GLP-1s Outperform Metformin in Prediabetes Risk, MACE

Adults with prediabetes and obesity who took a glucagon-like peptide-1 (GLP-1) medication were about 1.5 times more likely than those on metformin to regulate their blood sugar, while 31% had a lower risk of progressing from prediabetes to type 2 diabetes (T2D), according to an analysis presented at the American Heart Association (AHA) Scientific Sessions 2026.¹

With additional findings of GLP-1s outperforming metformin in reducing major adverse cardiovascular events (MACE), including heart attacks, strokes, and heart failure events, these comparative findings could transform the future standards of care among pharmacists managing diabetes and other related cardiometabolic conditions.

“The great news with prediabetes is that it’s still possible to reverse the progression of the disease,” said Vinicius de Sousa Barzon Serra, MD, study author and research fellow in the department of cardiovascular medicine at the Mayo Clinic, according to the analysis.¹ “This research may add to the case for considering GLP-1 medications earlier for certain patients, rather than waiting until they develop T2D.”

The observational study evaluated electronic health records from 256,492 adults with prediabetes and obesity, comparing patients who received GLP-1 receptor agonists against those prescribed metformin. Beyond glycemic control, GLP-1 therapy was associated with a 41% lower risk of all-cause mortality over a 5-year follow-up period. Patients on GLP-1s experienced 15% fewer heart attacks, 20% fewer strokes, 25% fewer heart failure events, and an 8% reduction in atrial fibrillation cases.

READ MORE: Updated Diabetes Consensus Shifts Focus from Glucose Control to Whole-Person Care

Broader Cardiovascular Protection and Mortality Reduction

These cardioprotective findings arrive at a critical moment for public health, as more than half of all adults in the US are currently impacted by diabetes or prediabetes. Furthermore, 40% of American adults live with obesity, while over 80% of young and middle-aged adults display early signs of cardiovascular-kidney-metabolic risk.²

Despite established clinical goals, only 23% of adults diagnosed with diabetes currently achieve recommended targets for blood pressure, cholesterol, and blood sugar combined.

Robert Eckel, MD, former AHA president, noted that weight loss driven by GLP-1 therapy plays a pivotal role in preventing disease progression and cardiovascular events. He emphasized that although metformin remains a safe, inexpensive, and trusted first-line option, GLP-1 agents represent an impactful secondary or add-on treatment.¹

Surging Public Demand and Evolving Practice Guidelines

Public adoption of GLP-1 medications has accelerated rapidly across the nation. Recent Gallup survey data show that 11% of American adults currently use GLP-1 medications for weight loss, up from just 3% 2 years prior.³

Public awareness of these therapies has reached 91%, with 15% of adults reporting usage at some point. This widespread adoption has coincided with a decline in national adult obesity rates from 39.9% down to 36.4%, while overall diabetes prevalence has stabilized.

Among current users, 68% take brand-name formulations, 19% use compounded alternatives, and 12% remain uncertain about their specific product type.³

In response to expanding clinical evidence, major professional organizations have updated their clinical standards. The 2026 American Diabetes Association Standards of Care Guideline introduced several key updates regarding incretin therapies. Specifically, new recommendations support dual GIP and GLP-1 receptor agonist therapy to reduce heart failure symptoms and cardiovascular events.⁴

The updated guidelines also advise clinicians on individualized dose titration to balance efficacy, tolerability, and clinical benefits, while providing guidance on initiating GLP-1 therapy in specialized populations such as patients on dialysis to lower cardiovascular risk.

Critical Roles and Counseling Responsibilities for Pharmacists

As front-line health care providers, community pharmacists occupy a central position in navigating this shift toward earlier GLP-1 intervention. Pharmacists are frequently called upon to educate patients on subcutaneous injection techniques, proper refrigerated storage, and gradual dose titration schedules.⁵

A cross-sectional survey of 500 community pharmacists revealed a moderate overall knowledge score of 15.8 out of 25 regarding GLP-1 therapies, with significant variability based on practice setting and professional experience. Pharmacists working in high-volume settings exhibited higher knowledge scores, yet notable gaps remained regarding regulatory approval status and dosing protocols.

The survey highlighted key areas where pharmacist counseling can be strengthened. Despite 74.2% of pharmacists regularly informing patients about product storage conditions, only 51% consistently demonstrate proper injection pen use, and 45.6% routinely discuss potential adverse effects like nausea.⁵

Furthermore, over 60% of pharmacists expressed concern over medication misuse and off-label demand driven by cosmetic weight-loss interest. Researchers emphasized that implementing standardized counseling checklists and structured educational programs can empower pharmacists to deliver consistent patient guidance.

By reinforcing proper administration, managing side effects, and advocating evidence-based treatment, community pharmacists can ensure that expanding GLP-1 access translates into safe and effective long-term cardiometabolic care.⁵

“The main effect these findings could have is on the shared decision-making discussion between doctors and patients exploring various treatment options, and the pros and cons for each,” concluded Serra, according to the current release.¹ “Metformin is still a first-line treatment choice. This is less about replacing one medication with another and more about discussing additional options with specific patients.”

READ MORE: Diabetes Resource Center

REFERENCES

1. GLP-1 meds linked to lower diabetes, heart risks than standard diabetes prevention med. American Heart Association. News Release. November 2, 2026. Accessed November 3, 2026. https://newsroom.heart.org/news/glp-1-meds-linked-to-lower-diabetes-heart-risks-than-standard-diabetes-prevention-med

2. Palaniappan LP, Allen NB, Almarzooq ZI, et al. 2026 heart disease and stroke statistics: a report of US and global data from the American Heart Association. Circulation. January 21, 2026. DOI: 10.1161/CIR.0000000000001412

3. Gunn J. Here's how many Americans say they are now taking GLP-1 drugs. Fox 6 Milwaukee. July 10, 2026. Accessed November 3, 2026. https://www.fox6now.com/news/heres-how-many-americans-say-now-taking-glp-1-drugs

4. 2026 ADA Standards of Care in diabetes guideline now available — key recommendation updates. Guideline Central. December 12, 2025. Accessed November 3, 2026. https://www.guidelinecentral.com/insights/dec-2025-ada-diabetesstandardsofcare-guideline-spotlight/

5. Bayram-Ozgur D, Demirtürk E, Sar Y. Community pharmacists' knowledge and counseling competence on GLP-1 receptor agonists in obesity and type 2 diabetes care in Türkiye: a cross-sectional study. Diabetes Metab Syndr Obes. 2026;19:587750. 2026 Mar 3. doi:10.2147/DMSO.S587750