Semaglutide and Tirzepatide Lead the Way in Comprehensive Diabetes and Obesity Management

As new evidence expands the therapeutic scope of glucagon-like peptide-1 (GLP-1) receptor agonists (RAs), pharmacists are uniquely positioned to guide patients through an increasingly complex landscape of diabetes care, weight management, and cardiovascular and renal risk reduction. GLP-1 RAs, including semaglutide (Ozempic, Wegovy, Rybelsus; Novo Nordisk Inc), are revolutionizing the treatment of diabetes, with opportunities to improve glycemic control, stabilize hemoglobin A_1c (HbA_1c) levels, reduce poor cardiovascular outcomes, and induce robust weight loss.^1,2

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Further, the current class of FDA-approved GLP-1 medications is set to be surpassed by new treatments in the pipeline. At a recent Pharmacy Times Clinical Forum in Boston, Massachusetts, clinicians reviewed emerging clinical trial data. They shared real-world insights on integrating GLP-1 therapies into holistic diabetes management, addressing glycemic control, cardiovascular risk, kidney protection, and weight loss outcomes.¹

“I feel like pharmacists live off the data,” said moderator Katelyn O’Brien, PharmD, BCPS, CDCES, BC-ADM, clinical pharmacy specialist and certified diabetes care and education specialist at Boston Medical Center in Massachusetts, during the forum. “We know the numbers. We can compare the trials. It’s so important to have these foundations and evidence-based medications because doctors truly do trust us. And they’ll come to us, and they’ll say, ‘Which one should I pick?’"¹

Through reviewing evidence from clinical trials and real-world patient experiences, the expert panel sought to more thoroughly determine the primary role of GLP-1 RAs in glycemic control and diabetes care. In addition to weight loss, studies are now examining the use of GLP-1s in overall weight management, reducing insulin dependence, and the effectiveness of these agents in diverse subgroups. Furthermore, GLP-1 RAs such as semaglutide are gaining indications beyond diabetes, including for reducing cardiovascular risk and for renal management.¹

Weight Loss and Cardiovascular Risk

Semaglutide, a GLP-1, and tirzepatide (Mounjaro, Zepbound; Eli Lilly and Company), a dual gastric inhibitory polypeptide and GLP-1, have been proved to be efficacious in inducing weight loss for patients with type 2 diabetes (T2D). The SUSTAIN family of clinical trials (eg, NCT02054897 and NCT01720446) evaluated semaglutide in a multitude of settings that ultimately demonstrated significant glycated HbA1c reductions and weight loss in drug-naive patients and compared with standard-of-care options for glycemic control. In a series of comparator trials, semaglutide demonstrated superior weight loss and HbA_1c reductions compared with dulaglutide and liraglutide.¹

Crucially, in the SURPASS2 clinical trial (NCT03987919), investigators found tirzepatide to be superior to semaglutide 1 mg, demonstrating heightened reductions in HbA1c and weight loss. The experts discussed real-world experiences of switching patients to tirzepatide when they are not at their weight loss goal using semaglutide or other agents. Rachel Fernandes, PharmD, BCACP, CDCES, an ambulatory care clinical pharmacy specialist at Beth Israel Deaconess Medical Center in Boston, Massachusetts, emphasized the importance of patient-centered discussions when deciding whether it would benefit an individual to switch to tirzepatide. She also noted the insurance considerations, including involvement with formularies and prior authorization, that come into play when making these decisions.³

“I know I gave a talk to our new residents when they first started…in the sense of, ‘These are the options; insurance is a barrier,’” Fernandes said during the Clinical Forum.¹

Although tirzepatide outperforms semaglutide and other standard care options, including insulin, in weight loss and HbA_1c reduction for T2D and obesity, cardiovascular and renal considerations may lead a pharmacist to suggest one treatment over the other. Data from clinical trials, primarily SUSTAIN-6 (NCT01720446), have demonstrated significant reductions in major adverse cardiovascular events (MACE) compared with placebo for semaglutide, accompanied by a substantial decrease in nonfatal stroke. When compared with results from cardiovascular outcome trials of liraglutide or dulaglutide, semaglutide is superior to both and carries an FDA indication to reduce the risk of MACE in patients with T2D.¹

Although it was found to lower the risk of worsening heart failure in patients with heart failure with preserved ejection fraction and obesity in the SUMMIT trial (NCT04847557), tirzepatide has not been compared directly with semaglutide for this indication or at all for reducing the risk of MACE in patients with T2D. Trials investigating tirzepatide in this indication are ongoing, but until these are complete, pharmacists may prefer to prescribe semaglutide.^1,4

“If we care about cardiovascular risk, I’m sure [tirzepatide] is likely to have a similar benefit, but we don’t know the data yet,” Hailey Choi, PharmD, BCACP, CDCES, associate professor of pharmacy practice at Massachusetts College of Pharmacy and Health Sciences School of Pharmacy in Boston, said during the forum. “I would be leaning more toward [semaglutide] knowing what we have in the data.”¹

Renal Benefits and Insurance Implications

Chronic kidney disease (CKD) is also often observed in patients with T2D and can significantly raise the risk of kidney failure, cardiovascular events, and death. Select GLP-1 RAs have been evaluated in clinical trials to assess their potential to reduce the risk of major kidney disease events and kidney failure. Semaglutide, liraglutide, and dulaglutide have been evaluated in completed cardiovascular outcomes trials that included renal outcomes, though O’Brien notes that these were secondary end points in the studies.¹

In the LEADER (NCT01179048) and REWIND (NCT01394952) trials, liraglutide in patients with T2D and high cardiovascular risk and dulaglutide in a broad T2D population, respectively, improved composite renal outcomes. However, semaglutide is the most extensive renal therapy to date, with a secondary outcome in the SUSTAIN-6 trial and a pivotal primary outcome of CKD progression in patients with T2D in the FLOW trial (NCT03819153).^1,5

Investigators from SUSTAIN-6 found that semaglutide reduced new or worsening nephropathy by 36% in patients with T2D, a critical marker of CKD. Most recently, results from FLOW demonstrated semaglutide’s effectiveness compared with placebo in reducing the risk of major kidney events in patients with CKD and T2D. Given the significant benefits for patients with CKD, the FDA approved a new indication for semaglutide––to reduce the risk of estimated glomerular filtration rate decline, end-stage kidney disease, and cardiovascular death in patients with T2D and CKD.^1,5

With insurance and prior authorization constituting major hurdles to the swift prescribing of GLP-1 for patients, being able to point to FDA-approved indications for cardiovascular and renal management is extremely helpful in gaining coverage for semaglutide and other drugs, explained Emily Canuel, PharmD, a clinical pharmacist at Greater Lawrence Family Health Center in Somerset, Massachusetts.¹

“I think it’s been beneficial in terms of coverage, being able to use the argument that semaglutide injectables now have this renal benefit,” Canuel said during the forum. [It means] being able to get patients, who may have had to go through a stepwise approach or may not previously have qualified, those medications.”¹

Semaglutide’s ability to provide weight loss and kidney improvements could influence patients’ preference for the drug over other agents that gain multiple indications in the future, explained Kaitlin O’Rourke, PharmD, BCPS, an advanced practice clinical pharmacist at Brigham and Women’s Hospital in Boston, Massachusetts.¹

“[With] the high co-pays, we’re [doing patients a] disservice,” O’Rourke said. “We might have to [revisit] the GLP-1 [prescription] because we have been able to see the weight loss, but not the kidney benefit. But now we’re like, ‘Oh, thank goodness.’ You’re getting that if you can’t afford to buy both, so it’s a big deal.”¹

Patient Selection and Management for GLP-1 Therapy

With so many GLP-1 options available, pharmacists are essential in counseling patients on available therapies based on their disease presentation, designating proper titrations and dosing schedules, and monitoring potential adverse effects. Pharmacists should ensure their patients are educated on the myriad positive health benefits associated with GLP-1 use beyond weight loss, including improvements in mental health and cardiovascular markers such as hypertension, according to Canuel.¹

“The other nice thing with GLP-1s is they cause this cascade effect on a holistic level for patients where…they start to experience this weight loss and suddenly they have this energy that they didn’t have before, and then they start exercising and feeling motivated to change their diet. Then they’re shedding all this weight, and…their blood pressure starts to look better,” Canuel said. “It’s not necessarily just the weight loss we’re looking to achieve; it’s this global bettering of the patient.”¹

With a broad population indicated for its use, semaglutide is one of the more reliable and efficacious GLP-1s available on the market today. Patients with T2D or obesity who are considering initiating a GLP-1 such as semaglutide—especially those with high cardiovascular risk or CKD—should have extensive discussions with their pharmacist to evaluate their suitability for treatment.¹

REFERENCES

1. O’Brien K, Fernandes R, Choi H, Canuel E, O’Rourke K. Beyond glycemic control: integrating GLP-1 agonists into comprehensive diabetes management. Presented at: Pharmacy Times Clinical Forum; June 12, 2025; Boston, MA.

2. Banting & Best: the discovery of insulin. UMass Chan Medical School. Accessed June 25, 2025. https://www.umassmed.edu/dcoe/diabetes-education/patient-resources/banting-and-best-discover-insulin/#:~:text=Insulin%20treatment%20begins%20for%20humans&text=On%20January%2011%2C%201922%2C%2014,injection%20as%20treatment%20for%20diabetes

3. Frías JP, Davies MJ, Rosenstock J, et al; SURPASS-2 Investigators. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Engl J Med. 2021;385(6):503-515. doi:10.1056/NEJMoa2107519

4. Packer M, Zile MR, Kramer CM, et al; SUMMIT Trial Study Group. Tirzepatide for heart failure with preserved ejection fraction and obesity. N Engl J Med. 2025;392(5):427-437. doi:10.1056/NEJMoa2410027

5. Perkovic V, Tuttle KR, Rossing P, et al; FLOW Trial Committees and Investigators. Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes. N Engl J Med. 2024;391(2):109-121. doi:10.1056/NEJMoa2403347