The Promising GLP-1s vs. Human Nature

To catch up on what GLP-1s are all about, please consult the previous post.

Lotte Bjerre Knudsen and Jesper Lau, who are both employees of pharmaceutical giant Novo Nordisk, wrote “The Discovery and Development of Liraglutide and Semaglutide” — and who would be more qualified? The big challenges were to make these substances therapeutically effective for type 2 diabetes patients, and to extend the drug’s half-life.

The action of GLP-1s involves the pancreas, GI tract, heart, lungs, kidneys, liver, thyroid, and brain. This very technical paper takes readers step-by-step through the history of how the researchers figured out a generous plethora of astonishing things about liraglutide and semaglutide. Several weight-loss studies are referenced.

Liraglutide has also been approved as an obesity treatment, and has to be injected daily. Semaglutide is injected weekly, and might soon be available as an oral medication. Why are these substances not already marketed in a form that can be taken by mouth? According to Knudsen and Lau,

Oral absorption of small molecules without enhancers mostly occurs in the intestine, and this has been assumed to be the case for peptide-based drugs with enhancers. However, peptide absorption in the intestine is a challenge, as numerous peptidases may degrade substances before they can be absorbed.

So, the trick is to get the drug absorbed in the stomach, and this might be on the horizon. Liraglutide’s most prevalent side effects are nausea, vomiting, diarrhea, indigestion, and constipation, especially during the up-titration phase. In other words, this is a baby-steps sort of drug, whose dosage is meant to be closely monitored by a doctor.

Other known medical risks include allergic reactions, thyroid cancer, pancreatitis, hypoglycemia, kidney failure, and acute gallbladder disease.

The existence of other drawbacks predicts that liraglutide, as least as an injectable, will not catch on in a big way as a weight-loss drug. Many people will simply not sign up for daily sessions with a hypodermic needle unless it is absolutely, life-savingly necessary.
Cost is of course a huge factor. There are discount programs, but the price hovers around $1,000 for supply that lasts three to five weeks, depending on what the doctor prescribes.

Each year in America, more than 5,000 new cases of T2D diabetes show up in patients younger than 20. Just last June, Victoza (liraglutide’s brand name) was FDA-approved as an injectable for children over 10 who need their blood sugar controlled.

In the trials where liraglutide was verified as promoting weight loss, the result was specifically stated as being in combination with an energy-deficit diet, which for many people is the insurmountable problem. The official language is, “as an adjunct to a reduced-calorie diet and increased physical activity.” More than likely, a large contingent of people would fat-logic themselves into eating more than ever, counting on the medication to erase the extra calories.

Your responses and feedback are welcome!

Source: “The Discovery and Development of Liraglutide and Semaglutide,”, 04/12/19
Source: “FDA Approves Liraglutide for Pediatric Patients with Type 2 Diabetes,”, 06/17/19
Photo credit: Potamos Photography on Visualhunt/CC BY-ND

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OVERWEIGHT: What Kids Say explores the obesity problem from the often-overlooked perspective of children struggling with being overweight.

About Dr. Robert A. Pretlow

Dr. Robert A. Pretlow is a pediatrician and childhood obesity specialist. He has been researching and spreading awareness on the childhood obesity epidemic in the US for more than a decade.
You can contact Dr. Pretlow at:


Dr. Pretlow’s invited presentation at the American Society of Animal Science 2020 Conference
What’s Causing Obesity in Companion Animals and What Can We Do About It

Dr. Pretlow’s invited presentation at the World Obesity Federation 2019 Conference:
Food/Eating Addiction and the Displacement Mechanism

Dr. Pretlow’s Multi-Center Clinical Trial Kick-off Speech 2018:
Obesity: Tackling the Root Cause

Dr. Pretlow’s 2017 Workshop on
Treatment of Obesity Using the Addiction Model

Dr. Pretlow’s invited presentation for
TEC and UNC 2016

Dr. Pretlow’s invited presentation at the 2015 Obesity Summit in London, UK.

Dr. Pretlow’s invited keynote at the 2014 European Childhood Obesity Group Congress in Salzburg, Austria.

Dr. Pretlow’s presentation at the 2013 European Congress on Obesity in Liverpool, UK.

Dr. Pretlow’s presentation at the 2011 International Conference on Childhood Obesity in Lisbon, Portugal.

Dr. Pretlow’s presentation at the 2010 Uniting Against Childhood Obesity Conference in Houston, TX.

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