Semaglutide and tirzepatide are both recommended in the American Diabetes Association's 2023 Standards of Care in Diabetes as highly effective options for lowering blood glucose and weight management. So, which should be initiated first, and under what conditions?
Another Great Debate — Semaglutide versus Tirzepatide for Type 2 Diabetes and Obesity, presented Dec. 4 at the Midyear Clinical Meeting & Exhibition, walked pharmacists through this advanced exercise in shared decision-making and encouraged them to “think smart” about the many treatment options available today.
The patient in the real-world case scenario was a 45-year-old non-Hispanic white woman with a personal history of hypertension and prediabetes, treated with lisinopril and metformin, respectively. Family history, a smoking habit, and a body mass index of 34.7 kg/m2 put her at higher risk for cardiovascular (CV) disease. The patient’s most recent laboratory tests — with a fasting blood glucose of 189 mg/dL and a glycated hemoglobin (A1c) level of 8.2% — indicated she had progressed to type 2 diabetes within the last six months. She had struggled to lower her blood glucose levels and lose weight through lifestyle modifications.
Based on the initial information, the audience was asked which medication they would recommend for this sample patient. A slight majority voted for tirzepatide over semaglutide.
Then, claiming an “even playing field,” the presenters launched into a spirited debate of the pros and cons of these highly effective, subcutaneous injectables.
First up was Jennifer N. Clements, clinical professor and director of pharmacy education at the University of South Carolina College of Pharmacy, who made the case for semaglutide as a tried-and-true treatment for both type 2 diabetes and obesity. She claimed the glucagon-like peptide 1 (GLP-1) receptor agonist was “the way to go” for its mechanism of action, affecting both insulin secretion and appetite suppression, and its “superior” effect on CV outcomes.
Clements summarized the strong evidence base for semaglutide from the SUSTAIN-6, SUSTAIN FORTE, and STEP 2 clinical trials. Semaglutide has been shown to reduce A1c by 2.2 percentage points and lower body weight by nearly 10%. She recommended the 2.4-mg semaglutide formulation to help the case study patient reach and maintain her blood glucose and weight targets with low risk for hypoglycemia, and to protect against future heart disease.
With semaglutide, she said, “you get more bang for your buck.” The medication’s adverse effects, such as gastrointestinal reactions and injection-site reactions, can be managed with effective counseling.
At age 45, the patient is younger than most of the participants in the studies of semaglutide. But with her being at such high risk for CV issues, Clements argued, why would you wait to initiate treatment?
Diana Isaacs, clinical pharmacy specialist at the Cleveland Clinic Diabetes Center, took the stage to make the case for tirzepatide. She praised the medication as a dual incretin (activating the GLP-1 and gastric inhibitory polypeptide receptors). Then there’s tirzepatide’s better device design: The single-use pen is simpler to use, she said, and patients “never have to see the needle,” which can help overcome any resistance to injections.
Isaacs went on to demonstrate how tirzepatide has proven more effective at lowering A1c and body weight compared with other treatments, including semaglutide. In the series of SURPASS clinical studies, tirzepatide was “superior at every dose” from 5 mg to 15 mg, lowering A1c by 0.6 percentage points more than semaglutide 1 mg. When it came to weight loss in SURPASS-2, the difference was even more dramatic: -11.4% for tirzepatide vs. -6.7% for semaglutide.
Tirzepatide tends to be well tolerated, Isaacs said. Nausea is common, but the side effect tends to be transient and manageable. The medication’s impact on CV outcomes is still being studied, Isaacs admitted — but in her opinion, that was not highly relevant for the patient at hand, who did not yet have established heart disease.
After Clements and Issacs each gave a good-humored rebuttal, the contest was put to another audience vote. Which treatment would they initiate for this hypothetical patient: semaglutide 0.25 mg subcutaneously once a week or tirzepatide 2.5 mg subcutaneously once a week?
This time, it was a close call. Clements and Isaacs agreed to a tie: Both semaglutide and tirzepatide are outstanding options for treating type 2 diabetes and obesity.
The presenters concluded that we are living in an “incredible time” with more treatment options than ever for these comorbid conditions. The right therapies, combined with lifestyle changes like diet and exercise, can greatly improve a patient’s long-term health outcomes and quality of life.
Ultimately, the patient with type 2 and obesity will choose their preferred treatment based on their individual needs and preferences, as well as health insurance coverage and budget. Clements and Isaacs acknowledged the high cost of semaglutide and tirzepatide, especially for patients without insurance, and encouraged pharmacists to steer their patients toward cost-saving measures, such as assistance programs and 340B Drug Pricing Program clinics.
That, Clements and Isaacs said, is the essence of person-centered healthcare. Over time, Isaacs hoped, “we can finally make a dent in type 2 diabetes and obesity.”