How Does Ozempic Work? The Mechanism of Action of Semaglutide and Other GLP-1 Receptor Agonists

In early 2023, a type 2 diabetes medication, semaglutide (brand names Ozempic, Rybelsus), drew huge amounts of attention on social media and in popular culture. The reason? People were getting off-label (that is, not for treating type 2 diabetes) prescriptions of Ozempic to take advantage of one of its common side effects—measurable weight loss.

How does semaglutide and other drugs of its type manage diabetes on a molecular level, and what drives the weight loss effects?

Female leg stepping onto a weigh scale
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Battling Obesity One Thermostat at a Time

ThermometerWinter in Wisconsin is synonymous with cold, and this year thanks to the “wobbly polar vortex” it has been really, really cold. I have been very grateful for my under-desk space heater at work and my toasty gas fireplace at home. However, according to an article currently in press in the journal Trends in Endocrinology and Metabolism (1), all that lovely toasty warmness might be working against me if I am hoping to loose weight.

Excess weight is nothing more than a positive energy balance, meaning we have taken in more calories than we have burned. The deceptively simple sounding solution for losing or maintaining weight is to take in no more calories than you will be expending. Typically this is achieved by eating less, increasing physical activity or through pharmacological interventions. However, anyone who has ever tried any of these approaches knows that there is nothing simple about them, and often times the results are disappointing or short lived.

The authors of the Trends in Endocrinology and Metabolism paper hypothesize that regular exposure to mild cold could affect our energy expenditure in a positive way. We know that shivering produces heat (shivering thermogenesis) and thus expends energy. It can increase the metabolic rate to up to five  times the resting rate (2). However, it is not comfortable and can make coordinated movements difficult. The authors focused on something close to this state, but not quite. Nonshivering thermogenesis (NST) is the cold-induced increase in heat production that is does not involve muscle activity like shivering. It occurs by activating brown adipose tissue (3–5).

Although there is great variation between individuals, most young and middle-aged people will see an increase in NST between a few percent to up to 30% when exposed to mildly cold conditions (1). The authors note that a recent study found a significant decrease in body fat content following a 6 week cold acclimation study (2 hours/day at 62.6°F [17°C]; 6).

ScaleAs many of us can probably attest, the downfall of undertaking anything that increases our body’s energy usage is that often we end up increasing our caloric intake to compensate for it. Interestingly, the authors point to a 2009 study (7) that found evidence that increased food intake did not fully compensate for this type of cold-induced thermogenesis.

Personally, I love to be warm— as evidenced by my previous comments about space heaters and gas fireplaces. However, if the benefits of cold acclimation suggested by this paper hold to be true, I think I could tolerate 2 hours a day at 62°C.


  1. Van Marken Lichtenbelt. W. et al. (2014) Cold exposure—An approach to increasing energy expenditure in humans. Trends Endrochron. Met. In Press.
  2. Jansky, L. (1998) Shivering. In Physiology and Pathophysiology of Temperature Regulation (Blattheis, C.M. ed.) World Sceintific.
  3. Cannon, B. and Nedergaard, J. (2004) Brown adipose tissue: Function and physiological significance. Physiol. Rev. 84, 277–359.
  4. Van Marken Lichtenbelt, W.D. et al. (2009) Cold-activated brown adipose tissue in health adult men. N. Engl. J. Med. 360, 1500–1508.
  5. Virtanen, K.A. et al. (2009) Functional brown adipose tissue in health adults. N. Engl. J. Med. 360, 1518–1525.
  6. Yoneshiro, T.  et al. (2013) Recruited brown adipose tissue as an antiobesity agent in humans. J. Clin. Invest. 123, 3404–3408.
  7. Cannon, B. and Nedergaard, J. (2009) Thermogenesis challenges the adipostat hypothesis for body-weight control. Proc. Nutr. Soc. 68, 401–407.

The Buzz About Akkermansia muciniphila: It’s More Than Just Weight Loss

ScaleThe bacterium Akkermansia muciniphila is creating quite a stir in science news, with people calling it the “weight loss bacterium”. While it’s exciting to think about a bacterium that has the ability to reduce body weight with no change in food intake, there’s another reason to get excited: The potential to treat obesity-related metabolic disorders such as type-2 diabetes and perhaps even diseases related to intestinal inflammation.

There are hundreds of bacterial species that colonize the gut. Why has this bacterium been dubbed the “weight loss bacterium”, and why do researchers have such lofty goals for this simple unicellular organism? Continue reading “The Buzz About Akkermansia muciniphila: It’s More Than Just Weight Loss”

Lard: It Does a Body Good!

Walking through the grocery store, one can’t help but see the campaign against fat: low-fat yogurt, fat-free salad dressing and skim milk all play their roles. There are even fake-fat potato chips out there. From fat burners to fat blockers, it seems like fat, and especially saturated fat, is Public Enemy #1.

Most anti-fat crusaders state that it is not the monounsaturated or polyunsaturated fat that is the problem; rather, the fault lies with our consumption of saturated fat. They consistently recommend eating foods that are high in the unsaturated fats, such as fish and olive oil, and avoiding saturated fat-laden foods like butter, pork, lard and coconut oil. While they may even agree that all fats are healthy, they also recommend that such “healthy” fats should constitute no more than 7–11% of our total calorie intake.

However, what is the real story behind saturated and other fat? Is fat really the weight-enhancing, heart disease-inducing, artery-clogging, cancer-causing, acne-generating villain we make it out to be? Will it ruin your health? Frankly, is fat really bad for you? Continue reading “Lard: It Does a Body Good!”

Sleeping Away the Inches

Back at the beginning of the year, a great many of us resolved that we would lose some weight in 2010. Some of us vowed we would get up early, sacrificing an hour or two of sleep to squeeze in an hour or so of exercise before the rest of our busy schedule hijacked our day. What we didn’t realize was that we may have sabotaged our efforts to lose what we wanted to get rid of –fat– by giving up something our body wanted –sleep.

Sleeping woman in bed

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