The Drugs don’t Work. Or do They?
The PROs and CONS of Prescription Weight Loss Medications
World Obesity Day is on October 11, and it is a timely reminder of the obesity epidemic. Treatment is challenging. Lifestyle modifications work but benefits are often modest and they can be difficult to maintain. Bariatric and metabolic surgery is very effective but comes at a high cost and significant risk so is limited to those with the most severe obesity. This leaves a considerable unmet need for millions of obese and overweight people. Pharmacotherapy could meet this need. The US Preventive Services Task Force (USPSTF) has recently released a review and a statement recommending that pharmacotherapy can increase weight loss but also harm.1,2 No surprises there – almost every medication that is effective comes at the expense of side effects. So, are the currently available prescription weight loss medications really worth it?
Considering this, two of our obesity experts here at DRG have decided to take a closer look at the pros and cons of prescription weight loss medications.
PROs of Obesity Medications
Andrew Frost – Business Insights Analyst
Everybody has to start somewhere; although the obesity space may have not had the most auspicious start, there are some positives to have come from the availability of weight loss medications across the G7 markets.
More treatments = more treatment
As we have seen with other metabolic indications, most notably with NASH, a lack of approved therapies is a major reason cited by physicians for low diagnosis and treatment rates, especially in primary care – in Japan, where there is only one treatment approved for the treatment of obesity (compared to six in the USA), drug treatment rate estimates are extremely low. DRG forecasts that the increased availability of current and novel weight loss medications over the next decade will increase visibility of obesity across the G7, leading to (albeit modest) rises in diagnosis and treatment rates.3
Prescription medicines reflect weight of disease
The theme of the 2018 World Obesity Day is Ending Weight Stigma, defined as “negative behaviors and attitudes that are directed towards individuals solely because of their weight”. Despite a number of countries (including the USA and Canada) officially classifying obesity as a disease, the view that it is a lifestyle choice rather than an illness remains amongst the general population and even physicians. The continued availability of pharmacotherapies for obesity will likely help to shift the view that obesity is not simply a lifestyle choice, but rather a complex metabolic disorder that requires treatment.
Reduce weight, reduced risks
Patients with obesity frequently present with other comorbidities e.g. type 2 diabetes, NASH, dyslipidemia, heart disease etc.). In addition to pharmacotherapy, continued evidence shows that weight loss alone is able to ameliorate or even completely resolve these comorbid indications.4,5 Novo Nordisk’s liraglutide (Saxenda) and semaglutide, have both been shown to reduce cardiovascular risk6,7 and to have efficacy in the treatment of NASH (although it is unclear if this effect is mediated via weight loss or an additional off-target GLP-1 related effect). In Eisai’s CAMELLIA-TIMI CVOT trial, in addition to showing no additional CV risk, treatment with lorcaserin was shown to decrease risk for incident diabetes and to reduce microvascular complications associated with diabetes.8 Any drug that facilitates weight loss, leading to improvement in associated metabolic indications can surely not be a bad thing?
Although it must be said that the current options for weight loss therapy do leave a lot to be desired, this is, effectively, the first generation of treatments for this disease. As our understanding in this complex metabolic disease increases, it’s likely that the efficacy and benefits offered by future therapies will follow suit. Thankfully, the early clinical data for novel treatments on the horizon offer hope of bridging the gap between unappealing diet and exercise routines and the surgeons’ knife.
CONs of Obesity Medications
Tim Blackstock – Director
They say, “every little bit helps” but I am not sure that in the case of weight loss medications this rings true. None of the drug treatments for obesity on the US market are widely prescribed and there are numerous reasons why.
Short but not so sweet
Phentermine – the go-to drug for many physicians – can only be prescribed for 3 months. Moreover, it provides limited weight loss and is not recommended for use in patients with CV disease.
Eisai’s Belviq (lorcaserin) has recently been shown to not increase CV risk in patients. This is of course a positive, which is useful because the weight loss it offers is modest. Unfortunately, neuropsychiatric side effects were reported more commonly in Belviq-treated patients that placebo-treated patients in clinical trials.
Efficacious but not effective?
In contrast, Vivus’s Qsymia (phentermine/topiramate) has the best efficacy of any available agent but a CV safety trial requested by the FDA has not been completed after more than 5 years on the market. Moreover, the topiramate component come with the added bonus of possible birth defects.
Contrave/Mysimba (naltrexone bupropion) had more promise, seemingly safer than Qsymia and more effective than Belviq and quickly becoming the banded agent of choice after launch. However, sales leveled off and two attempts at CV outcomes trials were terminated followed by the developer Orexigen going bankrupt.
Weighing up the price
Saxenda (liraglutide 3 mg), from pharma giant Novo Nordisk, delivers moderate weight loss and possibly even CV benefits based on studies of liraglutide in diabetics. However, it is a daily injectable that costs a lot.
Last but not least is Xenical. This relatively expensive drug has been on the market for almost 20 years but has not met with any generic competition. This may be because although it is safe, it has modest efficacy, comes with a burdensome dosing regimen and some rather unpleased gastrointestinal side effects. Oily spotting anyone?
However, perhaps the most damning evidence is that many of these treatments have failed to be approved or even submitted for evaluation by regulators in Europe or Japan.
In summary, despite the high unmet need there is no safe, effective, convenient, well tolerated, affordable, long-term weight loss therapy on the U.S. market. Patients are often paying a lot of money for drugs that even if they work do not provide any noticeable change in their appearance or even weight or while experience unpleasant side effects. Five percent weight loss after a year is the threshold of efficacy set by the FDA. But if you weight 440lb (200 Kg) and lose 5% you now way 418lb (190kg). Your cardiovascular disease risk might have improved but after a year’s worth of side effects and the cost of replacement underwear you would not even notice any difference in the mirror.
What is your opinion on obesity pharmacotherapy? Please leave a comment.
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- LeBlanc ES, et al. Behavioral and Pharmacotherapy Weight Loss Interventions to Prevent Obesity-Related Morbidity and Mortality in Adults – Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. 2018;320(11):1163-1171.
- US Preventive Services Task Force. Behavioral Weight Loss Interventions to Prevent Obesity-Related Morbidity and Mortality in Adults – US Preventive Services Task Force Recommendation Statement. JAMA. 2018;320(11):1163-1171.
- Decision Resources Group. Obesity: Disease Landscape and Forecast. October 2017.
- Lean ME et al. Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. 2018 Feb 10;391(10120):541-551.
- Vilar-Gomez E et al. Weight Loss Through Lifestyle Modification Significantly Reduces Features of Nonalcoholic Steatohepatitis. 2015 Aug;149(2):367-78.
- Marso SP et al. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med 2016; 375:311-322.
- Marso SP et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2016 Nov 10;375(19):1834-1844.
- Bohula EA et al. Effect of lorcaserin on prevention and remission of type 2 diabetes in overweight and obese patients (CAMELLIA-TIMI 61): a randomised, placebo-controlled trial. Lancet. 2018 Oct 3. pii: S0140-6736(18)32328-6.