So, I have conversations about diet, exercise and weight loss every day in my practice. But it seems that sometime around Jan 1, those conversations are more often started by my patients. We are moving from the indulgent end of the year holiday season, to the fresh start of a new year. So it seems natural to try to start fresh- live healthier, better, richer…
Well, maybe not richer. But there are a lot of people getting richer of our desires to look and feel healthier. So there are a lot of theories about how we got her, and promises to do this one thing, cut out this, take this pill, and turn your life around. Face it, a quick fix seems pretty damn appealing to all of us. And I am in the pill pushing business. A big part of my job is to prescribe medicines. So with all of these conversations about losing weight, medicine is a frequent question.
So today, I’m going to build on a recent morning report lecture on obesity to focus on medical treatments for obesity. We’ll talk about old, new, tried and true and up and coming. I’ll try to highlight the evidence base for these so that you can discuss in an informed way with your patients.
I also want to start with a disclosure.. I almost never prescribe medicine for weight loss. My bias (and I’ll argue, the evidence) is that these are generally not that helpful, and almost always patients gain back weight, plus more, once they stop taking them. The studies that got these medicines approved were always coupled with a solid diet and exercise plan, and I think that most of the weight loss comes from that activity, NOT from the medicine.
Orlistat inhibits pancreatic lipases, so less fat is absorbed in digestion. In studies, patients on orlistat lost 5-10kg (compared to 3-6kg with diet/exercise alone). It also has been shown to lower blood pressure, and LDL levels more than would be expected by the weight loss alone. It is safe, as most of it remains un-absorbed. However, the main side effects are GI related: bloating, nausea, and diarrhea. These are generally pretty limiting, and I haven’t found many patients willing to even try orlistat after hearing these effects. However, if patients can stick to a low-fat diet, the effects can be minimized.
Phentermine is a stimulant that suppresses appetite. It is the oldest of the approved medicines for weight loss, and also one of the cheapest. It is approved for 12 weeks of therapy, so most studies are of short duration only. Studies show around 7kg of weight loss. Side effects include hypertension, tachycardia, anxiety, insomnia- in my experience these are pretty limiting.
There is a new medicine that combines phentermine with topiramate, Qsymia. The phentermine dose is lower than if prescribed separately, and it is approved for longer term use. The initial trial for this Rx showed patients lost 8-10 kg in the first year, and could maintain weight loss if they continued for another year. Only about 60% of patients took the Rx for the whole first year.
So what about just Topiramate itself? Currently topiramate is approved for treatment of epilepsy and migraine. Using it for weight loss is off label- so beware. However, it has been studied, and patients lost about 4kg over 6 months in the various trials.
Lorcaserin (Belviq) is a serotonin receptor agonist, and thus serves as an appetite suppressant. A few other serotonin agonists have been tried over the years- fenfluramine- and lead to cardiac valve disease. Lorcaserin is more specific to the 2C receptor, which should minimize cardiovascular effect. In trials, more patients on lorcaserin lost at least 5% of their body weight (mean 5kg). There were also decreases in BP, HR, LDL, CRP, and glucose. All of the trials had dropout rates close to 50%. Side effects include headache, nausea, URI sx, and back pain.
Liraglutide (Victoza, Saxenda- same Rx, two brand names) is the one drug in this group with an indication for weight loss. In patients without diabetes, trials showed around 7kg of weight loss, and in one trial, patients who lost weight pre medicine were more likely to maintain the weight loss if on liraglutide. Side effects include nausea/vomiting/diarrhea and rarely, pancreatitis.
Metformin Old drug, lots of data on weight loss, but still no indication for obesity treatment. Why? Patients don’t tend to lose a lot of weight with metformin- about 2kg. But what different with metformin, is that there is long-term data that showed that patients could maintain that weight loss as long as they stayed on the Rx. And it decreases incidence of diabetes in these people as well. Certainly something to consider in obese patients with pre-diabetes or otherwise at high risk.
Another off label use here, but post marking data did show a tendency toward weight loss in patients on bupropion. Remember, this drug increases norepinephrine effect, so likely has some sympathomimetic benefits. In one short (6 month) trial, patients on bupropion lost 7-10% of their body weight (compared to 5% lost on placebo).
There is a brand new combo drug that uses Naltrexone and Bupropion (Contrave). Patients got about 5% weight loss over a longer study (56 weeks), but only about half of the patients were able to complete the study. Nausea, headache, and constipation were common side effects. There is also a cardiovascular concern that is being actively monitored in the post-marketing period.
Diet and exercise are the key- slow and steady wins the race. There may be some small incremental gains with the medicines above, but I think that the evidence is thin, there are clear side effects, and the risks are not always understood. Given the millions of Americans that could end up on these medicines, I’d prefer to hang back and wait for the fallout before becoming an early prescriber of any of these.