Close Concerns: Weight Loss and Weight Loss-Maintenance

Earlier this week, the influential healthcare information firm Close Concerns published a rather lengthy interview regarding my take on a wide range of issues related to the future of obesity management. The interviews were conducted by Joseph Shivers, Vincent Wu, Lisa Vance, and Kelly Close, who certainly challenged and stimulated my thinking with their well-informed questions.

The following is another brief excerpt from this interview published in their newsletter Closer Look:

JOSEPH: The prospect of long-term weight loss in the population as a whole seems very challenging based on most interventions for which we have long-term data. Assuming that we turn this around in the next 50 years, what do the turning points have to be? Will it be better therapy? Some really refined and effective surgery? Impacting childhood obesity?

DR. SHARMA: If I had to bet, I’d bet on drugs and not on surgery. I think surgery is a phase. It’s being done now; it’ll be around for probably another decade or so, maybe longer, until we get new drugs. I think that there are two things that may need to change in drug development, or even in the thinking about pharmacological treatment of obesity.

The first is starting to differentiate obese people into subsets of obese people. So a drug that doesn’t have to be for whoever has obesity, but rather for a subset of patients with obesity because they have a certain eating disorder or there’s a certain pathway in their brains that is promoting overeating or they have a certain lack of satiety. That is a group of patients for whom a given drug really works. They are the ones who should be getting it. The drug may not work for everybody else. You would start splitting down this whole indication into other groups.

That may or may not happen. In hypertension it never happened. We have 100 drugs for hypertension and people have always said, “Let’s break it down and let’s decide who’s the best patient for a diuretic and who’s the best patient for a beta blocker and who’s the best patient for an ACE inhibitor.” That actually never worked. In the end, even today, hypertension practice is pretty much trial and error, with fixed combinations becoming more and more accepted.

So, I’m not holding my breath that that will happen with obesity. I think if you find drugs that are overall effective and well tolerated in most people or at least half the people you treat with them, it probably doesn’t matter.

But I think the other piece that really matters is whether or not we can come up with a way to license drugs to help with weight-loss maintenance. The mechanisms that help you lose weight may not be the same mechanisms that help you keep weight off. Take leptin, for example. Leptin is not a great drug for losing weight, but it may be the perfect drug to keep weight off. But there’s no pathway. If I wanted to license leptin for weight management, I would have to go to the FDA and show that it helps people lose weight, which it doesn’t, and so I’d never be able to license it. I need a pathway that’s going to allow me to specifically get regulators to approve a drug that is efficacious for helping people maintain weight loss, even if it does not promote weight loss in itself.

So, the idea is you go lose weight and come back to the doctor’s office, and then he’ll put you on these drugs so that your weight doesn’t come back. That is a regulatory pathway that doesn’t exist right now.

JOSEPH: It seems like the standard of care for weight-loss, excluding drugs and devices in some patients, is intense diet and exercise as a starting point. What do you think about this approach?

DR. SHARMA: It’s simply not going to work. All that diet and exercise talk is like what we used to do for cholesterol and for diabetes. I’m not saying it’s not important, and there’s no question that if I get somebody to diet and exercise, they’ll lose weight. But it works for obesity in the same way that the DASH [Dietary Approaches to Stop Hypertension] diet works for hypertension. I can put people on the DASH diet and show that their blood pressure gets better. But if I were to take 100 people off the street, put them all on the DASH diet, and hope that everybody’s blood pressure’s going to be fine, it won’t be. Only five guys would actually stick to the diet, and they’d be fine, but the other 95 would not be fine. Obesity is pretty much the same; I don’t see any difference at all.

KELLY: Presumably weight-loss maintenance also goes back to improving the public’s understanding of obesity and addressing weight bias and discrimination.

DR. SHARMA: Absolutely, we are bombarded with anecdotal instances of how easy it is to lose vast amounts of weight – not just the ‘weight-loss industry’ – think of TV reality shows, popular magazines, and fad diets. We celebrate people for losing weight – we seldom check to see if they are still keeping it off. I am always asked by patients, “How much weight can I lose and how fast can I lose it?” I tell them that that’s the wrong question – the only weight loss that matters is the weight you can keep off – this is why we introduced the term ‘best weight’ – the lowest weight you can realistically maintain. Your ‘best weight’ depends on your individual circumstances – everyone’s ‘best weight’ will be different.

The public but also health professionals and policy makers need to understand that when you pay for ‘weight loss’ you get ‘weight loss’ – when you pay for ‘maintenance of weight loss’ you get ‘maintenance of weight loss’. As a health professional I’d rather see my patients or payors paying for the latter than the former.

Another point is that we often frame weight regain as ‘failure’ when it is really the only natural expected consequence of stopping the treatment for a chronic condition. Even worse, the failure is often framed in the context of the treatment. So if you take a drug – lose weight – stop the drug- regain the weight – we attribute the failure to the drug and not to ‘stopping’ the drug. No drug or treatment works when you don’t take it – when you have an obesity treatment that works, the question is not to find more effective weight loss drugs but to find a more effective way of ensuring that people continue taking it.

The same, incidentally, applies to treatments for hypertension or diabetes. For many conditions we don’t need more drugs (unlike for obesity) – we simply need to figure out how to get patients to continue taking the meds that are already out there – that’s where I’d be putting most of my research money.

To be continued….

London, UK