Am J Clin Nutr. A meta-analysis of 14 studies comprising 7, participants that reported the results of dominant genetic models indicated a 0. Borel et al conducted a prospective intervention study in viscerally obese men classified according to their glucose tolerance status. The study was limited due to its retrospective medical record review design and lack of a comparator group. The latest health and science updates, breakthroughs, research, and the best in investigative and informative journalism. On average, participants who took Qsymia lost 8. A total of 9 trials were identified and 6 were included. Mean, Median, and Mode: Measures of Central Tendency: Crash Course Statistics #3
In addition to phentermine, which is approved for the short-term treatment 3 months of obesity, two additional agents are approved for longer term use. Orlistat is a lipoprotein lipase inhibitor available in prescription mg and over-the-counter formulations 60 mg , which works by inhibiting the breakdown and absorption of dietary fat. This results in a toxicity profile consisting of gastrointestinal adverse effects, but relatively few serious side effects.
However, the efficacy of orlistat is modest. A meta-analysis of orlistat trials of at least 12 months in duration showed a mean weight loss of 2. Lorcaserin is a serotonin 2C agonist that was recently approved by the FDA for weight loss at a dose of 10 mg twice daily. In three large, controlled trials lasting 52— weeks, including approximately 8, patients, placebo-subtracted weight loss was 3.
The most common adverse effects of lorcaserin in patients without diabetes included headache, dizziness, fatigue, nausea, dry mouth, and constipation. In diabetic patients, the most common side effects included hypoglycemia, headache, back pain, cough, and fatigue [ 21 ]. In October , the FDA requested additional data from Vivus, its manufacturer, to address these concerns. Phentermine, with a history of use spanning 52 years, is currently the most widely prescribed drug for weight loss in the US with over 6.
Topiramate has a year history of use. The drug combination is formulated to produce peak exposure to phentermine in the morning and peak concentrations of topiramate in the evening [ 22 ]. The scientific rationale for the specific doses included in the combination is not clear, for example, 92 mg topiramate instead of the commercially available mg dosage form of topiramate. The doses of topiramate used for weight loss are somewhat lower than for the other indications of the drug.
For weight loss, the recommended dosing is 3. If the dose is escalated, it should be done by prescribing the When discontinued, the drug should be reduced gradually by taking a dose every other day for at least a week before stopping treatment to prevent the precipitation of seizures [ 25 ]. It has been suggested that topiramate and phentermine may have synergistic effects toward weight loss [ 26 ], although this theory has not been tested in clinical trials.
Topiramate is currently FDA-approved for the treatment of seizure disorders and prophylaxis of migraine headaches [ 23 ]. The mechanism of action that contributes to weight loss is currently unclear. The pharmacology of topiramate is complex. Topiramate has been associated with weight loss in many treatment trials, including epilepsy [ 24 ], migraine headache [ 27 , 28 ], bulimia nervosa [ 29 , 30 ], binge-eating disorder [ 31 , 32 ], antipsychotic-associated weight gain [ 33 , 34 ], and obesity [ 35 ].
A recent meta-analysis [ 35 ] evaluated weight loss associated with topiramate across 10 randomized, controlled trials RCTs in overweight or obese patients, with or without comorbid conditions. Overall, patients lost an average of 5. There were, however, statistically significant reductions in mean BMI, body fat ratio, and abdominal skin-fold measurements. The findings of this study led the authors to conclude that the anorexigenic activity of topiramate may occur through hypothalamic activity.
It has been suggested that topiramate may also lead to weight loss through increased satiety due to decreased gastrointestinal motility, increased taste aversion, increased energy expenditure, and decreased caloric intake [ 22 ]. The propensity of topiramate to contribute to neuropsychiatric and cognitive events at higher dosages has hindered its development as a monotherapy for weight loss [ 37 ].
Phentermine was approved by the FDA in Appetite reduction associated with phentermine is thought to be centrally mediated, including hypothalamic stimulation that results in norepinephrine release [ 23 ]. Phentermine is indicated for short-term use for weight reduction, in combination with a reduced calorie diet and exercise [ 23 ].
The utility of phentermine when used short-term according to its labeling is questionable. Off-label use of phentermine has been examined in clinical trials of longer duration. A meta-analysis [ 20 ] evaluated the results of six placebo-controlled RCTs. The average weight loss in these trials was 3. Phentermine is generally well-tolerated. Common side effects are characteristic of sympathomimetic amines, including dry mouth, headache, insomnia, nervousness, irritability, and constipation.
More serious side effects include palpitations, tachycardia, and hypertension [ 38 ]. Phentermine should be avoided in patients with hyperthyroidism, glaucoma, agitated states, advanced arteriosclerosis, symptomatic cardiovascular disease, moderate-severe hypertension, a history of substance abuse, or those who would have a drug interaction e.
Study name, primary author, year, study sponsor. Study duration, study design, intervention s. The study included a blinded 4-week titration period and subsequent week treatment period. Patients were relatively free of comorbid conditions. Participants were randomized in a 2: Patients were randomized in a 2: Patients continued the product to which they were originally randomized, in conjunction with lifestyle modification.
Percentage rates of participation were as follows: Study completers lost A completer analysis revealed similar results. In three large approximately 8, patients lorcaserin RCTs of 52— weeks duration, weight loss was 3. Other AEs more common with drug: Other dose-related trends dry mouth, constipation, dysgeusia, paresthesia, insomnia, dizziness, anxiety, irritability, disturbance in attention. Additional information on study-specific adverse events may be found in Table 2.
It is thought that the inhibition in carbonic anhydrase that occurs with topiramate contributes to changes in bicarbonate, potassium, and risk of nephrolithiasis. When looking at laboratory results overall, there were no differences between the medication and placebo groups regarding the incidence of serious laboratory-related adverse events or drug discontinuations due to laboratory adverse events [ 22 ]. There were, however, some notable laboratory findings reported in the major trials.
More information on laboratory abnormalities that occurred during clinical trials can be found in Table 2. Mean PHQ-9 scores indicated improvements in depressive symptoms over time in all treatment groups, with no between group differences observed. Data presented in study appendices reflect that there may be a small number of patients whose psychiatric function worsens while on the drug.
Psychiatric and neurocognitive effects have not been specifically and thoroughly assessed in patients with clinical depression or other significant mental health disorders. In all cases, cognitive disturbances resolved after drug discontinuation. In SEQUEL, there was no apparent increase in serious suicidal ideation or suicidal behavior as assessed during the weeks of observation. Depression-related adverse events were comparable between groups.
Anxiety-related adverse events correlated with higher doses. Rates of anxiety were found to be 3. Topiramate is currently marketed in Pregnancy Category D. In some cases, topiramate may be continued during pregnancy when the risk of seizures in a woman with epilepsy or severe migraines outweighs the potential for fetal malformation [ 22 ].
Other sources of data concerning fetal risk with topiramate are being evaluated. To date, it appears that during the first trimester of pregnancy, topiramate has no overall effect on the prevalence of major congenital malformations, but may increase the prevalence of oral clefts by two- to fivefold. Data are currently too limited to conclusively determine the true teratogenic potential of topiramate. Of these, six resulted in abortion three spontaneous, three elective , and nine resulted in healthy live births with no evidence of congenital malformation.
The pregnancy in the drug group was carried to term with no evident teratogenic effects. An additional consideration is that topiramate may interfere with the pharmacokinetics of hormonal contraceptives. The manufacturer states that these changes are unlikely to affect contraceptive effectiveness, although irregular bleeding may occur [ 25 ]. It is recommended by the manufacturer that women of childbearing potential produce a negative pregnancy test at baseline and monthly thereafter during therapy.
This drug will be dispensed only through pharmacies certified by the manufacturer. Among psychiatric side effects, anxiety symptoms seem to be most common. Steffen is the guarantor for this article, and takes responsibility for the integrity of the work as a whole. Kolotkin has received financial compensation for previous consulting work for Vivus and Orexigen. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits the use, distribution, and reproduction in any medium, provided the original author s and source are credited.
Combination Products in Therapy January , 2: Introduction Obesity leads to premature death [ 1 ] and impairs quality of life [2—4]. Topiramate It has been suggested that topiramate and phentermine may have synergistic effects toward weight loss [ 26 ], although this theory has not been tested in clinical trials. These trials provide efficacy and tolerability information regarding the effect of this drug combination on comorbid conditions.
The published trials include: The results of each of these trials will be discussed in detail and a summary of each is presented in Table 1 [ 37 , 39 , 40 ]. Study name, primary author, year, study sponsor Study duration, study design, intervention s Participants: N , characteristics Efficacy: Significant improvements were observed for waist circumference, blood pressure, lipids, glycemia, C-reactive protein, and adiponectin.
Improvement in comorbidities can be reviewed in Table 2 [ 37 , 39 , 40 ]. HbA 1c in type 2 DM subgroup: This includes any medical conditions you may have, your age, starting weight, gender, dietary changes you make and your activity level, among others. Several factors are not things you can control. At the same time, many are factors you can change. It should also be noted that phentermine does not cause weight loss on its own.
If you make no changes at all to your eating and exercise habits, taking this drug will not reduce your body fat. This pill works by reducing your appetite and boosting your energy levels. The goal of taking this pill is to make those other lifestyle habits easier to achieve and establish. Still, as phentermine is associated with a spectrum of side effects and a risk of addiction and withdrawal symptoms, many people choose an alternative to this pill, keeping the prescription as a last resort.
Fortunately, many people can avoid having to take it altogether when they choose the right alternative strategy. It is quite common for dieters to look to Phentramin-d to give them the appetite suppressants and energy boosters they want, without having to fall back on a prescription medication. You can use these HTML tags. Email will not be published required. A sample text widget.