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Arena Pharmaceuticals, Inc. Message Board

  • jeremiahthirtythreeone jeremiahthirtythreeone Jan 23, 2013 1:18 PM Flag

    Belviq lowers glucose by unique mechanism

    This is in response to leviwilliams incorrect statement that Belviq lowers glucose by weight loss making it not unique. I am resposting because my response to his accusations was lost in the YMB format

    Belviq does have a mechanism other than weight loss alone in decreasing glucose:


    5-HT2c receptors (5-HT2c R) have long been implicated in the control of food intake and glucose homeostasis. Evidence comes from both genetic and pharmacological experiments. In fact, new research, within the last 2-3 years has identified 5-HT2c R agonists as potentially useful for type 2 diabetes. This finding was confirmed by utilizing mice that have genetically absent 5-HT2c receptors. These mice develop hyperinsulinemia, type 2 diabetes and obesity as they age.

    Studies utilizing mice without these receptors have changed the view that weight loss alone is sufficient to improve glucose control and insulin sensitivity. A study by Zhou and colleagues [Zhou et al. Serotonin 2C receptor agonists improve type 2 diabetes via melanocortin-4 receptor signaling pathways. Cell Metab 6, 398-405 (2007)] demonstrated that 5- HT2c R agonists had positive effects (improvement of glucose) at doses below those needed to see effects on food intake or body weight, indicating that a weight loss-independent role for 5HT2c R agonist in glucose regulation was operative.

    What this indicates is that glucose control is mediated in the CNS and therefore medications that act on the sites that are responsible for glucose regulation can do so apart from weight loss alone. And this is where lorcaserin has its mode of action – activation of 5-HT2c receptors expressed on proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus. It is here that lorcaserin effects both weight loss and glucose regulation – that is, glucose improvement is not only the result of weight loss but also to lorcaserin’s effect through the POMC neurons as a result of 5-HT2c R agonism.

    This is important with regard to the BLOOM-DM study results. The main endpoint is not weight loss but rather glucose regulation, i.e., hemoglobin A1C levels as the most important indicator of glucose control. It is known that diabetics tend to achieve less weight loss than non-diabetics however this is not as important as the effects of 5-HT2c agonists on glucose homeostasis. Lorcaserin is a selective 5-HT2c R agonist. The studies mentioned above were performed with agonists that were not as selective for the 5-HT2c R as lorcaserin and yet they improved glucose homeostasis without concomitant weight loss. BLOOM-DM had a 0.9% decrease in HgbA1c levels which is very important in reducing the microvascular-related complications that are associated with poorly controlled diabetics. In this trial the percentage of weight loss is not as important as the effect it has on overall glucose regulation. Having said that, they did meet the FDA’s requirement for weight loss – this is truly a unique and extremely promising drug. It attests to the scientific breakthroughs this company is capable of.

    BTW leviwilliams, I do not provide "BS" I provide information from a scientific point of view. If the the interpretations and results don't meet your expectations then do your own research. As far as I can tell you haven't ever provided any useful information so as the saying goes,

    "First get the log out of your own eye and then you will see clearly to take the speck out of your friends eye"


    Sentiment: Strong Buy

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    • Belviq is BELA-UNIQUE

    • great reply,you know your stuff

      Sentiment: Strong Buy

    • bumped

    • GREAT POST!!!

      Sentiment: Strong Buy

      • 1 Reply to trinikajo
      • These 2 Obesity experts disagree with Dr. Dan. They do not believe Lorcaserin lowers a1c independent of weight loss. They say Dr Dan is wrong according to their 2012 Obesity Society Annual meeting presentation in front of their fellow peers.

        Ken Fujioka, MD Director, Nutrition and Metabolic Research, Department of Diabetes and Endocrinology, Scripps Clinic, San Diego, California
        Robert Kushner, MD
        Professor of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois

        Also Belviq's 0.9% reduction in a1c is small relative Qsymia 1.6% reduction in a1c

        The DM-230 study met its primary endpoint of demonstrating glycemic control as measured by a reduction of hemoglobin A1c of 1.6% from 8.8% to 7.2% for subjects treated with Qnexa, as compared to 1.1% from 8.5% to 7.4% in the placebo group (ITT LOCF p=0.0381) at 56 weeks. Subjects in the study were actively managed according to American Diabetes Association (ADA) standards of care with respect to diabetes medications and lifestyle. For subjects treated with placebo, significant increases in the number and doses of concurrent anti-diabetic medications were required to bring about the observed reduction in HbA1c. By contrast, concurrent anti-diabetic medications were actually reduced over the course of the trial in subjects treated with Qnex

    • another great post!!! Bump!!!

      Sentiment: Strong Buy

    • Bump to the top.

      Sentiment: Strong Buy

    • clear_the_mess_away clear_the_mess_away Jan 24, 2013 12:30 AM Flag

      It lowers something? what a funking shocker that is! It sure doesn't lower body mass. non working #$%$...POS is worth a big FAT 0

      Sentiment: Strong Sell

    • Dr Dan,

      The Zhou study you reference bases its conclusions on a few dozen mice and what this study indicates is that glucose control is mediated to some extent through the CNS in mice. Extending the conclusions of this limited study to humans is SPECULATIVE at best. You know this yet your tone is of certainty to an audience of non scientist who don't know how scientific discovery and debate works. This is disingenuous and dishonest.

      The link between 5-ht2c r agonst and decrease in a1c levels has NOT been systematically studied in humans because a highly selective 5-ht2c agonist such as Locaserin hasn't been available to study in humans until now. The health benefits beyond weight control to diabetics is UNKNOWN and completely speculative. There are no completed medical trials, NO FDA approved indications for the use of Lorcaserin in the lowering a1c in diabetics and NO insurance or national health insurance program will pay for such treatment without long term clinical trials and few patients will pay out of pocket for the years of sustained treatment to achieve the theoretical benefits.

      The regulatory, scientific and medical communities come to conclusions about the best treatment options through consensus of many experts weighing the risks and benefits. Experts understand their voice and opinion is but one of many and in the end their opinion may not win out. You should know this yet you present your arguments with an certainty of outcome that suggest to me you are not who you say you are...

      I think you're a BS artist who has a good command of language and is sophisticated enough to couch your arguments in scientific papers and leaps of logic that appeals to peoples desire to find the next big thing, to be apart of maverick movement that nobody else saw coming. And because the topic is obesity and weight, something we can all intimately relate to, we all feel we have a legitimate opinion on the subject. It's personal for many of your followers.

      I just want you to know there are people here who read your posts and see through you. There are people who actually check the source materials you site, recognize the false conclusions you draw, and note how many ARNA longs are overly reliant on your analysis and opinion. However wonderful you may think Lorcaserin may be YOUR opinion means nothing to the CHMP members, your opinion means nothing to the patient faced with the out of pocket expense of Belviq, your opinion means nothing to the insurance or government considering whether to cover Belviq, etc These are the critical opinions an ARNA long should be trying to discern, your opinion ultimately will do nothing for the pps of ARNA.

    • Bump to the top - this is why Belviq will be very successful. Basher, hedgies, shorts, CR's head for the hills. Next year you will all be back in your sewers sucking down the sheet you live in and deserve to live in.....LOL!!!

    • As you stated leviwilliams is full of the BS stuff!

      The following information is from Arena's poster presentation at the 2011 ADA (American Diabetes Association) Scientific Sessions in June 2011:

      Lorcaserin-induced Weight Loss and Glycemic Control in Patients with Type 2 Diabetes Mellitus: Data from the Bloom-DM Study

      In this presentation they show under the heading: Glycemic Control by Study Visit

      There are three graphs. One is a graph of HbA1c by study week that compares placebo to the drug arm. At week 2, the drug group saw a reduction of 0.6% in HbA1c compared to a drop of ~ 0.25%.
      That drop was not weight loss induced at all. Both the placebo and drug groups were taking metformin. Obviously, the drug group was taking Metformin+Lorc.

      The second graph is the reduction of FG (Fasting Plasma Glucose) versus study week comparing placebo to drug arm. At week 2, FG in the drug arm dropped by 23-24%; placebo dropped by 13%.

      The third graph is a measure of HOMA-IR versus study week. At week 2, the drug arm was measured at -0.42 vs. placebo of -0.25.

      At week 12, the drug arm hit a peak reduction in HbA1c of 1.1%. The placebo arm at week 12 reached 0.6% but then went back to 0.5% by week 52. The drug arm went back to 0.9%.

      At week 12, the drug arm hit a peak reduction of FPG of 27-28% and stayed there for the duration of the 52 week study. The placebo hit a peak reduction of FPG of 15% at week 24 but dropped back to 12-13% by week 52.

      At week 12, the drug arm's HOMA-IR dropped to -0.5; the placebo arm went back up to -0.22.
      The drug arm showed HOMA-IR continuing to drop until week 52 to about -0.58; the placebo arm stayed at -0.22.

      I would agree that at about 6-8 weeks the weight loss effect did come into play. The graphs/data clearly show that after only two weeks on Lorcaserin; T2DM patients saw significant drops in the key measures of glycemic control before any significant weight loss had occurred.

      This data supports Dr. Daniel's research that shows that the 5HT2c receptor does play a role in glycemic control independent of weight loss.

      • 1 Reply to jdsstevens55
      • jdsstevens55,

        Ever stop to think lorcaserin just ended some patients craving for sweet foods, dounuts, cakes, cookies, etc???.... you know Occam's Razor? They still consumed the same number of calories in the form of fats and proteins, their a1c went down, but it doesn't resolve the root problem for them. Too many calories in relative to too many calories out. That's the root cause of diabetes, years of over eating. Anything short of bringing down calories in to match calories out at the very least is just addressing the symptoms of diabetes.

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