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Volume 3, Issue 1 MERIDIA SURVEY RESULTS
In February 1998, Meridia (sibutramine hydrochloride monohydrate) was approved in the United States for treatment of obesity. In clinical trials, 85 percent of subjects lost 5 percent of initial body weight, and 57 percent lost 10 percent. Fifteen percent of subjects did not lose any weight or gained weight taking this medication. (see table below) Meridia is available in 5, 10 and 15 mg capsules. The minimum effective dose is 10 mg. Physicians may increase the dose to 15 mg in patients who do not respond to 10 mg, provided there are no adverse side effects. Meridia is indicated for weight loss in patients with a body mass index (BMI) of 30 or more, 27 or more if comorbidities exist, like type-2 diabetes, high blood pressure, high cholesterol, or a family history of these conditions. For an in-depth monograph on Meridia see the December 1997 edition of Obesity-news, and this month's Obesity-news for a review of existing studies on sibutramine. The purpose of the Obesity-news survey was to get feedback on the efficacy of Meridia from patients in a non-clinical trial setting. This evaluation includes a comparison of efficacy in patients who have taken other medications versus those who have not. The Obesity-news Meridia survey, which went on-line in September 1998, gathered the following information:
The final surveys were accepted on December 30, 1998. Of the 470 responses 51 were e-mail comments leaving 419 surveys. The minimum information required to be included in this evaluation were age, sex, Meridia dose, length of treatment, and the number of pounds lost or gained. All surveys not meeting this minimum requirement were eliminated from the results. Several patients filled out more than one survey. In the case of duplication, the most recent survey was used and the earlier response discarded; 339 surveys met the minimum criteria. Limitations of this survey. This survey is not a scientific study. Respondents were allowed to answer anonymously, and the accuracy of the information provided cannot be verified. Although these statistics are not verifiable, they are similar to results reported to Obesity-news by health care providers. These survey results are not reported in percentage of body weight lost, and Obesity-news did not solicit a starting weight from respondents. Unlike a clinical trial which reports statistics on patients taking medication for a predetermined period of time, respondents to the Obesity-news Meridia survey were in all stages of weight loss, and patients took medications for varying lengths of time. Reporting weight loss in percentage of total body weight is meaningless when comparing patients who took medication for 4 weeks with patients took it for up to 40 weeks, and varying lengths in between.
The table at left profiles respondents by age and sex. Of the 339 participants, 219 (65%) had used another obesity medication prior to Meridia for 1 to 156 weeks. Almost a third (31%) of respondents failed to lose any weight at all (69), or gained weight (35). Out of the 69 who lost no weight, 25 had only taken Meridia for a week and a total of 34 for less than a month. But other subjects, who did lose weight, failed to achieve a significant weight loss even after lengthy treatment. There are several explanations for the variance between results in this survey versus reports from controlled studies, including advice and follow-up on diet and exercise regimens, and support. In addition, some sibutramine trials had a drop out rate of close to 50 percent. In many cases the reason for withdrawal was not known, although 15 percent were attributable to lack of efficacy. Finally, it is unlikely that former users of other obesity medications were used in trials, or in the numbers seen in this survey. Published sibutramine studies did not report previous obesity medication use, so it is an unknown factor.
Patient response to Meridia varied widely in this survey. Respondents lost as much as 85 pounds and gained as much as 25 pounds. There was a linear progression in the number of pounds lost per week according to the amount of weight lost in total. Respondents who lost more than 30 pounds on Meridia lost an average of 2.9 pounds per week. Those who lost 20-29 pounds 2.2 pounds per week, 10-19 pounds 1.4 pounds per week, 5-9 pounds 1.2 pounds per week, and 1-4 pounds .48 pounds per week. Some patients lost as much as 5 or 6 pounds per week, but responders who took Meridia for more than 20 weeks averaged a 1 - 2 pound weight loss per week, even in the highest weight loss category. Overall, survey respondents did not lose weight successfully taking Meridia. Of the 248 participants who took Meridia for more than four weeks, 134 lost 1 pound or more per week. 99 were clear non-responders. A few gained weight, but most lost no weight or just a few pounds; 15 were marginal responders. The overall failure rate was 45 percent in patients who took Meridia for more than four weeks. Prior obesity medication use and Meridia efficacy.
The biggest challenge in evaluating the statistics in this survey was to determine what effect, if any, prior medication use had on the efficacy of Meridia. Because almost two-thirds of respondents took other obesity medications prior to Meridia, a difference in efficacy was not apparent at first glance. We took two approaches in determining the effect of prior medication use on Meridia efficacy. First we looked at a "snapshot" of respondents who took Meridia for four weeks, and second we compared efficacy by prior obesity medication use. "Snapshot" of respondents at 4 weeks of treatment.Clinical trials on Meridia indicate that responders lose 1.8 kg (4 pounds) or 1 percent or more of initial body weight within the first 4 weeks of treatment. Because a clear definition of success at four weeks exists, we looked at the 47 survey respondents who took Meridia for that period of time. Of the 26 who lost 4 pounds or more, 50 percent (13) had taken other medications. Of the 21 respondents who did not lose 4 pounds or more, 80 percent (17) had taken other obesity medications. While the 30 point spread between responders and non-responders was marked, the group was fairly small, and represented only a handful of patients. Further confounding these statistics, was the success experienced by some patients who formerly took other obesity medications. Of the nine patients who lost more than 15 pounds in four weeks, three were former phen/fen patients, and one took an unspecified obesity medication. The duration of phen/fen use was between 15 and 36 weeks, and weight loss between 30 and 65 pounds.
Comparison by prior obesity medication use.In order to evaluate a larger group of patients, we looked at efficacy by prior obesity medication use in the 248 respondents who took Meridia for more than 4 weeks. Since almost all survey participants had taken Meridia for less than 26 weeks, they should not have reached maximal weight loss. We therefore set the dividing line between responders and non-responders at a weight loss of 1 pound per week. Of the 248, 82 had no history of obesity medication use, and 166 used a variety of medications, including phen/fen, phentermine, fenfluramine (Pondimin), dexfenfluramine (Redux), phendimetrazine, and mazindol. This is where we found the "smoking gun". Of the 82 who took Meridia for more than four weeks but had not used other medications, 68 (83%) of respondents lost a pound per week or more. The 17 percent non-response rate closely parallels that seen in clinical studies. But patients who formerly took other medications did very poorly. Only 66 lost 1 pound or more per week, a failure rate of 60 percent. Why did former obesity medication users do so poorly on Meridia?Both phentermine and fenfluramine are releasers and reuptake inhibitors, phentermine acting on dopamine and norepinephrine and fenfluramine on serotonin. Meridia, as a reuptake inhibitor only, is not as potent as phen/fen was, and clinical studies show much more modest weight loss with Meridia than with phen/fen (5-10 percent versus 15.9 percent). Tolerance could play a factor as well. Some respondents took phen/fen and other medications for up to three years. 
Sibutramine is a chemical that affects the reuptake of norepinephrine and serotonin (SNRI), and has almost no effect on dopamine. Because Meridia is a single capsule, physicians are unable to titrate dose in the same manner they could with phen/fen. The dose of Meridia can be increased or decreased within a small range, but if patients experience nervousness or sleepiness, raising the dose will mostly likely increase the side effect, and lowering the dose may reduce efficacy considerably. With phentermine and fenfluramine, physicians could raise or lower the dosage of either medication to optimize effectiveness, and minimize side effects. This is not possible with Meridia, and Knoll's warning against using Meridia in conjunction other CNS stimulants or depressants, makes it less likely that this medication could be properly adjusted for patients who feel nervous or sleepy. Patient expectations.Patient expectations also played a part in the response. Former phen/fen and Redux patients were disappointed with the much more modest anorectic effect of Meridia. Even patients who lost a significant amount of weight using Meridia were dissatisfied with the results and with the side effects as compared to other medications. A male patient who lost 20 pounds in 12 weeks and a female patient who lost 15 pounds in 12 weeks each said they stopped taking Meridia because it didn't work. The female patient, although she lost 15 pounds while taking Meridia, also said that it increased her appetite. Other patient comments included, "I never felt that Merida helped stop the constant thought of food go away like phen/fen". "When [Meridia] "expires" around twelve hours later I feel ravenous . . . so I must eat something before I go to bed." Many found that Meridia increased their appetites and caused bloating. One patient, who had never taken Redux or phen/fen, put it quite succinctly, "In researching Meridia on the internet, I have come across more negative comments than positive. It seems that the people who are pleased with Meridia's performance are those who have never taken meds before, and those that are displeased have had previous experience with Redux and/or phen/fen . . . . [S]o it may be possible that those of us who never experienced those meds just don't know what we missed, hence, our satisfaction with Meridia." Meridia and other CNS medications.
Some of the patients who took other medications with Meridia did well, and some did not. One of the two patients who took Meridia with phentermine lost 15 pounds in 4 weeks, but the other lost no weight in 16 weeks. The same pattern occurred in the 7 people who took antidepressants. Both patients taking Prozac experienced clinically significant weight loss, the patients on Zoloft were a mixed bag, and the Trazodone patient, who had taken Meridia for a week, was off to a good start with a 3 pound weight loss. The patient taking two doses of Meridia per day was a marginal responder, losing 15 pounds in 20 weeks. But there were too few patients in the sample to draw any conclusions. Most physicians heeded the warning, and would not prescribe Meridia with other CNS stimulants or depressants. This caused a problem for some patients with depression problems. One respondent, who had already stopped taking Meridia, complained "Meridia caused depression. I would like to take [it] with Zoloft, but am told this is not possible." Others stopped taking Meridia because they were depressed and missed their antidepressants, which had been discontinued upon starting Meridia. Meridia as an antidepressant.However, some participants found Meridia to be an effective antidepressant that also caused clinically significant weight loss. One of the most successful Meridia patients in this survey found that the medication made a significant improvement with her life-long depression problems. "I find Meridia to have an effect on my mood. I have been suffering with depression for 30+ years and have taken every antidepressant available without good results, including Zoloft and Prozac. This is the first time I have been free of depression, without side effects in my adult history. I am also having the benefit of weight loss." Another respondent commented, "I have been treated for depression in the past but actually have found that Redux and Meridia keep me even keeled with little sign of depression." Side effects.
Minor side effects were common with Meridia. The most commonly reported side effect was dry mouth (90 patients) and sleepiness (34). But these side effects did not stop patients from continuing to take the medication. There were few serious side effects, but some, including hypertension, heart arrhythmias, rapid heart rate, serotonin syndrome and embolism (blood clot) resulted in cessation of therapy. Hypertension. Five patients who stopped taking Meridia reported rising blood pressure, but one patient commented that the weight loss actually caused her blood pressure to fall. Some patients who had hypertension also reported headaches and nausea. Several reported headaches without a rise in blood pressure. In most of these cases the headaches abated with time. Heart arrhythmias. Three patients reported irregular heart beat. One commented, "After taking [Meridia] for 4 weeks I had severe heart palpitations. Enough to scare me into the ER." Another respondent reported atrial fibrillatioin. A third complained of "a very rapid irregular heartbeat" after 2½ months on Meridia. This patient was also rushed to a hospital emergency room. Rapid heart rate. Two patients reported rapid heart rate. One patient who took Meridia for 12 weeks experienced rapid heart beat while exercising. She commented, "One day after walking my five miles . . . my heart started racing, then it felt like it stopped for a second, and then I started losing consciousness. [After that] I was taken off the drug." Another patient experienced a significant increase in heart rate >140, akathesia (restlessness), significant agitation, and had to be evaluated in the emergency department of local hospital. She was taken off Meridia. Rare side effects.Individual patients reported the following adverse reactions after taking Meridia:
Reasons for discontinuing Meridia.124 respondents (37%) had stopped taking Meridia by the time they took the Obesity-news survey, the primary reason being lack of efficacy (74%).
This is not surprising, considering the failure rate in patients who had taken other obesity medications prior to Meridia. Of the 124 who discontinued medication, 102 (82%) had used other obesity medications. Outside of efficacy, the most often cited reasons for stopping Meridia were cost (40%) and side effects (23%), but very few patients said these factors were their only reason for stopping Meridia. Almost all respondents who said cost was a consideration, and 17 of the 29 who cited side effects, also said Meridia didn't work. Serious side effects were rare among survey respondents, and very few patients were directed by their physicians to discontinue therapy (see section on side effects, above). There was no one question on this survey which provoked more emotion than the cost of Meridia. In addition to the 49 patients who cited cost as a factor for discontinuing Meridia, another 15 who were still taking the medication thought it was too expensive. Five patients said that cost was their only reason for discontinuing Meridia, and of those 5 respondents 4 of them were doing quite well losing weight.
A patient who lost 25 pounds in 8 weeks said, "I would like to continue taking Merida, but when my prescription runs out, I will have to stop because of the cost. I find that Merida is working quite well for me, but I cannot spend over $100 a month for medication." Another respondent, who was still taking Meridia, said "The cost of Meridia is excessive in my opinion, and is not covered by insurance. I'm not sure that the drug caused the weight loss as much as the cost made me determined that I had to have some result." Only two patients said they thought Meridia was well worth the cost, and one non-responder said she would pay any amount of money if she could only find an effective obesity medication. Insurance reimbursement and other factors.Although a great number of patients were dissatisfied with the price of Meridia, at a retail price of $3-$4 per capsule, it is not more expensive than many other newly patented medications, including Viagra (at $10 per pill). But unlike Viagra, the cost of Meridia is generally not covered by insurance policies. Out of the 339 patients answering this survey, only one patient, who was taking the medication for diabetes control, mentioned insurance coverage for Meridia or for the doctor bills. The only other respondent who received Meridia at no cost was part of a clinical trial. Patients who had taken phen/fen at half the cost were the most upset at having to pay for Meridia, and this is understandable since it was not effective for most of them. Socioeconomic status also may play a role in how likely a patient is to feel depressed or angry at the cost of Meridia. Obesity-news did not collect demographic information in this survey, but many patients who were upset with the cost of Meridia also mentioned being on a fixed income, or said Meridia was not affordable to them. Health care practitioners were very disappointed with the results of Meridia. In addition to the comments below, Obesity-news has spoken with physicians privately and at the American Society of Bariatric Physicians meeting last December. One physician had better success prescribing a low dose of phentermine with Meridia, and another prescribed doses above 15 mg. But most practitioners I spoke with had little success with Meridia. And many were reluctant to prescribe it to their patients, knowing that the majority of them would be unsuccessful, and then come for their return visit angry over the cost of the medication. The comments below were e-mailed to Obesity-news by health care practitioners who were aware of the Obesity-news survey. "I've had around 10 patients on Meridia so far come back for their one month visit and the results have been disappointing. Only 1 had a greater than 4 pound weight loss (another had 3.5) and most have said that they feel hungry all the time, some [were even hungrier while taking] Meridia . . . . I had great hopes for Meridia, but frankly I have had much better results with phentermine alone." "We have seen little results with Meridia. I also see more side effects, like blood pressure increases and sleepless/restless nights, I have had a couple of people complain of decreased libido, and men have complained of being unable to keep an erection . . . . Many patients have gained weight . . ." "We [have] had over 50 patients start Meridia and all of them have discontinued [therapy] because it did not work and was too expensive to increase the dosage to an amount that would have been therapeutic." "From a patient who lost 37 pounds in 24 weeks, "I have been told by my doctor that I am one of the few patients [in his practice] that Meridia has worked as well on so far." The only positive experience I've heard came from a nurse practitioner this week. She said, "I have had an interesting experience as a prescriber of Meridia. It had been out about 9 months before Knoll started advertising it to the public. Before the advertising started, I had basically nobody with good weight loss success . . . . After the advertising, I have had quite a few people do very well on it. Granted the sample size is somewhat larger now, but it is interesting nonetheless. The power of positive thinking . . . . The TV ads set the patients up for success . . ." Meridia is effective for weight loss in patients who have no prior experience taking obesity medications, but the success rate in patients with prior anorectic drug use is very poor. The percentage of former obesity medication users is vastly over represented in this survey compared to the general population. Nonetheless, well over 10 million people have taken obesity medications previously, and most of them will not be good candidates for Meridia therapy. Medications that are effective on larger populations of patients need to be developed. Although patients were very upset with the cost of Meridia, as a practical reality, Meridia is no more expensive than other patented prescription medications. But because most patients will pay for both doctors visits and for the medication out-of-pocket, the expense is too great for many. Most patients taking obesity medications will need to take them long term. Meridia is not a practical alternative for patients who cannot afford to spend $100 per month for medication plus the cost of treatment.
Obesity-news is a publication of Hirsch Communications. An on-line subscription is $104.00 per year, payable in advance by check, money order, American Express, VISA or Mastercard. Subscribing is simple using our secure on-line subscription form. Obesity-news also accepts fax orders at 703/960-7462. Copyright 1997-2009, all rights reserved. IMPORTANT: All information in this publication is believed to be accurate and true. Publisher is not liable for omissions or inaccuracies. Information in this newsletter is for educational purposes only and should not be construed as medical advice, or be used in lieu of consultation with a health care provider. |
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