The evolution of GLP-1s

The evolution of GLP-1s Developing a holistic, personalized approach to deliver long-term value and improve health outcomes

Contents 1 Our clinical position...................................................... 2 Drug pipeline....................................................................... 5 Spend and trend.............................................................. 6 Management strategies........................................... 8 Looking ahead................................................................. 12 Introduction...........................................................................

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Reduces

Introduction

Insulin released

• Blood sugar • Appetite

GLP-1s Taken orally or subcutaneously

Drugs classified as glucagon-like

How GLP-1s work

The rising cost of weight management

peptide-1 (GLP-1) receptor agonists

GLP-1s may be administered subcutaneously or taken orally. For people with type 2 diabetes, these drugs mimic the action of the glucagon-like peptide-1 hormone. When blood sugar levels start to rise after someone eats, GLP-1s stimulate the body to produce more insulin, inhibiting the release of glucagon (a hormone that stimulates the liver to release sugars).

Demand for GLP-1s has soared in the past two years. Nearly 73% of U.S. adults have overweight or obesity, costing the U.S. health care system approximately $173B a year.1 The Food and Drug Administration (FDA) has approved select injectable GLP-1 therapies specifically for weight loss, including semaglutide (Wegovy), liraglutide (Saxenda), and the GLP-1/glucose-dependent insulinotropic polypeptide (GIP) dual-acting therapy tirzepatide (Zepbound). Similarly, in late 2023, tirzepatide (Zepbound) was approved for obstructive sleep apnea with obesity.

have historically been used to manage type 2 diabetes. This is partly due to their effectiveness in preventing cardiovascular events in high-risk patients. As a result, GLP-1s have become one of the American Diabetes Association’s recommended first-line therapies.

GLP-1s also promote weight loss by slowing the speed of stomach emptying, extending the feeling of a full stomach and curbing the appetite by sending signals to the brain.

Despite select FDA approvals, utilization trends show a substantial increase in the use of unapproved type 2 diabetes GLP-1 therapies for weight loss.2

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Our clinical position At Prime Therapeutics (Prime), we deliver next-generation pharmacy solutions, analyzing real-world data to gain a holistic view of the health care journey. Drug efficacy and safety are at the forefront of our evidence-based approach.

As we work with our clients to address the increasing demand for GLP-1s, we are committed to examining how GLP-1 use affects the total cost of care, long-term value and downstream impact on other health conditions. We are also monitoring studies that evaluate clinical outcomes.

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Long-term clinical considerations When used for weight management in individuals with preexisting cardiovascular disease (without type 2 diabetes), the GLP-1 semaglutide has been shown to improve cardiovascular outcomes. However, this is only a subset (less than 10%) of people with obesity without type 2 diabetes among commercially insured members. 3 It’s clear that more evidence is needed to determine the long-term health benefits of GLP-1s when used to treat obesity among individuals without preexisting cardiovascular disease.

• GLP-1s don’t work the same for everyone.

GLP-1s for weight loss in those without diabetes are typically appropriate for patients who: – Have a body mass index (BMI) of 30 kg/m2 or higher, or have BMI of 27 kg/m2 or higher with at least one weight-related comorbidity – Are compliant with their GLP-1 treatment – Can commit to and remain accountable for necessary lifestyle changes

Additionally, it’s important to recognize a few key considerations:

• Results must be monitored. Treatment with a GLP-1 should be stopped if at least 5% weight loss is not achieved in six months.

• The amount of weight loss associated with GLP-1s varies by agent. To date, tirzepatide (Zepbound), semaglutide (Wegovy) and liraglutide (Saxenda) have demonstrated greater potential for clinically meaningful weight loss in patients without diabetes compared to other GLP-1s.

• More time is needed. Multiyear studies will be required to determine long-term clinical benefits of GLP-1s for weight management in patients without diabetes.

GLP-1s for weight loss in those without diabetes are not yet cost effective, despite showing clinically meaningful weight loss.

Our real-world analysis In 2023, Prime published a real-world analysis of GLP-1 drugs for weight loss. We began by looking at integrated pharmacy and medical claims data across 16 million commercially insured members who started taking a GLP-1 between Jan. 1, 2021, and Dec. 31, 2021.

Members were required to have an obesity diagnosis, prediabetes diagnosis or a BMI of 30 kg/m2 or higher. Members were excluded from analysis if they had a prior diabetes diagnosis or diabetes drug therapy.4 Our Year-1 analysis found drug adherence was poor, with just 32% of individuals persisting on GLP-1 therapy for one year, dropping to 15% at the end of two years. There was also a substantial increase in health care costs in the first year — at $6,994 per person compared to matched controls.⁵ Among individuals who persisted with therapy during the first year, the increase in costs was even higher at $15,034, compared to matched controls.⁶ During the second year, the GLP-1 group experienced an average of $4,206 higher cost of care per person compared to similar members not taking a GLP-1 drug for obesity.⁵ The group persisting two years on GLP-1

8%

therapy had a $13,085 higher cost of care per person compared to matched controls.⁶ Furthermore, we saw no reduction of medical events over the first two years of therapy among individuals newly initiating GLP-1s for weight loss treatment without diabetes.7 Our Year-3 analysis found only 1 in 12 remained on a GLP-1 drug for obesity after three years. Among those initiating Wegovy, 1 in 7 individuals remained on therapy.8 GLP-1 supply chain issues, including product shortages, were largely resolved in 2024 and likely explain the change in persistence.

Improved GLP-1 dose escalation, side-effect management and lifestyle management programs have also contributed. The extremely low, three-year GLP-1 obesity treatment persistence seen among individuals initiating in 2021 may not be reflective of the current state — one-year persistence nearly doubled between 2021 and first quarter 2024. Additional research is still needed to understand reasons for treatment discontinuation and long-term cost-effectiveness.

persistence on GLP-1 therapy for obesity without diabetes after three years8

One-year therapy persistence on high-potency, obesity-indicated GLP-1 products⁸ semaglutide (Wegovy) Therapy initiated Persistence rate 2021

33.2%

2022

34.1%

2023

40.0%

Q1 2024

62.7%

tirzepatide (Zepbound) Therapy initiated Persistence rate 2021

N/A

2022

N/A

2023

64.0%

Q1 2024

62.6%

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“GLP-1 drugs and their use for weight loss have taken the health care industry by storm, but several issues must be resolved, including how to ensure that those who may benefit most have access while maintaining overall pharmacy benefit affordability.

While we hope to see additional data to refine our guidance, health plans should consider programs to help adherence in order to avoid medication waste and comprehensive therapy plans — which include diet and exercise — to help people on their weight loss journey.”

David Lassen, PharmD Chief Clinical Officer

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“Prime remains committed to studying the impact of GLP-1s for the foreseeable future because clients and patients deserve to make informed decisions, and our real-world data can help them do that,” said Marci Chodroff, M.D., vice president and medical director at Prime. “The popularity of GLP-1 drugs as a treatment for obesity meets a sobering reality of poor adherence and high cost of care in the real world, and it may be quite some time before these measures and health metrics improve in any substantial way.”

Additional findings from the Year-2 study include an increased rate of acute pancreatitis among individuals taking a GLP-1 drug for obesity in the first year of therapy. Per the study data, researchers found one additional acute pancreatitis event per 250 people treated with a GLP-1.7 The findings indicate that individuals who do not have diabetes will see no medical cost offset in their GLP-1 treatment over two years. They can expect a total cost of care increase of $11,200 per individual at two years compared to matched controls not taking a GLP-1, at standard drug prices prior to discounts, with only 1 in 7 still taking a GLP-1 drug.

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Drug pipeline As innovative leaders in pharmacy, we exemplify our commitment to advancing health care by proactively managing a dynamic and robust drug pipeline. Beyond investigational GLP-1 therapies, FDA-approved GLP-1 therapies for diabetes and weight loss are being studied for other indications.

Additionally, multiple new molecular entities are being studied for both diabetes and weight loss, including oral GLP-1s for weight management.

Prime’s GLP-1 Pipeline Update focuses on the development of GLP-1s. It provides updates on new therapies in the pipeline, their potential clinical benefits, and the implications for treatment options and health care costs.

See our latest GLP-1 Pipeline Update

To proactively capture the emerging GLP-1 landscape, Prime publishes our GLP-1 Pipeline Update to provide a credible clinical snapshot of what’s on the horizon.

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GLP-1 prescriptions commercial population (PMPM) GLP-1 commercial book of business (BoB) = ~16M lives $29.15

Spend and trend $9.01

JANUARY 2022

MARCH 2025

GLP-1 costs and utilization continue to rise. In January 2022, we saw GLP-1 total per member per month (PMPM) cost at $9.01 across our commercial population. By March 2025, we saw a threefold increase to $29.15 PMPM. GLP-1 costs now account for 15% of the entire pharmacy benefit spend, and they’re growing at a faster rate than any drug category. More than 1 in 50 members had a GLP-1 claim in the first quarter 2025.9

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Assessing historical utilization and spend patterns, Prime forecasts that increasing GLP-1 weight loss utilization by just 1% of an insured population would drive more than an additional $10 in costs PMPM, totaling ~5% of a self-insured employer’s drug spend.10 What’s more, the Institute for Clinical and Economic Review (ICER) performed a costeffectiveness analysis at an annual wholesale acquisition price of $11,500–$14,000 for GLP-1 weight loss treatments. For weight loss associated with reduction in cardiovascular events and diabetes development avoidance over a lifetime, ICER found GLP-1 weight loss therapies are overpriced by almost double their expected value.11 Paired with our own analysis, these findings indicate GLP-1 weight loss products should have a pharmaceutical manufacturer, patient-centered, value-based arrangement with health plans or pharmacy benefit managers (PBMs) to ensure fair pricing.11

Forecast GLP-1 weight loss utilization

1% 5%

A 1% increase in GLP-1 use in an insured population

Would drive a 5% increase in a self-insured employer’s drug spend

$10+

Equaling more than a $10 increase in costs PMPM10

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Management strategies

At Prime, we use an evidence-based approach to GLP-1 management as we work with our clients to address the soaring demand for GLP-1 medications and the impact on total cost of care. We help our clients drive clinically appropriate use of GLP-1s through strategic utilization management.

Watch for counterfeits

Using integrated medical and pharmacy data, we deliver market-leading utilization and trend dashboards that include drugspecific GLP-1 forecasting to help clients stay ahead of the curve. Knowing a member’s diagnosis — whether it’s diabetes, obesity without diabetes, cardiovascular disease or sleep apnea — helps us identify utilization and cost risk.

risk of buying fake, unapproved

Our Core and Advanced Fraud, Waste and Abuse (FWA) product provides active monitoring for GLP-1 FWA through advanced analytics that tap into integrated medical and pharmacy data. Potentially problematic pharmacy, member and prescriber behavior is escalated for investigation and/or audit. Common findings have included misrepresented information on prior authorization (PA) documents and lack of adequate diagnosis or tried and failed therapies.

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The popularity of GLP-1s has also resulted in patients going outside of provider channels to buy these drugs, putting them at and sometimes contaminated medicine. Prime’s Special Investigations Unit (SIU) works to identify and prevent instances of FWA when it comes to these illegal counterfeits.

Learn more about counterfeits

Diabetic GLP-1 prior authorization (PA) program

Type 2 diabetes Our Gaps in Care® program targets members with cardiovascular disease and diabetes to recommend initiating or switching to a GLP-1 or sodium-glucose cotransporter-2 (SGLT-2) inhibitor that offers a proven cardiovascular benefit. While focused on diabetes management, these programs can also improve overall medication management for our members, including treating chronic conditions important to members with diabetes like hypertension and cholesterol.

Clinical automation captures patient diagnosis at point of sale Integrated medical claims data helps Prime capture patient diagnosis with an ICD-10 code at point of sale and bypass the need to submit a PA for preferred GLP-1s. This reduces member and provider abrasion as well as administrative costs associated with the PA process, while ensuring clinically appropriate use. PA bypass allows members to immediately get their medication at the pharmacy.

Diabetic GLP-1 PA criteria allows coverage for diagnosis of type 2 diabetes and excludes coverage for weight loss. This requires validation of trial/failure of guidelinesupported, cost-effective prerequisite therapies in appropriate patients as well as validation of a diabetes diagnosis with medical record documentation of ICD-10 diagnosis code.

Weight loss

How it works

DATA SOURCE

SYSTEM LOGIC

PA BYPASS

Integrates clientprovided medical data with claims platform

Replaces manual check for type 2 diabetes diagnosis

Allows for bypass of PA when diagnosis + prerequisite present

Weight loss drugs, including select GLP-1s, are a self-insured employer optional benefit election. As the PBM, Prime manages and administers formulary and benefits, but clients own formulary and benefit coverage decisions. Having PA criteria for weight loss agents ensures weight loss drugs, including GLP-1s, are used safely and effectively according to clinical guidelines and in conjunction with increased physical activity and behavioral modifications.

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Waste and misuse Our Concurrent Drug Utilization Review (cDUR) program was designed to help monitor and prevent medication waste, ensuring members aren’t taking multiple drugs with the same therapeutic purpose by targeting a subset of diabetes drugs with a high likelihood of waste and misuse. When a claim is rejected, the pharmacy is required to submit an override when appropriate (e.g., switching therapy, titrating, drug shortage).

Cardiometabolic health Cardiometabolic conditions can compound if left unchecked, causing serious and costly health problems down the line. We’re transforming cardiometabolic care, empowering members to take control of their health journey with comprehensive solutions.

Prime’s KeepWell™ product combines scientific advancements in medicine with compassionate support, delivering a comprehensive and caring approach to managing cardiometabolic health.

KeepWell is designed to support each member’s unique life and cardiometabolic health, helping members with conditions like obesity, diabetes, hypertension and high cholesterol.

Learn more about KeepWell

Identifying duplicative therapies Our HighTouchRx® program played a crucial role in identifying duplicative GLP-1 therapies, leading to $3.5M in total savings.

Read how Nicholas Friedlander, PharmD, and his team earned a Platinum Research Award in 2023 from the Academy of Managed Care Pharmacy for their work.12 As of June 2025, Prime has saved clients over $33 million in duplicate GLP-1 and/or dipeptidyl peptidase-4 (DPP-4) drug therapy through 3,920 successful HighTouchRx interventions.9

$3.5M in total savings

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intervention savings

Academy of Managed Care Pharmacy 2023 Platinum Research Award Learn more about HighTouchRx

The programs listed are not available to all clients.

Please check with your representative if you are interested in learning more.

$33M

HighTouchRx uses end-to-end data, paired with advanced clinical rules and machine learning, to identify nonoptimized drug use. Specialized pharmacists perform provider outreach to recommend drug therapy optimization. Then, following pharmacist intervention, Prime provides reporting that shows hard dollar savings.

HighTouchRx has successfully eliminated

AUTOMATED PHARMACY

MEDICAL CLAIMS REVIEW OPTIMIZATION

duplicative diabetic therapies, saving millions in the process, and continues to exist as a tool to optimize diabetic treatment regimens for members.

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Looking ahead The GLP-1 landscape continues to evolve.

As utilization increases in type 2 diabetes and weight management spaces and for new indications, it is important for savvy payers to develop a robust GLP-1 strategy.

Upcoming outcomes trials may offer insight into long-term benefits and safety. For now, GLP-1s are considered clinically efficacious but not cost effective.

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The path forward A thoughtful, nuanced and aligned approach will be the key to developing and maintaining a strong GLP-1 strategy.

Prime continues to prioritize benefit designs that align with the financial and health interests of our clients and their members.

We’ll continue to develop drug management strategies based on data, analysis and outcomes measurement.

1 About obesity. (2024, January 23). U.S. Centers for Disease Control and Prevention. https://www.cdc.gov/obesity/php/about/ 2 Ozempic, Wegovy, and Mounjaro: On- and off-label prescribing trends. (2023, June 26). Truveta. https://www.truveta.com/blog/research/ozempic-wegovy-and-mounjaro/ 3 Pisikian K., Gunderson B., Urick B.Y., Marshall L.Z., & Gleason P.P. (2024). Obesity with preexisting cardiovascular disease without diabetes: Current glucagon-like peptide-1 (GLP-1) agonist treatment prevalence among 16 million commercially insured members. AMCP Annual Meeting, April 2024. Journal of Managed Care and Specialty Pharmacy;30(Suppl 4a):E52 abstract. https://www.jmcp.org/doi/epdf/10.18553/jmcp.2024.30.4-a.s1 4 Gleason P.P., Urick B.Y., Marshall L.Z., Friedlander N., Qiu Y., & Leslie R.S. (2024). Real-world persistence and adherence to glucagon-like peptide-1 receptor agonists among obese commercially insured adults without diabetes. Journal of Managed Care and Specialty Pharmacy, 30(8), 860–867. https://doi.org/10.18553/jmcp.2024.23332 5 Prime Therapeutics releases poster on year-2 GLP-1 data (2025, March 31). Prime Therapeutics. https://www.primetherapeutics.com/documents/d/primetherapeutics/4085-b_amcp_spring25_glp1aallcosteffectiveness_r3-1-16 Prime Therapeutics releases poster on year-2 GLP-1 data (2025, March 31). Prime Therapeutics. https://www.primetherapeutics.com/documents/d/primetherapeutics/4085-a_amcp_spring25_pharmacykey_-glp1apersistentcosteffectiveness_r3-1-17 Prime Therapeutics GLP-1 research: Year-2 cost of care is $4,200 higher for patients with obesity. (2024, October 24). Prime Therapeutics. https://www.primetherapeutics.com/w/prime-therapeutics-glp-1-research-year-2-cost-of-care-is-4-200-higher-for-patients-with-obesity 8 Prime therapeutics’ leading research shows only 1 in 12 remain on a GLP-1 drug for obesity at three years. (2025, June 25). Prime Therapeutics. https://www.primetherapeutics.com/w/prime-therapeutics-leading-research-shows-only-1-in-12-remain-on-a-glp-1-drug-for-obesity-at-three-years 9Internal Prime analysis, 2025 10Internal Prime data, 2023; based on GLP-1 list prices at time of publishing, including, but not limited to, Wegovy and Zepbound 11 Obesity management. (2022, October 20). Institute for Clinical and Economic Review. https://icer.org/assessment/obesity-management-2022/#timeline 12 How Prime Therapeutics Tugged on the Reins of the Galloping GLP-1 Spend | AMCP Nexus 2023. (2023, October 20). Managed Healthcare Executive. https://www.managedhealthcareexecutive.com/view/how-prime-therapeutics-tugged-on-reins-of-the-galloping-glp-1-spend-amcp-nexus-2023

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