Byetta (Exenatide) v. Taubes

Taubes has 10 major conclusions for GCBC, the ones relevant to this post are quoted below:

5. Obesity is a disorder of excess fat accumulation not overeating and not sedentary behavior.

6. Consuming excess calories does not cause us to grow fatter any more than it causes a child to grow taller. Expending more energy than we consume does not lead to long-term weight loss; it leads to hunger.

7. Fattening and obesity are caused by an imbalance – a disequilibrium -- in the hormonal regulation of adipose tissue and fat metabolism: Fat synthesis and storage exceeds the mobilization of fat from the adipose tissue and its subsequent oxidation. We become leaner when the hormonal regulation of the fat tissue reverses this balance.

8. Insulin is the primary regulator of fat storage. When insulin levels are elevated – either chronically or after a meal – we accumulate fat in our fat tissue. When insulin levels fall, we release fat from our fat tissue and use it for fuel.

9. By stimulating insulin secretion, carbohydrates make us fat and ultimately cause obesity. The less carbohydrates we consume, the leaner we will be.

Whether he believes this or not, Taubes is interpreted to be saying that hormonal imbalance in the absence of a caloric imbalance is the cause of obesity, and carbs are singularly responsible for this.  Of course he contradicts this with his final conclusion (10. By driving fat accumulation, carbohydrates also increase hunger and decrease the amount of energy we expend in metabolism and physical activity), wherein he makes the case for carbohydrates causing a positive energy balance, but that's a topic for another time.

Enter a drug for Type 2 Diabetes:  Byetta aka Exenatide.  According to Wikipedia, Exenatide is a 39-amino-acid peptide an insulin secretagogue with glucoregulatory effects.  It is an incretin mimetic acting like glucagon-like petide-1 (GLP-1).   Byetta works for controlling blood glucose (all quotations come from the Wiki link):

Exenatide augments pancreas response[5] (i.e. increases insulin secretion) in response to eating meals; the result is the release of a higher, more appropriate amount of insulin that helps lower the rise in blood sugar from eating. Once blood sugar levels decrease closer to normal values, the pancreas response to produce insulin is reduced; however, other drugs (like injectable insulin) are effective at lowering blood sugar, but can "overshoot" their target and cause blood sugar to become too low, resulting in the dangerous condition of hypoglycemia.

 So does protein ingestion, but the typical LC theory on that is that this is attenuated by glucagon.  However:

Exenatide also suppresses pancreatic release of glucagon in response to eating, which helps stop the liver from overproducing sugar when it is unneeded, which prevents hyperglycemia (high blood sugar levels).

Byetta tends to cause weight loss in all but the lowest quartile (lowest fourth) diabetics in terms of weight.  How?  Well:

Exenatide helps slow down gastric emptying and thus decreases the rate at which meal-derived glucose appears in the bloodstream.

Exenatide has a subtle yet prolonged effect to reduce appetite, promote satiety via hypothalamic receptors (different receptors than for amylin). Most people using Exenatide slowly lose weight, and generally the greatest weight loss is achieved by people who are the most overweight at the beginning of exenatide therapy. Clinical trials have demonstrated that the weight reducing effect continues at the same rate through 2.25 years of continued use. When separated into weight loss quartiles, the highest 25% experience substantial weight loss, and the lowest 25% experience no loss or small weight gain.

So ... increased insulin is associated with weight LOSS in overweight/obese, a "side effect" sustained for over two years of continued use.  Byetta is commonly used before the morning and evening meals.  Weight loss is associated with, tada!, decreased food consumption.

Imagine that.  Take in fewer calories, lose weight.  Do you suppose that we become overweight by eating too much in the first place??