Enter the Gila
This is where Byetta finally comes in. The peptide found in the Gila monster saliva not only acts at the same receptor as GLP-1, but also lasts longer in circulation, allowing it to be effective throughout much of the day.9,10 The initial promise for Byetta was as a tool to restore some of the insulin-secreting function of the pancreas. However, researchers found that Byetta does much more than that.
When a person is fasting, the body maintains a normal blood sugar level by releasing stored sugar from the liver and creating new sugar from other energy sources.11 Sadly, one of the sources is a conversion of Amino Acids from muscle into sugar. Thus, the liver is churning out new glucose, often at the expense of muscle Amino Acids, during periods when a meal hasn’t been consumed in the last two to four hours. When a meal is consumed, a quick burst of insulin is released, followed by a longer, slower insulin release.12 The purpose of the first insulin spike is to turn off the glucose production/release from the liver. The second, long wave of insulin circulates through the body to help shuttle sugar from the meal into muscle, the liver and other active tissue. GLP-1 plays an important role in promoting the initial burst of insulin as well as the release of insulin in response to eating.13
Using Byetta, diabetics could now replace the deficient GLP-1 with a more potent and longer lasting pharmaceutical substitute. Numerous clinical trials proved Byetta is effective at providing greater sugar control to diabetics. Though this news was well received by clinicians, patients and investors in Amylin Pharmaceuticals, it was the secondary effect of Byetta that caused a major stir among the diabetes community.

The Calorie Connection
As opposed to the other common drugs used in treating this disease, Byetta users were reporting steady, consistent and at times, dramatic weight loss.14 Some users reported losing as much as 60 pounds or more.15 This effect was documented in the clinical trials and investigators provided some insight as to the mechanism for the weight loss.
Byetta, a long-acting GLP-1 analog, restored a normal double-pulse release of insulin to diabetics.16 By shutting down the liver sugar production and release, blood sugars were lower, both after meals and during fasting periods. Also, as the pancreas was sensitive to the sugar in food, insulin was released in a manner that prevented a buildup of sugar in the bloodstream. Additionally, gastric emptying was slower, which means food was held in the stomach longer, before it was dumped into the small intestines where most of nutrient digestion and absorption occurs.17,18 Not only did this prevent overeating by the subjects— in fact, most reported they couldn’t overeat without feeling very distended— but it also allowed sugar from the diet to enter the bloodstream in a more gradual manner. It’s also possible that Byetta somehow affects the satiety center in the brain, cutting off hunger signals more quickly during a meal.19 Between the fullness in the stomach and reduced appetite, Byetta reduces calorie consumption by 20 percent.2
Bodybuilders and dieters have looked to diabetes drugs before for aid in losing fat, including the drugs metformin and acarbose.20 Though there are several studies documenting a fat loss effect from metformin in nondiabetic, obese people, it’s currently not recommended for use as a weight loss aid.21, 22 Acarbose doesn’t appear to offer any significant benefit.23 Also, the late Dan Duchaine introduced 4-hydroxyisoleucine to the bodybuilding community, an amino acid that also has incretin-like effects.24

Advantages & Disadvantages
It’s likely that Byetta is already being used by some bodybuilders, as 8.7 percent of the adult U.S. population has diabetes.25 Further, there are several aspects about Byetta that make it particularly attractive to bodybuilders. First, unlike metformin, Byetta doesn’t carry the risk of lactic acidosis (a buildup of lactic acid in the blood, which is often fatal) and has a much lower risk of hypoglycemia (low blood sugar). It’s also much safer than using insulin, which is used as part of the anabolic cocktail by certain athletes and bodybuilders.26,27
Insulin carries the serious risk of hypoglycemic shock and an overdose of the drug can be fatal. Insulin has been used for the purposes of murder and suicide. Mild-to-moderate nausea is very common with Byetta, but it’s short-lived and goes away as the subject becomes used to the drug.28 Byetta is designed to be injected into diabetics twice a day, but once a day may suffice for someone with normal sugar control. It’s injected under the skin (subcutaneously) using a very short, fine needle, up to an hour before a meal. The drug can be injected into the skin of the arm, thigh or abdomen.29 This is much more comfortable than the longer, larger needles used for anabolic steroids. It’s not listed as a banned substance, thus it poses no problem with drug testing.
As Byetta matches insulin response with eating, the shuttling of nutrients into the muscle should be enhanced; also, insulin levels would fall as soon as food is digested, preventing an overly long signal to store fat.30 As the liver no longer inappropriately produces sugar, muscle amino acid stores would be protected. The sense of satiety and fullness would allow an athlete to maintain a strict diet, reducing the desire to overeat or binge.2
It should be noted that there are some potential drawbacks to the use of Byetta or related drugs in bodybuilders and athletes. As was noted in the published clinical trials, Byetta delays gastric emptying. In addition to making it difficult to eat a large meal, this effect would delay the absorption of any oral drugs or supplements. Also, because of a slower release, oral drugs will also have a lower peak or maximal blood concentration.17
Secondly, GLP-1, the hormone Byetta mimics, reduces energy expenditure, meaning fewer calories are burned during the day.31 Thus, for athletes who are seeking to build mass or put on weight, Byetta may sabotage that effort by reducing feeding; for those looking to get lean, the reduction in thermogenesis may interfere with efforts to lose fat weight. Clearly, time and experience will answer the many questions facing the use of Byetta in weight/fat loss attempts.