You’ll hear debate about the role of injectable tirzepatide (Zepbound) or semaglutide (Wegovy) for obesity.
Tirzepatide is the same ingredient in Mounjaro for type 2 diabetes. It’s a dual agonist...at glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors.
Semaglutide is the same GLP-1 agonist in injectable Ozempic or oral Rybelsus for type 2 diabetes.
These meds increase satiety and slow gastric emptying...which may lead to weight loss in people with or without diabetes.
For example, tirzepatide 15 mg weekly PLUS lifestyle changes lead to about 41 pounds more weight loss than placebo over about a year in patients without diabetes.
And semaglutide 2.4 mg weekly leads to about 27 pounds more weight loss than placebo in patients without diabetes.
Think of tirzepatide or semaglutide as more effective than other weight loss meds. For instance, liraglutide leads to roughly 11 pounds of weight loss...or phentermine/topiramate to about 19 pounds.
Also, new data suggest that adding semaglutide 2.4 mg weekly for patients with overweight or obesity and CV disease prevents 1 CV event for every 67 patients treated over about 3 years.
Results from a similar study with tirzepatide aren’t due until 2027.
But it’s not all smooth sailing with these meds.
Tirzepatide or semaglutide commonly cause GI upset, especially during dose escalation. And both carry warnings for rare pancreatitis or gallbladder disease...and are linked to bowel obstruction.
Either med costs about $1,200/month...many payers don’t cover these or require a prior auth...and high demand can cause shortages.
Plus patients may need to use these meds long-term...since weight gain is common when stopping.
Continue to emphasize lifestyle changes first for weight loss.
Save weight loss meds as an option for patients with a BMI of 30 or more...or 27 or more plus a weight-related condition (diabetes, etc).
If trying a med for weight loss, tailor the selection based on weight loss goals, comorbidities, cost and access, etc.
If practical, consider tirzepatide for patients with severe obesity, since it may lead to more weight loss...or suggest semaglutide for patients with CV disease based on CV benefit.
Ensure these meds are titrated slowly to minimize GI effects.
For example, start tirzepatide at 2.5 mg weekly and increase by 2.5 mg every 4 weeks as tolerated...up to a max of 15 mg/week.
Counsel to expect modest GI upset...but to promptly report severe pain. It can be a red flag for gallbladder issues or pancreatitis.
See our related article for the role of oral weight loss meds.
Refer to our resource, Weight Loss Products, for other considerations...drug interactions, monitoring, and more.
- Grunvald E, Shah R, Hernaez R, et al; AGA Clinical Guidelines Committee. AGA Clinical Practice Guideline on Pharmacological Interventions for Adults With Obesity. Gastroenterology. 2022 Nov;163(5):1198-1225.
- American Diabetes Association Professional Practice Committee. 8. Obesity and Weight Management for the Prevention and Treatment of Type 2 Diabetes: Standards of Care in Diabetes-2024. Diabetes Care. 2024 Jan 1;47(Suppl 1):S145-S157.
- Jastreboff AM, Aronne LJ, Ahmad NN, et al; SURMOUNT-1 Investigators. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022 Jul 21;387(3):205-216.
- Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Mar 18;384(11):989-1002.
- Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med. 2023 Dec 14;389(24):2221-2232.
- Chart: Weight Loss Products