Sunday, November 26, 2023

Weight loss drugs - are they for me?

Last year, Denmark published statistics on its Gross Domestic Product with and without Novo Nordisk, the giant Danish pharmaceutical company that markets Wegovy – that is how much money is rolling in to the manufacturer of the wildly successful obesity drug.

Why are Wegovy and friends such a hit? What should you know about these drugs?

America is suffering an epidemic of overweight and obesity – some 70% of us are either overweight (BMI>27) or obese (>30). Excess weight contributes to the development of hypertension, diabetes and heart disease and losing 5% or more of body weight has been demonstrated to lower the risk of cardiovascular disease.

The problem is that losing weight is hard. For most of us it goes well beyond “will power.” The determinants of weight are complex, and include genetics, environment and habits. The food industry with its high fructose additives and advertising are also culprits.

Enter the holy grail – the search for a safe and effective drug that will help people lose weight.

Drugs for weight loss have been around for a while, and include phentermine, orlistat and Contrave.

Phentermine is an amphetamine that has been shown to produce about 6% of body weight loss after 6 months of use, but has the expected side effects of anxiety, racing heart and insomnia. Orlistat decreases the body’s absorption of fat and leads to about a 5% weight loss; it has a number of bowel side effects including leaking of stool, though is otherwise safe. Contrave combines naltrexone, an opioid blocker, and bupropion, an antidepressant. About half of those using it lose at least 5% of body weight after a year. Side effects include seizures, behavior changes and suicidal thoughts.

So, modest weight loss and serious or annoying side effects with these older agents.

The new kids on the block are GLP-1 agonists – drugs that mimic the effects of glucagon-like-peptide-1. They send a signal to the brain that you are full and also slow the stomach emptying. These drugs have been used to treat diabetes since 2005. Because they must be injected, they never captured much of the diabetes market.

What has turned the GLP-1 agonists into blockbusters is their dramatic effects on weight. In different trials with different products, subjects lost 12-20% of their body weight after a year. Most recently, a trial of semaglutide in very high-risk patients – in their 60’s with established cardiovascular disease – showed that those on the drug had 20% fewer events (heart attack, stroke or cardiovascular death).

There are now three products on the market: Wegovy (semaglutide), Saxenda (liraglutide) and Zepbound (tirzepatide – a GLP-1 agonist plus another). Given the vast market potential, more will follow.

What is the downside? First is cost. Wegovy retails for $1349/4 weeks; Zepbound for $1060/4 weeks; Saxenda about $1300/4 weeks. And note that these drugs must be taken indefinitely! In trials, those who stopped the drug after a year regained most of the weight they had lost by a year after stopping.

Nuisance side effects including nausea, diarrhea and constipation are common. More serious side effects including inflammation of the pancreas or gallbladder, kidney injury and suicidal thoughts have been reported in less that 1% of people taking them.

Are they for you? If you are seriously overweight and have other conditions such as diabetes, high blood pressure and/or heart disease, and if you have made your best effort at losing weight without medication, definitely discuss their use with your doctor.

Remember that weight is a life-long issue, and commit to using dietary changes and exercise as part of your life.

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  1. I hope it's okay to put this in your comments, since it may be idiosyncratic results, but I have found a simple and very effective diet: don't eat lunch. I eat a very light breakfast as well (large latte and a handful of almonds), but I think the real caloric drop comes from skipping lunch altogether. If you're like me, you'll get urges and thoughts like ("But if I don't eat, I'll be weak!"). All I do is firmly recognize that these are erroneous thoughts, and that I can eat all I want at dinner. I even have heavy ice-cream desserts at dinner. On this regimen, I lost 30 pounds in 3 to 4 months. I've been on it for a year, and am not tempted to go back to eating lunch. I do drink a lot of Diet Coke throughout the day. Your mileage may vary.

  2. Follow-up: that 30 lbs. was from 180 to 150, so it's 16 2/3 %.

  3. Intermittent fasting works for many people, and this is a variation on that theme. Whatever works!