For many patients—especially those with pre-diabetes or diabetes—losing weight requires more than just diet and exercise. Achieving this often-elusive goal requires addressing the hormonal underpinnings of metabolism.

Fortunately, new drugs are making weight loss easier. And another pharmaceutical agent that appears to be on the cusp of FDA approval may prove to be a game-changer.

 

Evaluating tirzepatide for obesity

Tirzepatide (Mounjaro) is a subcutaneous long-acting injection currently indicated for type 2 diabetes management.

Tirzepatide (subcutaneous route): description and brand names. Mayo Clinic. Updated August 1, 2022.

Used in conjunction with diet and exercise, this glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist has been shown to help patients who do not have atherosclerotic cardiovascular disease control blood glucose levels, particularly when weight loss is an important consideration.

 

Since this medication is known to reduce food intake, physicians have been prescribing tirzepatide off-label for weight loss for years because it suppresses appetite. But unlike other drugs in its class, tirzepatide targets GLP-1 and GIP receptors.

FDA approves new drug treatment for chronic weight management, first since 2014. US Food & Drug Administration. June 4, 2021.

These incretins (hormones that are released from the gut into the bloodstream in response to ingestion of food) increase communication between the pancreas and stomach, making insulin secretion more efficient while decreasing gastric emptying and increasing satiety.

 

A July 2022 phase 3 double-blind, randomized, controlled trial published in the New England Journal of Medicine found that 5, 10, or 15 mg doses of tirzepatide, administered weekly, led to “substantial and sustained” weight loss.

Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387(3):205–216.

 

The trial involved about 2,500 adults with a BMI of 30 or more and spanned 72 weeks. Researchers evaluated for coprimary endpoints of percentage change in weight from baseline and weight reduction of at least 5%. After 72 weeks, participants showed a mean percentage weight change of -15%, -19.5%, and -20.9% among each of the respective dosage groups. Among the same groups, 85%, 89%, and 91% saw a total weight loss of at least 5%.

 

More options for obesity and weight loss

These data points are harmonious to the ears of Ana Maria Kausel, MD, a New York-based endocrinologist and entrepreneurial physician who is launching an endocrinology telemedicine startup. She said FDA approval of tirzepatide may help patients who have stalled on their weight-loss journeys.

Some people tell you that they eat 800 or 1,000 calories per day, and they don’t lose a single pound—and it’s frustrating.

“I think doctors should have a lower threshold to prescribe these medications,” Dr. Kausel added, citing a few others that have proven to be beneficial. “They are super-safe and have minimal side effects. You just have to educate the patient.”

In addition to tirzepatide, such medications include:

Prescription weight-loss drugs. Mayo Clinic. Updated November 4, 2020.

 

• Phentermine-topiramate: An appetite suppressant that combines the weight-loss drug with an anticonvulsant. It’s approved for short-term weight loss (less than 12 weeks), but this medication does come with dangerous potential side effects such as misuse, abuse, and an increase in birth defects.

• Bupropion-naltrexone: Combining an alcohol/opioid dependence drug with an antidepressant, bupropion-naltrexone also suppresses appetite. Dr. Kausel cautioned that patients on this drug often rebound and regain their weight.

• Liraglutide: A (GLP-1) receptor agonist type 2 diabetes drug that promotes weight loss in higher doses.

• Semaglutide: Indicated for adults with obesity or those who are overweight and also have at least one weight-related condition such as hypertension, type 2 diabetes, or hyperlipidemia. It’s used with diet and exercise.

• Orlistat: Also available over the counter in a lower dose, orlistat decreases dietary fat absorption in the intestines, but it can have some unpleasant side effects including loose stools and flatulence.

 

Off-label options

Tirzepatide isn’t the only off-label option at the disposal of endocrinologists. Several diabetes drugs support weight loss by targeting GLP-1, including semaglutide and dulaglutide.

While these are good options, Dr. Kausel felt tirzepatide is better, because it targets both the GLP-1 and GIP pathways, as opposed to just one pathway, leading to better weight loss.

Metformin is also a strong supportive option, she added, saying, “These medications in combination with metformin have the best efficacy. It’s a very old-fashioned and cheap medication that, in combination with all of these things, works because metformin opens the door for insulin to enter the cell.”

 

Controlling cost

The maker of tirzepatide, Lilly, is currently offering coupons for the medication, but it’s not clear how long those will be available for a drug that must be taken long-term.

To control patient costs, Dr. Kausel said that many of these drugs are available at lower prices overseas. And, if you have a prior authorization team, lean on it.

“If you have a staff just dedicated to prior authorizations, it makes everyone happy,” she said. “It makes the patient happy. It makes the physician happy. A patient starts taking the weight-loss meds, they start losing weight, they want to come and see you. It has such a big impact on quality of life."

When you help someone lose weight, I think it’s completely worth it.