The great Dr. Schoeller can polish a turd like no other. Dale Schoeller’s claim to fame is his extensive work on one of the best ways to measure total energy expenditure in free-living individuals: doubly-labeled water. In doubly-labeled water, subjects drink stable isotope-labeled water; instead of hydrogen + oxygen = H20, the stable isotope-labeled water is deuterium + oxygen-18 = D218O. Deuterium is excreted just like hydrogen, in water as urine & sweat. Oxygen-18 is excreted just like oxygen, in water and carbon dioxide. So the subjects lose deuterium & oxygen-18 in water at equal rates, but only oxygen-18 in carbon dioxide; so this technique basically measures carbon dioxide production, which is proportional to energy expenditure. Clever. 
Being that Schoeller practically invented the technique, his interpretation of these total energy expenditure data are not flawed, but that’s not where he went astray.
Alterations in energy balance following exenatide administration (Bradley et al., 2012)
In brief, they used indirect calorimetry to assess respiratory gases, doubly-labeled water for total energy expenditure, and DEXA for body composition before and after a 3-month course of exenatide. Curiously, given their extensive assessment of energy balance, they didn’t measure food intake.
Exenatide is a GLP-1 agonist which enhances glucose-stimulated insulin secretion, suppresses glucagon, and slows gastric emptying. It is effective at controlling blood glucose when combined with other anti-diabetic medications.
To start with the ending:
“by deduction the significant weight loss and loss of fat mass was due to decreased energy intake.” This line of prose nearly swept me off my feet, until I remembered that exenatide makes people sick… literally. As such, it’s one of the few anti-diabetic medications that don’t cause weight gain.
That’s not the only anti-pearl, however. The authors’ skill at math is about equal to a fifth-grade level:
Alternatively:
According to my calculations, they correctly calculate the change in body weight. However, 43.4 minus 42.3 is closer to 1.1 than 1.3, and 58.9 minus 56.9 is closer to 2 than 0.8. In other words, their fuzzy math overestimates fat loss and underestimates muscle loss. Tsk tsk. But that’s beside the point, and it doesn’t markedly affect the energy balance differential; it only attempts to shine a better light on exenatide. Being that this study was designed, reviewed, and edited by the makers of exenatide… never mind, I’m not a big conspiracy theorist. just sayin’
The subjects weren’t hypermetabolic sick, which would’ve been accompanied by increased RMR; they were only oh-my-stomach-hurts sick, so the decline in energy expenditure was due to reduced physical activity.
To all the fans of the Laws of Energy Balance (which admittedly is probably only me), this drug works by enhancing insulin. Low carb diets reduce insulin (they also have the opposite effect on energy expenditure). Any guesses as to why energy expenditure declined with exenatide? High insulin levels? Nausea?
With enhanced insulin levels, this drug is expected to preserve fat mass. So their calculations, which estimate the loss of fat to comprise 62% of the weight lost are less likely than mine, which estimate this to be 35%. You be the judge.
In any case, this statement in the discussion is particularly far from prudent:
Even if fuzzy math was correct, which is contradicted by my calculations and the theoretical mechanism of exenatide action, this statement is way off.
To have deduced this drug reduced body weight by reducing food intake is incomplete. That is far from the only viable explanation (eg, calorie-thieving gnomes). It’s not terribly unlikely, however, given that 40% of the subjects experienced nausea; so severe that 18% dropped out of the study… but losing weight because you’re sick further confirms that muscle contributed to the weight lost.
Furthermore, it wouldn’t be unreasonable to deduce this drug burns muscle. By enhancing insulin, it will preserve fat mass at the expense of fat-free mass… but it will allow you to continue a carb-rich Western diet for a little longer before insulin injections are necessary.
What’s next, tapeworms?
Really? They used top-of-the-line techniques to assess almost every other variable of energy balance but completely overlooked one of the biggest contributor: food intake.
The Law of Conservation of Energy has nothing on the Laws of Energy Balance. Nothing! (maniacal laughter)
