Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Experimental drug achieves unprecedented weight loss

11.04.2011
An investigational combination of drugs already approved to treat obesity, migraine and epilepsy produced up to a 10 percent weight loss in obese individuals participating in a one-year clinical trial, according to researchers at Duke University Medical Center.

Appearing online in The Lancet today, the study found that treatment with the controlled-release combination therapy consisting of phentermine and topiramate also achieved significant reductions in blood pressure and hemoglobin A1C.

Study participants also experienced improvements in cholesterol, triglycerides and inflammatory markers, including C-reactive protein, when taking either of two doses of the combination when compared to placebo.

"Patients receiving this combination experienced 8.6 percent greater weight loss, on average, compared to those patients receiving placebo," says Kishore M. Gadde, M.D., director of Duke's obesity clinical trials program. "This kind of weight loss, coupled with significant reductions in cardiometabolic risk factors represents a potentially important advancement in the management of obesity."

Currently, orlistat is the only drug available for the long-term treatment of obesity. It is marketed in prescription strength as Xenical, and available over the counter as Alli. Meta-analysis studies have shown that treatment with orlistat, at maximum strength, can lead to approximately seven-pound greater weight loss compared to treatment with placebo after one year. "The combination drug achieves about 19 pounds of weight loss relative to placebo at one year," Gadde says.

The 56-week, phase 3 study was conducted in 93 U.S. centers with 2487 patients who had a BMI of 27-45kg/m2, and two or more co-morbidities such as diabetes or heart disease. Patients were randomly assigned to receive either a placebo or one of two low-dose drug combinations. The study tested phentermine, a short-term obesity treatment available since 1959, and topiramate, marketed under the trade name Topamax, in doses up to 400mg to treat epilepsy and prevent migraines. Patients in the study also received diet and exercise advice.

The study was funded by Vivus, which is seeking FDA approval to market the combination therapy under the trade name Qnexa. In October 2010, the FDA ruled that the New Drug Application could not be approved in its current form, and asked the company for more safety data.

In March, the FDA issued a warning regarding the use of topiramate during pregnancy stating that pregnant women who take the drug are at considerably increased risk of having babies born with cleft lip and/or cleft palate. Topiramate has also been associated with memory problems and mood changes, including depression and anxiety.

Gadde says 34 women became pregnant while in Qnexa clinical trials, and "no birth defects were reported for the babies born." Even so, Gadde says pregnant women would not be candidates for use of this drug because "there is no reason for women to use weight loss drugs while they are pregnant or trying to become pregnant."

The study used once-daily oral doses of the combined drugs. Phentermine 7.5mg plus topiramate CR 46mg achieved 7.8 percent weight loss (p

The greatest improvement in cardiovascular disease and diabetes were seen in high risk patients among the groups given placebo, phentermine 7.5mg plus topiramate 40mg, or phentermine 15mg plus topiramate 92mg respectively:

Systolic blood pressure: -4.9mmHg, -6.9mmHg, -9.1mmHg
Diastolic blood pressure: -3.9mmHg, -5.2mmHg, -5.8mmHg
Total cholesterol: -4.9%, -5.7%, -7.8%
LDL: -3.6%, 0.7%, -4.3%
HDL: 2.8%, 9.5%, 10.7%
Triglycerides: -8.8%, -24.1%, -25.6%
Hemoglobin A1C in diabetics: -0.1%, -0.4%, -0.4%
Fasting insulin in pre-diabetics: 6.0pmol/L, -29.2pmol/L, -31.9pmol/LM
The most common adverse events in the groups given placebo, phentermine 7.5mg plus topiramate 40mg, or phentermine 15mg plus topiramate 92mg, respectively were:
Dry mouth (2%, 13% and 21%)
parethesia (numbness or tingling), (2%, 14%, 21%)
constipation (6%, 15%, 17%)
insomnia (5%, 6%, 10%)
dizziness (3%, 7%, 10%
dysgeusia (distorted sense of taste) (1%, 7%, 10%)
Depression-related events were found in 4 percent assigned to placebo, 4 percent assigned to phentermine 7.5mg plus topiramate 46mg and 7 percent to phentermine 15mg plus topiramate 92mg. Anxiety-related events were reported in 3 percent, 5 percent and 8 percent respectively.

"Although the overall incidence of these events was relatively small," Gadde says, "clearly there is a dose-related increase in risk."

The drug combination works in two ways, he says. Phentermine increases the release of norepinephrine, a brain chemical that may influence hunger and satiety. Topiramate has numerous mechanisms of action including effects on sodium channels, glutamate and GABA transmission, and carbonic anhydrase inhibition, although the mechanism responsible for weight loss is not clearly known.

"We believe it mainly works by reducing hunger and increasing satiety, but may have an independent effect on glucose control," Gadde says. "More patients on placebo developed diabetes during one year than patients who were on the combination drug. More patients on the combination drug were also able to go off their diabetes and blood pressure medicines."

Gadde believes more treatments are needed for obesity as rates increase. "Two thirds of Americans are overweight or obese. For obese patients who have failed to achieve meaningful weight loss with diet and exercise, we have just one treatment before jumping to bariatric surgery. We need more treatment options."

Dr. Gadde has received funding from Vivus for conduct of research studies. He was a paid consultant to Vivus until 2008.

Debbe Geiger | EurekAlert!
Further information:
http://www.duke.edu

More articles from Studies and Analyses:

nachricht Multi-year study finds 'hotspots' of ammonia over world's major agricultural areas
17.03.2017 | University of Maryland

nachricht Diabetes Drug May Improve Bone Fat-induced Defects of Fracture Healing
17.03.2017 | Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Argon is not the 'dope' for metallic hydrogen

24.03.2017 | Materials Sciences

Astronomers find unexpected, dust-obscured star formation in distant galaxy

24.03.2017 | Physics and Astronomy

Gravitational wave kicks monster black hole out of galactic core

24.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>