Qnexa. The next obesity cure?
The FDA just approved Qnexa for the treatment of obesity and obesity related comorbid conditions such as diabetes, cancer and heart disease. Qenexa is the combination of two well-known drugs, phentermine and topiramate. Phentermine is a central norepinephrine releasing drug that has previously (1959) been approved for short-term treatment of obesity. Topiramate is marketed for treatment of migraines and epilepsy. The combination of the drugs is thought to act in an additive or synergistic manner upon the neural and peripheral pathways that control hunger, satiety and energy homeostasis.
The aim of the Conquer Trial was to examine the effect of low dose, controlled – release, phentermine plus topiramate on weight loss and associated comorbid conditions in overweight and obese adults. The study included individuals with a BMI of 27-45kg/m2 that had two or more of the following: diabetes, hypertension, high triglycerides and a waist girth of ≥102 cm for a man and ≥ 88 cm for a woman. 2487 individuals were randomly assigned to receive placebo (P), 7.5mg phentermine + 46 mg topiramate (LPT) or 15 mg phentermine + 92 mg topiramate (HPT) for 56 weeks to assess weight loss as the primary outcome. The benchmark goal of the therapy was a10% reduction in body weight. At the onset of the study, all study patients were given a lifestyle modification manual and encouraged to implement lifestyle changes and reduce caloric intake by 500 calories/day.
Although it has been demonstrated that lifestyle modification programs are effective in reducing weight and improving the comorbidities associated with increased weight. These interventions require trained personnel and frequent office visits. One of the goals of the Conquer Trial is to produce a treatment that can be administered by family doctors without the need for counseling or frequent office visits.
After 56 weeks, change in body weight was -1.4 kg for the placebo group, -8.1 kg for LPT and -10.2 kgs for HPT. Twenty-one percent of P, 62% of LPT, and 15% HPT group achieved a 5% weight loss. Using the 10% weight loss threshold, 7% of P, 37% of LPT and 48% HPT reached the 10% threshold.
According to the authors, these results indicate that phentermine + topiramate with an office-based intervention may be a valuable treatment for obesity that can be safely administered in the family practice setting. I am confused. How can they say that? After 56 weeks, over half of the volunteers did not achieve the 10% weight loss goal. The greatest weight loss was 26.84 lbs, achieved by the high dose group. Furthermore, all participants in the study were instructed to make a 500 calories deficit per day in their food intake. Usually a 500 calorie deficit per day yields a pound/week weight loss. If executed, that is over 50 pounds lost from decreasing caloric intake during 56-week study period. Although study patients were assessed at week 2,4 and every 4 weeks thereafter, it was unclear if calories consumed were discussed.
When did obesity become a disease? Is it when health care and pharmaceutical industries decided they could profit from it? I do believe that being overweight or obese is a complex combination of factors. The fix is not as simple as more exercise or eating less unless humans are laboratory animals, completely controlled. However, human behavior encompasses intellectual, social, emotional, self esteem, and environmental factors. Becoming overweight is an insidious progression of events that show up as excess pounds and poor health. The fix of the problem needs to be unique to each individual. It must address the interaction of their psychological health with the environment they live in. A pill and a few minutes with the family doctor will hardly scratch the surface.
Obesity is classified as monogenic, syndromic or polygenic. Monogenic causes are those that occur from a single gene defect and are present within the first year of life. There are 6 mongenic forms of obesity: leptin deficiency (LEP), leptin receptor gene mutation (LEPR), pro-opiomelanocortin gene mutation (POMC), melanocortin 4 receptor gene mutation (MC4R), Pro-hormone convertase-1 mutation (PC1), and single-minded, drosophilia, homolog of, 1 gene (S1M1) mutation and neurotrophic tyrosine kinase receptor type 2 gene (NTRK2) mutation.
Syndromic obesity occurs in the context of a distinct set of clinical phenomena. There are about 25 such syndromic types of obesity that are identified and they are associated with the clinical pathologies such as mental retardation, dysmorphic features or organ specific developmental abnormalities.
Polygenic obesity is the where multiple common, interacting alleles contribute to the development of obesity. In humans, 61 common gene variants at 58 loci are associated with obesity phenotypes. With polygenic obesity, a poor lifestyle can upregulate the expression of obesity or a prudent lifestyle can stave off the expression of the obese phenotype.
About 70% of adult Americans are overweight or obese. The risk of a child becoming obese is 2.5 – 4 times greater if one parent is obese and up to 10 times higher if both parents are obese. The main thing to keep in mind is that genetic predispositions are like seeds. There are seeds for obesity, heart disease, diabetes, mental illness, etc. The way you live has an enormous influence on what genetic predispositions manifest. If you plant your obesity seeds in fertile soil: energy rich, nutrient poor foods, processed foods, minimal consumption of fruits or vegetables combined with low levels of physical activity; your obesity seed will flourish. If you live so that your obesity gene is starved or neglected, it will likely not flourish.
Unfortunately, medicine and pharmaceutical industry do not want you to feel so empowered. The media and advertising encourage individuals to look at health as out of their hands. Because we can’t choose our parents, get in the driver’s seat of your health and starve the unfavorable genetics we have been given.