The latest news from the Food and Drug Administration is the approval of the drug tirzepatide for weight loss. We have no comment on the brand name Zepbound. While we don’t find this trade name particularly catchy, I suspect that the company, Eli Lilly, spent a bundle coming up with that label. What’s the skinny on the latest diabetes drug to get a green light for weight loss? Is Zepbound better than Wegovy when it comes to shedding pounds? What about side effects and cost?
A REALLY Short History of GLP-1 Agonists Against Diabetes and Obesity!
On November 8, 2023 the FDA approved Zepbound (tirzepatide) injections for the treatment of obesity. We saw this day coming back on August 3, 2023. That’s when we wrote an article titled:
Give me a moment to provide a short history of GLP-1 agonists. It’s not as boring as you might think.
The snowball started coming down the mountain back on April 28, 2005. That’s when the FDA approved exenatide (Byetta) to help control blood sugar.
On January 25, 2010, the injected drug liraglutide (Victoza) was also approved by the FDA for the treatment of type 2 diabetes. It too was a GLP-1 (glucagon-like peptide 1) agonist approved to control blood sugar.
The same medication got the FDA’s green light for weight loss in December, 2014. The brand name was Saxenda. You can read more about this injectable medication and how well it worked at this link. Saxenda has to be injected daily. At the end of a year people lost about 12 pounds more than those getting placebo injections.
In December, 2017, the FDA approved another GLP-1 agonist for the treatment of type 2 diabetes. The self-injectable drug semaglutide (Ozempic) was longer-acting than liraglutide. Instead of a daily shot, people could inject Ozempic once weekly.
This drug also got a green light for weight loss, but not until June 4, 2021. Novo Nordisk gave semaglutide a shiny new name for weight loss. The new name was Wegovy when doctors prescribed it for obesity treatment. The snowball that started down the mountain so many years ago started picking up momentum!
It wasn’t until social media and Elon Musk that semaglutide injections really took off. You can read about that phenomenon at this link.
The FDA approved tirzepatide injections for the treatment of type 2 diabetes on May 13, 2022. The brand name was Mounjaro. It “activates” two receptors. The first is the old familiar GLP-1 (glucagon-like peptide 1). The second is a mouthful: glucose-dependent insulinotropic polypeptide (GIP). The goal of this dual-action, once-weekly injectable drug: improved blood sugar control. There are three different doses (5 milligrams, 10 mg and 15 mg).
On November 8, 2023 the FDA announced the approval of tirzepatide injections for:
“…chronic weight management in adults with obesity (body mass index of 30 kilograms per square meter (kg/ m2) or greater) or overweight (body mass index of 27 kg/m2 or greater) with at least one weight-related condition (such as high blood pressure, type 2 diabetes or high cholesterol) for use, in addition to a reduced calorie diet and increased physical activity.”
Tirzepatide for Diabetes AND Weight Loss:
We first wrote about tirzepatide (Zepbound) for weight loss on August 3, 2023. The title of that article was:
We were reporting on a press release from Eli Lilly. The drug company was reporting on the results of two clinical trials (SURMOUNT-3 and SURMOUNT-4) about tirzepatide for weight loss.
Here is what the company reported:
“Participants in SURMOUNT-3, after 12 weeks of intensive lifestyle intervention, achieved an additional 21.1% mean weight loss with tirzepatide for a total mean weight loss of 26.6% from study entry over 84 weeks
“Participants in SURMOUNT-4 achieved 21.1% weight loss during a 36-week tirzepatide lead-in period and an additional 6.7% weight loss during a 52-week continued treatment period, for a total mean weight loss of 26.0% over 88 weeks.”
How Does Zepbound Compare to Wegovy?
First, we rarely see head-to-head clinical trials of pharmaceuticals. Drug companies seem reluctant to test their brand name babies against competing medications. So, we cannot answer the question posed above in a perfectly scientific manner. To do so would require the exact same protocol for the drugs in question. Ideally, it would be carried out by a third party that had no financial interest in the outcome.
What we can say is that the FDA wrote this about Wegovy on June 4, 2021:
“The largest placebo-controlled trial enrolled adults without diabetes. The average age at the start of the trial was 46 years and 74% of patients were female. The average body weight was 231 pounds (105 kg) and average BMI was 38 kg/m2. Individuals who received Wegovy lost an average of 12.4% of their initial body weight compared to individuals who received placebo. Another trial enrolled adults with type 2 diabetes. The average age was 55 years and 51% were female. The average body weight was 220 pounds (100 kg) and average BMI was 36 kg/m2. In this trial, individuals who received Wegovy lost 6.2% of their initial body weight compared to those who received placebo.”
“The larger of the two trials enrolled adults without diabetes. At the start of the trial, the average body weight was 231 pounds (105 kg) and average body mass index was 38 kg/m2. In this trial, those randomized to receive the highest approved dosage of Zepbound (15 mg once weekly) lost on average 18% of their body weight compared to those randomized to placebo.
“At the start of the trial in adults with type 2 diabetes, the average body weight was 222 pounds (101 kg) and average body mass index was 36 kg/m2. Those randomized to receive the highest approved dosage of Zepbound (15 mg once weekly) lost on average 12% of their body weight compared to those randomized to placebo.”
Relying on the FDA’s spin, it would appear that Wegovy helped overweight patients lose between 6.2% and 12.4% of their initial body weight compared to those on placebo. The agency reports that those on Zepbound lost 12% to 18% of their initial body weight compared to people getting placebo.
Eli Lilly Spins Zepbound Even More:
In its press release the drug company goes farther than the FDA in promoting Zepbound:
“Additionally, 1 in 3 patients taking Zepbound at the highest dose lost over 58 lb. (25% of body weight), compared to 1.5% on placebo, according to data not controlled for type 1 error. The average starting weight was 231 lb.”
Is Zepbound Safer Than Wegovy?
We are not ready to reach that conclusion. Here is what the drug company states in its press release.
“Warnings – Zepbound may cause tumors in the thyroid, including thyroid cancer. Watch for possible symptoms, such as a lump or swelling in the neck, hoarseness, trouble swallowing, or shortness of breath. If you have any of these symptoms, tell your healthcare provider.
“• Do not use Zepbound if you or any of your family have ever had a type of thyroid cancer called medullary thyroid carcinoma (MTC).
• Do not use Zepbound if you have Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
• Do not use Zepbound if you have had a serious allergic reaction to tirzepatide or any of the ingredients in Zepbound.
“Zepbound may cause serious side effects, including:
Severe stomach problems. Stomach problems, sometimes severe, have been reported in people who use Zepbound. Tell your healthcare provider if you have stomach problems that are severe or will not go away.
Kidney problems (kidney failure). Diarrhea, nausea, and vomiting may cause a loss of fluids (dehydration), which may cause kidney problems. It is important for you to drink fluids to help reduce your chance of dehydration.
Gallbladder problems. Gallbladder problems have happened in some people who use Zepbound. Tell your healthcare provider right away if you get symptoms of gallbladder problems, which may include pain in your upper stomach (abdomen), fever, yellowing of skin or eyes (jaundice), or clay-colored stools.
Inflammation of the pancreas (pancreatitis). Stop using Zepbound and call your healthcare provider right away if you have severe pain in your stomach area (abdomen) that will not go away, with or without vomiting. You may feel the pain from your abdomen to your back.
Serious allergic reactions. Stop using Zepbound and get medical help right away if you have any symptoms of a serious allergic reaction, including swelling of your face, lips, tongue or throat, problems breathing or swallowing, severe rash or itching, fainting or feeling dizzy, or very rapid heartbeat.
Low blood sugar (hypoglycemia). Your risk for getting low blood sugar may be higher if you use Zepbound with medicines that can cause low blood sugar, such as a sulfonylurea or insulin. Signs and symptoms of low blood sugar may include dizziness or light-headedness, sweating, confusion or drowsiness, headache, blurred vision, slurred speech, shakiness, fast heartbeat, anxiety, irritability, mood changes, hunger, weakness or feeling jittery.
Changes in vision in patients with type 2 diabetes. Tell your healthcare provider if you have changes in vision during treatment with Zepbound.
Depression or thoughts of suicide. You should pay attention to changes in your mood, behaviors, feelings or thoughts. Call your healthcare provider right away if you have any mental changes that are new, worse, or worry you.
Common side effects
The most common side effects of Zepbound include nausea, diarrhea, vomiting, constipation, stomach (abdominal) pain, indigestion, injection site reactions, feeling tired, allergic reactions, belching, hair loss, and heartburn. These are not all the possible side effects of Zepbound. Talk to your healthcare provider about any side effect that bothers you or doesn’t go away.
Tell your healthcare provider if you have any side effects. You can report side effects at 1-800-FDA-1088 or www.fda.gov/medwatch.”
Final Words about Zepbound:
Did your eyes glaze over about one tenth of the way down that list of side effects and warnings? It is easy to feel overwhelmed when faced with so many side effects. Drug companies seem more than willing to list a lot of potential adverse reactions. I will not attribute motives to such long lists…but I suspect that many people zone out after reading about things like “Multiple Endocrine Neoplasia syndrome type 2, medullary thyroid carcinoma, swelling of your face, lips, tongue, or stomach problems that are severe or will not go away.”
There may be one other reason for such long lists of side effects. If people are warned about possible adverse drug reactions in advance, they have a very hard time suing for damages if they suffer complications. As long as a pharmaceutical manufacturer warns about problems such as nausea, vomiting, diarrhea or death, it is hard to win a lawsuit. Read about this at this link.
What About Cost?
These drugs are pricey! According to Eli Lilly, Zepbound will cost around $1,000 for a month’s supply. That’s less than the list price of Wegovy, which is around $1,300 a month. Insurance companies may pay, but many people will have to meet pretty strict conditions to qualify.
Let’s be honest, drug companies are going to make a lot of money on GLP-1 and GIP agonists. Wegovy, Ozempic and Mounjaro have been in short supply because of the demand, despite the price.
Would you like a balanced perspective on the GLP-1 agonists like Wegovy and Zepbound? We recently interviewed two experts on obesity. We think it is worth spending a little time listening to our two-part series:
The Lowdown on New Medicines for Treating Obesity:
Show 1361: The Lowdown on New Medicines for Treating Obesity
Prescribing new medicines for treating obesity has let our guest help many patients unable to lose weight by other means.
Show 1362: Lowdown on New Medicines for Treating Obesity –Part 2
In this episode, we consider the benefits and considerable risks of drugs like Wegovy for treating obesity. Our guest says eat real food!
What do you think? Please share your thoughts about the “new” weight loss drugs in the comment section below. When you see the green box that states “View Comments,” please click. That will provide you with a sidebar listing Comments. You can add your thoughts in the box that says “Add your comment.” Thank you.