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12.01.2011

Lose twelve kilograms with a combination of pramlintide and metreleptin: human study

There may just be a medicine that works against obesity. Researchers at Amylin Pharmaceuticals have done trials with a combination of methionylleptine [Metreleptin] and an adjusted version of the hormone amilyn. Overweight people can lose a maximum of half a kilogram a week with a combination of these two substances.

When the pancreas emits insulin, the beta cells also synthesise the hormone amilyn. Amilyn makes the stomach digest food more slowly, and sends the brain a signal of satiety. A perfect slimming aid, thought some clever pharmacologists – so they set up Amylin Pharmaceuticals. The company launched a version of amilyn that differs from the hormone made in the body by a couple of amino acids, and as a result breaks down less fast. The analogue is called pramlintide, but the bottle containing the substance is labelled Symlin.

Symlin works, according to trials done by Amilyn Pharmaceuticals. [J Clin Endocrinol Metab. 2007 Aug; 92(8): 2977-83.] [Diabetes Technol Ther. 2002; 4(1): 51-61.] Injections of this hormone increase the effectiveness of a weight loss diet, although the results are not earth shattering.

A problem that many overweight people encounter is that their feeling of hunger increases the longer they are on a diet. This is because over-fed fat cells synthesise the appetite suppressing hormone leptin. The disappearance of the leptin seems to be what hampers the dieters most.

Although trials with leptin done at the end of the nineties did not provide convincing results, the researchers decided to give the stuff another try. They combined the synthetic leptin analogue metreleptin with pramlintide.

The researchers got 177 overweight, but not obese, subjects to first go on a diet of 40 percent fewer calories than they burned for 4 weeks. The researchers combined this with 2 injections of 180 and then 360 micrograms pramlintide per day.

Then the real trial started, which went on for 20 weeks. The researchers advised the test subjects to follow a diet containing 20 percent fewer calories than they burned daily, and divided the subjects into three groups. One group was given two injections a day containing 5 mg metreleptin, another group was given two daily injections of 360 micrograms pramlintide, and yet another group was given both treatments.

The worst side effect was the irritation where the subjects were injected. The figure below shows the results for the combination group. The metreleptin injections probably irritate more than the pramlintide injections.

Another side effect was nausea, but this was temporary.

The researchers write that their treatment is promising. "The results of this study provide an initial clinical proof-of-concept for an integrated neurohormonal approach to obesity pharmacotherapy and warrant further development of pramlintide/metreleptin as a weight-loss regimen."

Source:
Obesity (Silver Spring). 2009 Sep;17(9):1736-43.