In the JournalsPerspective

Exenatide may increase satiety in adults with Prader-Willi syndrome

A single injection of exenatide 10 mcg helped adults with Prader-Willi syndrome experience improvements in satiety, glucose levels and insulin secretion, researchers reported in a recent study.

Hyperphagia, a classic characteristic of Prader-Willi syndrome, is a major contributor to the obesity often exhibited by patients with the disease. Because exenatide (Byetta, Amylin Pharmaceuticals) has demonstrated positive results for weight loss and satiety in obese patients, researchers in Australia explored the drug’s potential as a treatment for adults with Prader-Willi syndrome.

The researchers randomly assigned eight patients with Prader-Willi syndrome and 11 obese patients without the syndrome to receive a 10-mcg subcutaneous injection of exenatide or normal saline (Pfizer) before consuming a 600-kcal meal. Blood samples were collected before and during the meal and at various points postprandially.

Exenatide increased satiety (P=.03), decreased glucose (P=.004), boosted insulin secretion rates (P=.002), and elevated insulin (P=.004) and C-peptide concentrations (P=.003) in all patients. During the meal, increased ghrelin and peptide YY (total) levels were also noted in patients with Prader-Willi syndrome. After the meal, exenatide eliminated the meal response of peptide YY (total) (P<.0001) and considerably diminished peptide YY (3-36) (P=.002) and glucagon-like peptide 1 (P=.01). The drug had little effect on ghrelin (P=.11).

Nine obese patients experienced adverse effects, including bloating, nausea and vomiting; no events were reported in the patients with Prader-Willi syndrome. However, the researchers said the lack of adverse events in this population may be due to the high threshold for pain and nausea in patients with Prader-Willi syndrome.

Although this study provides data that demonstrate the safety and efficacy of exenatide use in patients with Prader-Willi syndrome, the researchers encouraged confirmation of these results in larger, prospective studies.

Disclosure: The researchers report no relevant financial disclosures.

PERSPECTIVE

Jennifer Miller, MD
Jennifer Miller

Sze et al reported the effects of a single dose of exenatide on appetite and appetite-regulating hormones in adults with Prader-Willi syndrome (PWS), as well as adults with obesity and type 2 diabetes. This article provides interesting pilot data regarding the possibility that GLP-1 agonists may work to decrease appetite in individuals with PWS. The authors report decreases in subjective hunger measurements, as well as in PYY, GLP-1, and insulin levels, with improved insulin secretion after a dose of exanatide in both individuals with PWS and those with obesity. These are stimulating data that GLP-1 agonists may possibly improve satiety in this syndrome, for which there is no treatment for the life-threatening appetite drive at this point.

There are several caveats of this study which must be noted. The first is that appetite was not assessed by measuring actual consumption of food after the dose of medication, but rather by having the participants complete appetite-rating scales. Although appetite scales have been used in the PWS population, it remains to be seen if the answers these patients provide will correlate with actual food consumption or not. Secondly, as the authors note, there is a significant risk of worsening delayed gastric emptying, which is already present in individuals with PWS, with exenatide. The authors make an excellent point of noting that the lack of side effects of exenatide in the PWS population may indicate abnormal appetite regulation, possibly due to abnormal GLP-1 signaling in the brain. Thus, even though the results of this initial study indicate that exenatide improves the sense of satiety, there is no guarantee that it will decrease appetite drive or food consumption in this unique population, which could result in life-threatening complications. Consequently, since it is unclear if exenatide will truly decrease food consumption, there is significantly increased risk for the development of gastric necrosis if the treated individuals consume excess food. Therefore, as the authors note, all trials of this medication will need to be performed in very controlled settings with constant supervision of the individuals.

Overall, this study provides interesting pilot data on the effects of exenatide in adults with PWS, but many questions and concerns about the safety and efficacy of GLP-1 agonists in this syndrome have yet to be answered.

– Jennifer Miller, MD
Assistant Professor
Department of Pediatric Endocrinology
University of Florida

Disclosure: Dr. Miller reports no relevant financial disclosures.

Twitter Follow EndocrineToday.com on Twitter.

A single injection of exenatide 10 mcg helped adults with Prader-Willi syndrome experience improvements in satiety, glucose levels and insulin secretion, researchers reported in a recent study.

Hyperphagia, a classic characteristic of Prader-Willi syndrome, is a major contributor to the obesity often exhibited by patients with the disease. Because exenatide (Byetta, Amylin Pharmaceuticals) has demonstrated positive results for weight loss and satiety in obese patients, researchers in Australia explored the drug’s potential as a treatment for adults with Prader-Willi syndrome.

The researchers randomly assigned eight patients with Prader-Willi syndrome and 11 obese patients without the syndrome to receive a 10-mcg subcutaneous injection of exenatide or normal saline (Pfizer) before consuming a 600-kcal meal. Blood samples were collected before and during the meal and at various points postprandially.

Exenatide increased satiety (P=.03), decreased glucose (P=.004), boosted insulin secretion rates (P=.002), and elevated insulin (P=.004) and C-peptide concentrations (P=.003) in all patients. During the meal, increased ghrelin and peptide YY (total) levels were also noted in patients with Prader-Willi syndrome. After the meal, exenatide eliminated the meal response of peptide YY (total) (P<.0001) and considerably diminished peptide YY (3-36) (P=.002) and glucagon-like peptide 1 (P=.01). The drug had little effect on ghrelin (P=.11).

Nine obese patients experienced adverse effects, including bloating, nausea and vomiting; no events were reported in the patients with Prader-Willi syndrome. However, the researchers said the lack of adverse events in this population may be due to the high threshold for pain and nausea in patients with Prader-Willi syndrome.

Although this study provides data that demonstrate the safety and efficacy of exenatide use in patients with Prader-Willi syndrome, the researchers encouraged confirmation of these results in larger, prospective studies.

Disclosure: The researchers report no relevant financial disclosures.

PERSPECTIVE

Jennifer Miller, MD
Jennifer Miller

Sze et al reported the effects of a single dose of exenatide on appetite and appetite-regulating hormones in adults with Prader-Willi syndrome (PWS), as well as adults with obesity and type 2 diabetes. This article provides interesting pilot data regarding the possibility that GLP-1 agonists may work to decrease appetite in individuals with PWS. The authors report decreases in subjective hunger measurements, as well as in PYY, GLP-1, and insulin levels, with improved insulin secretion after a dose of exanatide in both individuals with PWS and those with obesity. These are stimulating data that GLP-1 agonists may possibly improve satiety in this syndrome, for which there is no treatment for the life-threatening appetite drive at this point.

There are several caveats of this study which must be noted. The first is that appetite was not assessed by measuring actual consumption of food after the dose of medication, but rather by having the participants complete appetite-rating scales. Although appetite scales have been used in the PWS population, it remains to be seen if the answers these patients provide will correlate with actual food consumption or not. Secondly, as the authors note, there is a significant risk of worsening delayed gastric emptying, which is already present in individuals with PWS, with exenatide. The authors make an excellent point of noting that the lack of side effects of exenatide in the PWS population may indicate abnormal appetite regulation, possibly due to abnormal GLP-1 signaling in the brain. Thus, even though the results of this initial study indicate that exenatide improves the sense of satiety, there is no guarantee that it will decrease appetite drive or food consumption in this unique population, which could result in life-threatening complications. Consequently, since it is unclear if exenatide will truly decrease food consumption, there is significantly increased risk for the development of gastric necrosis if the treated individuals consume excess food. Therefore, as the authors note, all trials of this medication will need to be performed in very controlled settings with constant supervision of the individuals.

Overall, this study provides interesting pilot data on the effects of exenatide in adults with PWS, but many questions and concerns about the safety and efficacy of GLP-1 agonists in this syndrome have yet to be answered.

– Jennifer Miller, MD
Assistant Professor
Department of Pediatric Endocrinology
University of Florida

Disclosure: Dr. Miller reports no relevant financial disclosures.

Twitter Follow EndocrineToday.com on Twitter.