The Food and Drug Administration (FDA) recently issued a Drug Safety Communication requesting that manufacturers of certain glucagon-like peptide-1 agonists (GLP-1RA) remove product labeling that discussed risks of suicidal ideation and behavior (SI/B). The specific products identified included Saxenda (liraglutide), Wegovy (semaglutide), and Zepbound (tirzepatide), all of which are approved for use in the treatment of obesity.
Specific product labeling regarding SI/B was originally included with these products when they were initially approved for use. Such labeling is also found on the labeling of other weight loss medications, and the FDA’s communication noted that the warning was based on reports of observed events with a “variety of older medications used or studied for weight loss.” It should be noted that labeling of GLP-1RA medications approved for use to improve glycemic control do not contain such SI/B warnings. With these changes, the FDA notes that labeling will be consistent across all approved GLP-1RA medications.
The FDA notes that their decision to take this recent action was based upon an extensive review of available data regarding actual GLP-1RA use. Although they mention that in their initial review of the data no evidence of SI/B associated with GLP-1RA use was found, they ultimately made the decision to perform a comprehensive meta-analysis of clinical trials due to a small number of case reports of SI/B. This meta-analysis included 91 placebo-controlled clinical trials with 107,910 participants (60,338 who received active treatment with GLP-1RAs and 47,572 who were on placebo). The results of the study revealed no statistically significant increase in SI/B risk or other significant psychiatric adverse effects (anxiety, depression, irritability, or psychosis) among patients treated with GLP-1RAs versus those on placebo.
They further go on to describe a retrospective cohort study they performed comparing risk of intentional self-harm between patients with type 2 diabetes mellitus who newly initiated GLP-1RAs and sodium-glucose cotransporter 2 inhibitors (SGLT2i). The study utilized administrative healthcare data claims from the FDA Sentinel System. The study involved over 2 million users, split almost equally between users of GLP-1RAs and SGLT2is, from October 1, 2015, through September 20, 2023. Baseline confounders were noted to be controlled. Their analysis showed no increased risk of self-harm in either treatment group. In addition, they noted finding no increased risk in the subgroups of patients with both type 2 diabetes mellitus and obesity.
Based on their extensive efforts, they noted that, “Our review concluded that the totality of these studies does not support a causal relationship between the use of GLP-1 RAs and the occurrence of SI/B.” It was with this conclusion that the FDA has requested the removal of SI/B labeling from the GLP-1RAs mentioned above.
As with any approved medication, the FDA requests consumers and health care providers to report adverse effects and/or safety issues that are encountered in practice. They indicate in their communication to report side effects with GLP-1RA use (or other medications) to the FDA MedWatch program.
Question from the clinic: “I heard there is a new oral GLP1-RA available for weight loss… can you please tell me more about it?”
Answer: The “new oral” simply a new dose/new marketing for the oral semaglutide that has been available since 2019. (see Pharm Aid May 2019). However, there is another oral GLP-1 in development that could be approved in 2026 (orforglipron)
Details:
We all know how complicated Medicare prescription drug pricing has become in recent years. Efforts to help Americans manage drug costs, while beneficial to be sure, have inadvertently muddied the waters.
To complicate matters further, copays and deductibles often change annually. Many patients experience sticker shock when they visit the pharmacy in January each year, as copay/coinsurance structures change with the beginning of the new calendar year and deductibles reset to $0. Often this results in panicked phone calls to physician practices or pharmacies, seeking affordable options.
Clinical Pharmacy Practitioner in Primary Care
Mike Grunske, PharmD, BCPS
Mike Grunske is a Board-Certified Pharmacotherapy Specialist (BCPS). Mike transitioned his practice to the Clement Zablocki VA Medical Center where he has since practiced in the Primary Care Clinics as a Clinical Pharmacist Practioner. Within this role, his practice involves direct care and management of patients’ medication regimens. He has worked as an active preceptor for both pharmacy students and residents throughout his entire career. Mike is also Past-President and former Foundation Chair of the Pharmacy Society of Wisconsin (PSW).
Mike is married to a fellow PharmAid contributor (Vanessa Grunske). Together they have a teenage daughter and son. He enjoys traveling with his family, attending his kid’s cheer, baseball, and basketball events, and spending any available leftover time running and hunting.
Pharmacist at Advocate Aurora Health
Vanessa Grunske, PharmD, BCACP
Vanessa practices with Advocate Aurora Health in Milwaukee, where she sees patients at Aurora Sinai Medication Management Clinic and maintains a dispensing practice at St. Luke’s Medical Center. Board-certified in ambulatory care pharmacotherapy, her practice interests include diabetes, hypertension, smoking cessation, geriatrics, improving health literacy, and medication adherence. She particularly enjoys and spends a good share of her work hours teaching and mentoring pharmacy students, family medicine residents and pharmacy residents.
She and her husband, Mike, live in the Milwaukee area with their two teenage children. In her free time, she enjoys cooking, baking, visiting our national parks with her family or relaxing on a beautiful Caribbean beach.
Professor at Concordia University Wisconsin School of Pharmacy
Beth Buckley, PharmD, CDCES
Beth Buckley, PharmD, CDCES (Certified Diabetes Care and Education Specialist), is a Professor of Pharmacy Practice at the Concordia University Wisconsin School of Pharmacy, where she has a teaching role within all years of the curriculum with a focus on Applied Patient Care Skills Lab, Diabetes Pharmacotherapy, and electives in the areas of diabetes and wellness. Her current role is ambulatory care pharmacist where she works with a Collaborative Practice Agreement to provide chronic disease state management within a primary care clinic.
When not working, she enjoys reading, gardening, traveling with her husband, volunteering within the community, and active fun: hiking, biking, dog walking, practicing yoga, mindfulness, and living with intention and gratitude.
Disclaimer: The Wisconsin Academy of Family Physicians (WAFP) has entered into a business relationship with Pharm Aid to offer our members discounts and exclusive savings. This or other affinity program relationships presented by the WAFP in no way implies a WAFP endorsement of the program, supplier, or vendor.
