Is Mounjaro Safe For Weight Loss? What You Need To Know
This blog explores how Mounjaro works and outlines possible side effects and potential risks to help you make informed choices.
What is Mounjaro, and What’s All The Buzz About?
Tirzepatide is an anti-diabetic and weight-loss medication sold under the brand names Mounjaro for diabetes and Zepbound for weight loss. Tirzepatide (the generic name for the medication) is a dual-peptide medication (compared to Ozempic, which has only a single peptide - GLP1). Its two peptide hormones are:
Gastric inhibitory polypeptide (GIP)
Glucagon-like peptide (GLP-1) receptor agonist
Originally developed to treat diabetes, tirzepatide keeps blood sugar low by stimulating insulin secretion and slowing glucagon release. This effect on blood sugar facilitates lipolysis (i.e., fat-burning). Mounjaro received FDA approval in 2022, and Zepbound, the drug specifically approved by the FDA to treat obesity, in 2023. Similar to semaglutide (Ozempic), research conducted on tirzepatide resulted in an incidental finding that the medication causes significant weight loss.
How Does Terzepatide Work? GLP-1 Receptor Activation and GIP Receptor Activation Effects
Increases Insulin Secretion in a Glucose-Dependent Manner
This means that insulin is only released in the presence of glucose and prevents excessive insulin levels.
Suppresses glucagon release, reducing blood sugar levels.
Enhances insulin secretion from pancreatic beta cells.
It may improve fat metabolism and increase energy expenditure.
By acting on both GIP and GLP receptors, tirzepatide enhances blood sugar control by promoting weight loss through appetite suppression and metabolic effects.
Suppresses Glucagon
Glucagon is a hormone that increases blood sugar levels and prevents them from dropping too low by prompting the liver to release stored glucose.
Too much glucagon can lead to insulin spikes and fat storage.
Some people with type 2 diabetes have higher than normal levels of glucagon.
Tirzepatide helps balance insulin and glucagon levels.
This improved ratio of insulin and glucagon facilitates the use of stored fat more efficiently.
Promotes Satiety Hormones
Peptide YY: GLP-1 enhances PYY secretion, which promotes satiety and reduces food intake
Leptin: Overweight or obese patients often develop an insensitivity to leptin. Leptin regulates hunger and energy expenditure. Tirzepatide supports leptin’s efficacy by improving insulin sensitivity and reducing inflammation. This makes leptin more effective at signaling for satiety.
Reduces Hunger Hormone
Ghrelin: This is the primary hunger hormone. It is produced by the stomach, with smaller amounts secreted by the pancreas and small intestine. It is crucial in stimulating appetite and regulating metabolism and energy balance. Ghrelin primarily signals to the brain (the hypothalamus specifically). It encourages reward-driven eating by interacting with the dopaminergic system in the brain, contributing to cravings and sometimes overeating. One of the main effects of taking Mounjaro is that it reduces ghrelin, making you feel less hungry between meals and turning the volume down on cravings.
Slows Gastric Emptying
As you begin to digest food, the stomach goes through phases of gastric emptying that help move contents from the stomach to the duodenum (the first part of the small intestine). Typically, this process takes one to two hours.
Taking Mounjaro slows the transit time of food leaving the stomach, making you feel fuller longer.
GIP Enhances Energy Expenditure
Research suggests that GIP may significantly increase energy expenditure and fat utilization (retrieval and oxidation).
Its effects are complex and context-dependent. More research is being done on this, but evidence suggests that the combination of GLP-1 and GIP work synergistically, leading to more weight loss than GLP-1 alone (i.e., Ozempic).
Is Tirzepatide Safe?
What Are The Side Effects of Taking Mounjaro?
Our patients tend to tolerate tirzepatide well, primarily because we coach them with a “low and slow” dosing strategy. That said, below are the most common side effects, which are typically mild and improve over time:
Nausea (most common) - often experienced when starting or increasing the dose
Diarrhea or constipation - GI changes are common, but generally temporary
Stomach cramping or bloating - can be mild to moderate
Vomiting - less common, usually a dosing problem
Excessive loss of appetite - typically can be resolved with lower dose
Acid reflux - food choices and timing can help mitigate
Fatigue - some experience 1-2 days of fatigue following the injection day.
What Are The Risks of Taking Mounjaro?
Gastroparesis (Severe Delayed Stomach Emptying): Some users experience prolonged nausea, bloating, and vomiting due to slowed digestion.
Pancreatitis: Rare but serious inflammation of the pancreas (severe abdominal pain, nausea, vomiting).
Gallbladder issues: Increased risk of gallstones and cholecystitis (gallbladder inflammation).
Hypoglycemia (Low Blood Sugar): More common if used with insulin or sulfonylureas.
Kidney problems: Can worsen dehydration-related kidney issues.
Thyroid tumor risk(in rodents): There’s a warning about possible thyroid C-cell tumors, but human risk is unclear.
Are There Higher Risks or Greater Side Effects With Tirzepatide (vs. Semaglutide)?
At higher doses, studies suggest a bit more nausea and diarrhea when taking tirzepatide
A slightly greater potential for hypoglycemia
Does Mounjaro Cause Muscle Loss?
Tirzepatide can lead to muscle loss, but most weight loss seen in clinical trials is fat mass.
Any significant weight loss - whether through calorie restriction, bariatric surgery, or medication - can lead to muscle mass loss. It is imperative when on a weight loss program to mitigate this effect. See below.
Rapid weight loss, calorie restriction, and nutrition choices can exacerbate muscle mass loss.
Muscle mass loss can be a difficult thing to avoid when cutting calories. With longevity in mind, you are better off being a little overweight with a healthy level of muscle mass than being “thin” with poor muscle mass.
Losing muscle mass sabotages metabolism and longevity.
Reduced physical activity may cause muscle mass loss, as fatigue can be a side effect of this medication.
How To Minimize Muscle Mass Loss When On Mounjaro
In our clinic, we pair every Mounjaro prescription with the following instructions:
Increase Protein Intake: Aim for 1g of protein per pound of body weight daily to preserve muscle.
Strength Training: Resistance training 2 - 4 times weekly helps maintain lean mass.
Stay Active: Incorporate walking, cardio, and bodyweight exercises to support overall muscle retention.
Monitor Weight Loss Pace: Losing weight too fast (>1–2 lbs per week) can increase muscle loss risk.
Stay Hydrated & Get Enough Electrolytes: These help prevent fatigue and support muscle function.
What Happens When You Stop Taking Mounjaro?
What Studies Show About Weight Regain After Mounjaro
According to a phase 3 randomized, double-blind, placebo-controlled trial, nearly 90% of the tirzepatide group maintained the majority (80% or more) of their weight loss over 88 weeks. Still, only 16.6% of those who received the placebo could keep it off. Once patients discontinued tirzepatide, they regained 14% of their lost weight.
Why Does Weight Come Back After Stopping Mounjaro?
Appetite Returns: tirzepatide suppresses hunger, but after stopping, ghrelin (hunger hormone) increases, making it harder to maintain a calorie deficit.
Slowed Metabolism: Rapid weight loss can reduce metabolic rate, leading to faster weight regain once normal eating resumes.
Loss of Lean Mass: If muscle mass is lost during weight loss, metabolism drops, making it easier to gain fat back.
Lifestyle Factors: If users rely solely on the medication without changing diet and exercise habits, weight regain is more likely.
How To Maintain Weight Loss After Stopping Mounjaro
Our clinic pairs every Mounjaro (tirzepatide) prescription with the following prescriptive:
The imperative of maintaining muscle mass
Dedicating to regular strength training and exercise
Focusing on a high-protein diet
Mindful eating and portion control
Gradual weaning off the medication
Are There Additional Health Benefits to Taking Mounjaro To Factor Into The Risk-Benefit Analysis?
While Mounjaro does carry risks, there may be some health benefits of taking this medication that you might consider weighing in your decision-making process.
While Mounjaro studies are still underway, they seem promising. It is reasonable to extrapolate some cardiovascular benefits due to the GLP-1 component:
Lowers CRP: Studies show that Mounjaro can reduce CRP, a marker of inflammation and cardiovascular risk.
Lowers inflammatory cytokines: Mounjaro may reduce inflammatory cytokines like TNF-α, IL-6, and IL-1β.
Reduces Inflammation: Research in mice suggests that Mounjaro may reduce inflammation by targeting the brain.
Reduces heart disease risk
Improves metabolic health: reduces progression of type 2 diabetes
Brain and cognitive benefits: studies show some neuroprotective benefits of this medication
May improve mood and reduce depression
Reduces fatty liver disease
Reduces addictive behaviors: many patients drink less alcohol when taking Mounjaro
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