Clinical Perspectives: The evolution of GLP-1s

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CLINICAL PERSPECTIVES

The evolution of GLP-1s

Developing a holistic, individualized strategy to capitalize on opportunities and outcomes

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INTRODUCTION

Drugs classified as glucagon-like peptide-1 (GLP-1 receptor agonists have historically been used to manage type 2 diabetes in part due to their effectiveness in preventing cardiovascular events. As a result, GLP -1s have become one of the American Diabetes Association’s recommended first-line therapies.

Demand for GLP -1s has soared in the past two years, which may be linked to a few factors. According to the Centers for Disease Control and Prevention, more than 41% of U.S. adults are obese. Wegovy (injectable semaglutide) also received FDA approval in June 2021 for chronic weight management as an adjunct to a reduced calorie diet and increased physical activity. A number of social media influencers and celebrities have credited GLP -1 therapies for aiding in their weight loss, which sparked a seismic increase in requests for GLP -1 prior authorizations (PAs) and created shortages for some medications, making them unavailable for diabetic patients in need.

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

How GLP-1s work

GLP -1s may be taken orally or subcutaneously. 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).

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

OUR CLINICAL POSITION

At Prime Therapeutics (Prime), we deliver nextgeneration pharmacy solutions, analyzing realworld 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 their use affects the total cost of care, their long-term value and their downstream impact on other health conditions. We are also monitoring studies that evaluate clinical outcomes.

Long-term clinical considerations

When used for obesity in individuals with preexisting cardiovascular disease (without type 2 diabetes), GLP -1 semaglutide has been shown to improve cardiovascular outcomes. However, this is only a subset (less than 10%) of obesity without type 2 diabetes among commercially insured members.2 More evidence is needed to determine their long-term health benefits when used to treat obesity among individuals without preexisting cardiovascular disease.

Additionally, it’s important to recognize some key considerations:

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

• GLP-1s don’t work the same for everyone. GLP-1s for weight loss in those without diabetes typically work in patients who:

Have a BMI of 30 or higher

Are compliant with their GLP -1 treatment Can commit to and remain accountable for necessary lifestyle changes

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

• 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

Prime analyzed integrated pharmacy and medical claims data across 16 million commercially insured members to identify 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 body mass index of 30 or higher. Members were excluded from analysis if they had a prior diabetes diagnosis or diabetes drug therapy.

Our analysis found adherence to these drugs was poor, with just 27 % of individuals adherent to GLP -1 therapy during their first year of therapy. What’s more, there was a substantial increase in health care costs in the first year at $7,727 per person. And, among GLP -1-adherent individuals, the increase in costs was even higher, double that of the matched controls, at $13,218 higher total cost of care per person.

$7,727

adherence after one year 27% increase in health care costs in the first year

$13,218

higher total cost of care per person for GLP-1 adherent individuals

“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 to avoid medication waste and comprehensive therapy plans which include diet and exercise — to help people on their weight loss journey.”

DRUG PIPELINE

In this pivotal era of pharmaceutical innovation, we exemplify our commitment to advancing health care by our proactive management of a dynamic and robust pipeline. This section serves as a comprehensive exploration of current GLP -1 therapies and identifies what is on the horizon in this space.

The pipeline for GLP -1 therapies is robust. There are investigational GLP -1 therapies in the pipeline as well as GLP -1 therapies that are FDA approved for diabetes and weight loss that are being studied for other indications. In addition, multiple new molecular entities are being studied for both diabetes and weight loss. The investigational agents listed are not all-inclusive and are subject to change, given the fluid nature of the pipeline.

5,856 ($6.86)

9,950 ($17.96)

GLP -1 costs and utilization continue to rise. In August 2021 we saw 5,856 GLP -1 prescriptions filled across our commercial population, with total per member per month (PMPM) cost at $6.86. Fast forward to July of 2023 and the number of prescriptions nearly doubles reaching 9,950 and driving a total of $17.96 PMPM.2

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.4

What’s more, at an $11,500–$14,000 annual wholesale acquisition price for GLP -1 weight loss treatments, the Institute for Clinical and Economic Review (ICER) cost-effectiveness analysis identified that GLP -1 weight loss therapies are overpriced twofold to their expected value in weight loss associated reduction in cardiovascular events and diabetes development avoidance over a lifetime. The ICER findings, coupled with Prime's analysis, indicate GLP -1 weight loss products should have a pharmaceutical manufacturer, patient-centered, value-based arrangement with health plans or PBMs to ensure fair pricing.

Equaling more than a $10 INCREASE IN COSTS PMPM4 $10+

MANAGEMENT

STRATEGIES

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

We deliver enhanced utilization and trend dashboards for GLP -1s, inclusive of drug-specific forecasting to help clients stay ahead of the curve. They can elect to apply utilization management to formulary drugs in order to limit the indications for which coverage is granted. Enhanced utilization management strategies include validation processes and use of integrated medical data.

Our Core & Advanced Fraud, Waste and Abuse (FWA) product provides active monitoring for GLP -1 medication FWA through advanced analytics that use 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 PA documents and lack of adequate diagnosis or tried and failed therapies.

DIABETIC GLP-1 PRIOR AUTHORIZATION (PA) PROGRAM

Clinical edit automation captures patient diagnosis at point of sale

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

HOW IT WORKS

SOURCE

Integrates client-provided medical data with claims platform Replaces manual check for type 2 diabetes diagnosis

Allows for bypass of PA when diagnosis + prerequisite present

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 SGLT-2 that offers a proven cardiovascular benefit. While focused on diabetes management, these programs can also improve overall medication management for our members, including other therapies important to members with diabetes like hypertension and cholesterol.

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 guideline-supported, costeffective prerequisite therapies in appropriate patients as well as validation of a diabetes diagnosis with medical record documentation of ICD -10 diagnosis code.

Weight loss

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. Weight loss agents PA criteria ensures weight loss drugs, including GLP -1s, are used safely and effectively according to clinical guidelines and in conjunction with increased physical therapy and behavioral modifications.

Our HighTouchRx® product uses end-to-end data, paired with advanced clinical rules and machine learning, to identify non- optimized drug use. Specialized pharmacists perform provider outreach to recommend drug therapy optimization. Then, following pharmacist

intervention, we provide reporting that shows hard dollar savings. HighTouchRx has successfully eliminated duplicative diabetic therapies, saving millions in the process, and continues to exist as a tool to optimize diabetic treatment regimens for members.

The programs listed are not available to all clients. Please check with your representative if you are interested in learning more.

LOOKING AHEAD

As the GLP -1 landscape continues to evolve, with utilization increasing in the type 2 diabetes and weight loss spaces, it will become ever more important for savvy payers to develop a robust GLP -1 strategy. Upcoming cardiovascular outcomes trials may potentially offer insight into long-term benefits. However, currently, GLP -1s are considered clinically efficacious but not cost effective.3

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.

Data, analysis and outcomes measurement will continue to serve as the foundation for all of our rug management strategies.

Given the trend and spend seen in the market and the need for a comprehensive weight loss solution, we are building an integrated weight loss product and lifestyle program that will integrate with customer benefit elections and support members on their wellness journey. This holistic cardiometabolic product will align with our formulary and clinical program strategy to deliver results to our customers and clinical outcomes for our members.

1 Obesity is a common, serious, and costly disease. (2022, July 20). Centers for Disease Control and Prevention. https://www.cdc.gov/obesity/data/adult.html

2 Internal Prime analysis, 2023

3 (n.d.). CTG Labs - NCBI. https://www.clinicaltrials.gov/

4 Internal Prime analytics, 2023, based on current GLP-1 list prices including, but not limited to, Wegovy and Zepbound

5 Obesity management. (2022, October 20). ICER. https://icer.org/assessment/obesity-management-2022/#timeline

7426-C 09/24 © 2024 Prime Therapeutics LLC

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