Glucagon-like peptide-1 (GLP-1) receptor agonists are a newer class of diabetes drugs that have the potential to double as weight loss drugs, widening their lucrative market potentials.
While weight loss effects can vary depending on the drug, studies show that all GLP-1 meds can result in an average weight loss of about 10.5 to 15.8 pounds.
Leading in the GLP-1 agonist diabetes arena are Eli Lilly’s recently approved Mounjaro (tirzepatide) and Novo Nordisk’s Ozempic (semaglutide), which has been a top seller for Novo since it first launched in 2017.
Mounjaro is a dual-targeting drug as it also targets the glucose-dependent insulinotropic polypeptide (GIP) receptor, making it the first-in-class GIP/GLP-1 receptor agonist for the treatment of type 2 diabetes.
Novo’s obesity version of semaglutide (at a higher dose) is marketed as Wegovy and was approved in 2021. Lilly is also working towards an obesity treatment form of tirzepatide, with trials currently underway to evaluate its weight loss effects.
The obesity drug market is currently valued at $2.82 billion and could reach $54 billion by 2030 with the advent of drugs like GLP-1 agonists that have clinically proven weight loss effects.
Additionally, GLP-1 analogs like Mounjaro and Ozempic have also been shown to have other metabolic benefits, including lowering the risk of heart disease, stroke and kidney disease.
Since Mounjaro’s May US Food and Drug Administration (FDA) approval, sales of the drug have skyrocketed beyond initial expectations owing to patient demand and a temporary shortage of Novo’s Ozempic.
And the demand won’t be easing anytime soon. The incidence of diabetes is on the rise with 11.3 percent of the US population (37.3 million or roughly one in ten Americans) currently having the condition. Of this number of diabetics, roughly 90 to 95 percent have type 2 diabetes. According to some estimates, if trends continue, one in five could have diabetes by 2025. The prevalence of diabetes could increase to more than 54.9 million between 2015 to 2030, and deaths attributed to it will increase by 38 percent to more than 385,000 people per year.
Accordingly, the diabetes drug market is expected to balloon from $29.81 billion in 2021 to $61.6 billion by 2030.
What Are GLP-1 Agonists?
GLP-1 receptor agonists, or incretin (metabolic hormones) mimetics, are analogs of the GLP-1 peptide hormone that binds to the GLP-1 receptor to regulate blood sugar levels by boosting insulin secretion.
The first GLP-1 receptor agonist approved by the FDA was exenatide, which received approval in April 2005 for the treatment of type 2 diabetes. Since then, several more GLP-1 agonists have been approved by the FDA.
Why GLP-1 Agonists?
Analogs of GLP-1 have emerged as attractive diabetes treatments because of their favorable safety and efficacy profiles in lowering blood glucose levels through pancreatic beta‐cell‐mediated glucose‐dependent insulin secretion and suppression of glucagon release. They can also slow gastric emptying and promote satiety.
In addition to their significant effectiveness in glycemic control and weight/fat mass reduction, they’ve also been shown to decrease the risk of heart disease, heart failure, stroke and kidney disease. Eli Lilly is currently evaluating Mounjaro in clinical trials for heart failure (HF) patients, potentially expanding its use in type 2 diabetic, overweight and obese patients to patients with heart conditions.
Mounjaro Versus Ozempic
Below are details about how GLP-1 competitors Mounjaro and Ozempic match up against each other.
The active ingredient in Mounjaro is tirzepatide which is a dual GIP and GLP-1 receptor agonist while Ozempic contains semaglutide as its active ingredient, which is a single GLP-1 receptor agonist.
Mounjaro and Ozempic are both FDA approved for glycemic control in adults with type 2 diabetes, in combination with diet and exercise.
Mounjaro and Ozempic are both administered as subcutaneous injections once a week. They can be injected under the skin of the upper arm, stomach or thigh. Their once-a-week administration makes them more convenient and easier to use compared to taking a daily pill or shot of insulin.
Mounjaro is given at an initial dose of 2.5 mg and after four weeks, increased to 5 mg.
Ozempic can be prescribed in three different doses: 0.25, 0.5 or 1 mg with a maximum recommended dose of 2 mg.
Novo also offers semaglutide in an oral pill form (marketed as Rybelsus), making it the first oral biologic medication for type 2 diabetes taken as a daily capsule. It is given at a higher dose than the injectable version, at 3 mg once a day for 30 days. Afterward, the dose can then be adjusted by a patient’s doctor but it typically would not exceed 14 mg once a day.
Mechanism of Action
Ozempic is a GLP-1 receptor agonist that binds to the GLP-1 receptor to activate it, mimicking the action of the body’s endogenous GLP-1 hormone on the receptor. Activation of the receptor leads to insulin secretion to lower blood glucose levels.
In contrast, Mounjaro is both a GLP-1 receptor and GIP receptor agonist. The dual action of Mounjaro gives it an advantage over Ozempic as it simultaneously targets two hormone receptors involved in insulin regulation, leading to better A1C and weight reductions.
How Do They Measure Up?
Both Mounjaro and Ozempic effectively lower blood sugar levels, A1C levels and promote reductions in body weight. In Eli Lilly’s head-to-head trials, Mounjaro demonstrated superiority to Ozempic in measures of fat mass reduction and time to achieving A1C and weight reduction targets.
Mounjaro has therefore emerged as the clear winner in glycemic control and weight loss.
This is because Mounjaro is not just a GLP-1 agonist because also contains a GIP agonist, having dual action in mimicking two key hormones involved in the regulation of insulin release and appetite. GIP is a metabolic hormone that promotes insulin secretion and also weakly inhibits gastric acid secretion to suppress appetite.
Ozempic also has favorable impacts on cardiovascular outcomes, reducing stroke risk by 39 percent and myocardial infarction risk by 26 percent in trials.
Common side effects of Mounjaro include nausea, vomiting, diarrhea, decreased appetite, constipation, indigestion and abdominal pain.
Common Ozempic side effects include feeling sick, vomiting, diarrhea, abdominal pain and constipation.
More serious side effects of Mounjaro include: potential of thyroid tumors including thyroid cancer; pancreatitis; hypoglycemia; serious allergic reactions; serious kidney, stomach and gallbladder problems; and vision changes.
The serious side effects of Ozempic may include thyroid tumors; kidney problems including kidney failure; pancreatitis; severe allergic reactions; vision changes; and hypoglycemia.
Overall, it appears the side effects of Mounjaro versus Ozempic are largely comparable.
The list price of Mounjaro is $974.33 per fill while Ozempic’s ranges from $1,205 to $1,368, making the cost of the two comparable. The final cost to patients depends on the type of insurance plan they have.
They are significantly higher in price than older, conventional diabetes treatments such as biguanides like metformin as Mounjaro and Ozempic are still on patent and are biologics, which tend to be more expensive given their complexity.
Ozempic and Rybelsus (oral semaglutide) have proven to be blockbusters for Novo Nordisk, with Ozempic being the company’s top selling drug in 2021 with global sales reaching over 33 billion kroner or just over $4.5 billion. Sales of Ozempic were up by 28 percent in Q3 of 2022, driven by high demand for GLP-1-based diabetes treatments. Its third quarter operating profit increased by more than 30 percent to total $2.4 billion (20.2 billion Danish crowns).
Novo now has its eyes set on its weekly semaglutide injection Wegovy for weight loss and obesity, which has been shown in trials to reduce body weight by about 12 percent. It received FDA approval in June 2021 as an obesity medication and has already received informal endorsements from celebrities like Kim Kardashian, Elon Musk and TikTok influencers.
For Eli Lilly, Mounjaro has taken off to the races extremely strong since its spring approval this year, surpassing market expectations by more than double. In its first quarter on the market in the US, total sales between July and September amounted to $97 million.