases of Pubmed and Cochrane , and the journal collections platforms of Ebsco and Scielo between January 1, 2000 and January 1, 2010. Inclusion criteria included RCT with follow-up ≥ 12 months. Results: A total of 842 articles were identified, 95 of them contained information on the effect of WL on biological markers. Twenty studies fulfilled the inclusion criteria. WL percentage ranged from 0.8 to 20%. A reduction of A1C was observed in nine studies, blood glucose in seven, of total cholesterol and LDL in four, systolic and diastolic blood pressure in three, and the use of hypoglycemic drugs in four; an increase of HDL was observed in seven studies. Remission of T2DM was reported in only one study, which included surgical treatment. The quality of the studies ranged from very low to high; however, the study with the longest follow-up that did not involve surgical treatment, was 52 months. Conclusion: The evidence of the beneficial effect of WL on biological markers on long-term studies in people with T2DM is inconclusive. These results warrant longer and better designed studies.Nutricion hospitalaria: organo oficial de la Sociedad Espanola de Nutricion Parenteral y Enteral 12/2011; 26(6):1242-1249. · 1.25 Impact Factor
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ABSTRACT: Introduction: When used prudently and in combination with lifestyle modification, pharmacotherapy has an important role in the management of obesity. Areas covered: This review covers targets for antiobesity drugs, challenges and limitations, failed translation of basic science to clinical practice, methodological and regulatory issues in clinical trials of pharmacotherapy, efficacy and risks of drugs currently approved for obesity, and clinical practice issues when using antiobesity drugs with emphasis on recently approved drugs. Expert opinion: Drugs currently approved for long-term therapy of obesity offer modest benefits for most patients, substantial benefits for some and no benefits for others. Numerous methodological problems including exclusion of the type of patients who are most often seen in clinical practices, inadequate enrollment of men and minorities, exclusion of patients taking antidepressants, high dropout rates, lack of follow-up after treatment discontinuation, and less than ideal imputation methods in data analysis limit the interpretation of clinical trials data and generalizability. Single-drug therapies offer small to moderate weight-loss benefits, but are generally better tolerated. Efficacy is enhanced with combination drug therapies, but so are the hazards. Clinicians should base their decisions on the expected and observed benefit-to-risk balance.Expert Opinion on Pharmacotherapy 02/2014; DOI:10.1517/14656566.2014.890590 · 3.09 Impact Factor