Eli LIlly’s tirzepatide (Monjaro) could become the most popular weight-loss drug ever if approved, but there are significant concerns about if it will be affordable and accessible to those who need it.
Tirzepatide, currently used to regulate blood sugar in adults with type 2 diabetes (T2D), is expected to be approved by the U.S. Food and Drug Administration (FDA) for weight loss in 2023. Tirzepatide was FDA approved in May 2022 as a once-weekly injection to help improve blood sugar as an addition to diet and exercise, but researchers noted that those taking it also experienced significant weight loss.
Why is tirzepatide different from other GLP-1s?
The class of glucagon-like peptide-1 (GLP-1) receptor agonists have been on the market since AstraZeneca’s exantide (sold under the brand name Byetta) was approved by the FDA in 2005. In the last 18 years they have become a standard of care in patients with T2D, alongside newer sodium–glucose cotransporter 2 (SGLT2) inhibitors, and the tried-and-true therapies of metformin and injectable insulin.
Like many of the GLP-1 receptor agonists on the market, tirzepatide is a once-weekly injection used in combination with lifestyle modification to control blood sugar and support weight loss. But tirzepatide isn’t just a GLP-1; it’s a dual-action agent, pairing GLP-1 AND glucose-dependent insulinotropic polypeptide (GIP)receptor agonists to reduce appetite, improve the body’s breakdown of sugar and fat, and regulate blood sugar.
Both GLP-1 and GIP are intestinal hormones with a broad range of physiological actions that include stimulating insulin secretion to lower blood sugar and stimulating glucagon secretion to raise it. But, in addition, GIP is known to play a role in lipid metabolism and fat deposition, which may explain why tirzepatide is so effective for weight loss. The elements of the drug “work together to improve how the brain sees weight, which leads to weight loss and better blood sugar regulation” says obesity medicine physician-scientist Dr. Fatima Cody Stanford.
“Tirzepatide is a dual incretin agonist drug. The incretins are hormones released by the gut to help manage blood glucose levels after a meal. Incretins trigger the pancreas to release glucose-lowering insulin while blocking glucagon, which would raise glucose levels by mobilizing it from liver stores,” – Dr. Robert Gabbay, chief scientific and medical officer for the American Diabetes Association
Evidence for weight loss
In clinical trials, patients lost an average of 22.5% of their body weight on tirzepatide compared to diet and placebo. In phase 3 clinical trials, patients lost an average of 15 more pounds with tirzepatide than with a placebo and an average of 23 pounds more than the placebo group when they used tirzepatide and insulin. Its use is expected to expand to include weight loss treatment thanks to impressive findings in a phase 3 clinical trial. In the trial, researchers found that patients lost an average of 22.5% of their body weight (or about 52 pounds). By comparison, similar weight loss drugs Wegovy and Saxenda reduced body weight by around 15% (Wegovy) and 5% (Saxenda).
“We are pleased with the FDA’s decision to grant Fast Track designation for tirzepatide, and we look forward to completing our rolling submission next year. Obesity is a chronic disease that impacts the health of nearly 100 million Americans and is a significant driver of healthcare costs. While diet and exercise are important steps, most patients don’t achieve their desired treatment goals with only diet and exercise. We are dedicated to helping people living with obesity through our research and development of innovative treatments like tirzepatide, which produced significant weight reductions in patients taking tirzepatide for type 2 diabetes in SURPASS. Tirzepatide also helped nearly two-thirds of participants on the highest dose reduce their body weight by at least 20 percent in SURMOUNT-1.” – Mike Mason, president, Lilly Diabetes.
Other therapeutic targets
Not only is tirzepatide is in Phase 3 development for adults with obesity, or overweight with weight-related comorbidity, it is also being studied as a potential treatment for heart failure with preserved ejection fraction (HFpEF), obstructive sleep apnea (OSA), and non-alcoholic steatohepatitis (NASH). Studies of tirzepatide in chronic kidney disease and in reducing the morbidity and mortality in obesity are also planned. The majority of patients with type 2 diabetes, HFpEF, OSA, and NASH, if overweight, would benefit from weight loss. The power of this drug, say experts, really lies in early use, perhaps right after diagnosis, to lower weight and prevent these conditions from progressing to late- or end-stage.
Dr. Anne Peters’ expert perspective
Cardiometabolic Health Congress (CMHC) faculty member and respected diabetes expert Anne L. Peters, MD, weighed in on tirzepatide’s promise for weight loss, as demonstrated in the SURPASS trial. Her primary concern is the safety of her patients, so she says personally she’d like more safety information, particularly with regards to gastrointestinal side effects. Aside from that, Dr. Peters said the SURPASS clinical trial, with its impressive 13,000 participants with type 2 diabetes around the globe, strongly demonstrated tirzepatide not only reduced A1C from baseline but had exciting possibilities for secondary endpoints like weight, cardiovascular and kidney markers.
“If you look at the data that we’ve seen thus far they’re pretty darn impressive in terms of A1C reduction and weight loss and hopefully there’ll be another tool that we have to treat our patients with type 2 diabetes.” – Dr. Peters
- Lilly receives U.S. FDA Fast Track designation for tirzepatide for the treatment of adults with obesity, or overweight with weight-related comorbidities
- Tirzepatide Once Weekly for the Treatment of Obesity
- FDA Approves Novel, Dual-Targeted Treatment for Type 2 Diabetes