Because GLP1 receptor agonists (GLP1RA) delay gastric emptying, questions have been raised as to whether they have the potential to impair the activity of various oral medications absorbed primarily in the duodenum or small intestine. With GLP1RA use exploding, it makes sense to ask these questions.
Calvarysky, Dotan, Shepshelovich and colleagues surveyed the literature for answers to these questions, and published their findings in Drug Safety in January 2024.
The authors systematically reviewed the medical literature for evidence of interactions between oral medications (excluding oral hypoglycemics) and injectable GLP1RAs. Primary outcomes included these pharmacokinetic parameters: maximum plasma concentration (Cmax), time to maximum plasma concentration (tmax) and area under the curve (AUC). Pharmacodynamic parameters, including international normalized ratio (INR) for warfarin, lipid levels for statins, and gonadotropins or progesterone levels for oral contraceptive products were also investigated.
Warfarin
Coadministration of warfarin with a GLP1RA resulted in delayed tmax compared with warfarin alone, consistent with GLP1RA-associated gastric emptying. Minor differences were noted for Cmax and AUC, but generally not considered to be clinically important. Pharmacodynamic studies resulted in similar INR values at tmax and AUC for subjects with and without GLP1RA, suggesting clinical insignificance. Warfarin dose adjustments are not thought to be necessary with coadministered GLP1RA.
Combined Oral Contraceptives (COC)
Administration of COCs with GLP1RA resulted in reduced Cmax and delayed tmax for both the estrogen and progestin components. Ethinyl estradiol AUC was similar between groups, and AUC for the progestin ingredient was either unaffected or resulted in up to 20% higher mean exposure, generally not considered to affect safety or efficacy. Dose adjustments for COCs are not recommended with GLP1RA coadministration.
Acetaminophen
Similarly, acetaminophen, when coadministered with GLP1RA, resulted in decreased Cmax and delayed tmax, but a bioequivalent AUC, indicating similar overall exposure. Acetaminophen dose adjustments are not considered to be necessary with concomitant GLP1RA therapy.
Statins
Statins are often coadministered with GLP1RAs for patients with diabetes, dyslipidemia and obesity. As expected, reduced Cmax and delayed tmax were observed for simvastatin, atorvastatin, pravastatin, lovastatin and fluvastatin. Notably, AUC decreased for atorvastatin when used with dulaglutide and albiglutide, but atorvastatin is also known to exhibit >30% pharmacokinetic variability even without GLP1RA coadministration. Therefore, the AUC reductions observed with dulaglutide and albiglutide were deemed clinically insignificant. Furthermore, statin recipients in Phase 3 trials for exenatide showed comparable lipid lowering effects to subjects in the placebo arm of the trial. The groups also had no difference in the number of participants requiring statin dose increases. Hence, statin dose adjustments are thought to be unnecessary with GLP1RA therapy.
Angiotensin-Converting Enzyme Inhibitors (ACEI)
ACEI are also commonly coadministered with GLP1RAs. All changes in pharmacokinetic parameters were minor and clinically insignificant in the studies surveyed. Furthermore, the pharmacodynamic response, measured by 24-h ambulatory mean blood pressure, was not affected by GLP1RA therapy. Therefore, ACEI dose adjustments are likely not necessary when given alongside GLP1RAs, but blood pressures should be routinely monitored throughout therapy, as usual.
Erythromycin
A very small (n=9) study investigating the effects of prokinetic agents (metoclopramide, domperidone, cisapride, and erythromycin) on GLP1RA users. Erythromycin was observed to mitigate GLP1RA-mediated slowed gastric motility, and the associated postprandial antihyperglycemic effects of the GLP1RA. The other prokinetic drugs did not exhibit the same effects. Until the results of this study are replicated, it may be advisable to avoid erythromycin in GLP1RA users.
The FDA approved 2 MORE options for our GLP1-RA toolkit in March, specifically for weight reduction. This report will focus on the new HIGH DOSE WEGOVY, as it is already available via pharmacy wholesalers. Next month we will focus on the new Oral GLP-1RA, Orforglipron, which is approved but not yet available.
| Drug | Indication by Brand Name: | % Change in body weight* | Available Doses |
|---|---|---|---|
| Dulaglutide | Trulicity® - T2DM, ASCVD | AWARD-11 ~ 3-5% | WEEKLY INJECTION: 0.75---1.5---3---4.5 mg |
| Liraglutide | Saxenda® – Obesity Victoza® – T2DM, ASCVD | SCALE trial ~8% | DAILY INJECTION: 0.6---1.2---1.8---2.4---3mg |
| Semaglutide | Ozempic®-T2DM,ASCVD, & CKD (PAD pending) Wegovy®- Obesity, ASCVD, MASH (HFpEF pending) | STEP-1 trial: ~15% @ 2.4mg STEP-UP trial: ~ 19% @ 7.2 mg | WEEKLY INJECTION: Ozempic: 0.25---0.5---1---2mg Wegovy: 0.25---0.5---1---1.7---2.4---7.2 mg (HD) |
| Semaglutide ORAL FORMULATION | Rybelsus® - T2DM Wegovy®- Obesity | OASIS-4 trial: ~13.5% | DAILY ORAL: Rybelsus: 3---7---14mg Wegovy: 1.5---4---9---25mg (HD) |
| Tirzepatide (GIP/GLP-1RA) | Mounjaro® - T2DM Zepbound® - Obesity, & OSA | SURMOUNT-1 trial: ~21% | WEEKLY INJECTION: 2.5---5---7.5---10---12.5---15mg |
*based on respective clinical trials
References
Novo Nordisk. FDA approves Novo Nordisk's new Wegovy HD injection, delivering the highest weight loss to date for a Wegovy injection, adding to its already expansive clinical profile. March 19, 2026. Accessed March 26, 2026. https://www.prnewswire.com/news-releases/fda-approves-novo-nordisks-new-wegovy-hd-injection-delivering-the- highest-weight-loss-to-date-for-a-wegovy-injection-adding-to-its-already-expansive-clinical-profile-302718982.html
Novo Nordisk. Semaglutide 7.2 mg s.c. achieved 20.7% weight loss in the STEP UP obesity trial, and 18.7% regardless of treatment adherence. Novo Nordisk. January 17, 2025. Accessed March 26, 2026. https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=915087
IPD Analytics. Rx Brief: Endocrinology. FDA Approves New Higher Dose of Wegovy. April 2026
Package inserts accessed April 9, 2026:
The Food and Drug Administration (FDA) recently issued a warning letter to Novo Nordisk regarding improper reporting of potential adverse reactions associated with some of their products, including their glucagon-like peptide-1 receptor agonists (GLP-1 RAs) semaglutide and liraglutide. The issue was highlighted in a recent USA Today article, as well as other media sources, and has likely caused some patients to have concerns regarding the overall safety of these medications.
The FDA cited Novo Nordisk for failing to adequately report certain adverse events associated with its GLP-1 products within required timelines. The findings stemmed from an FDA inspection in early 2025; subsequent to the visit, a large spike in side effect reports was made by the company a few months later in July. Within one week during that month, almost 11,000 side effect reports were submitted, with greater than 1800 being considered as serious (typically such reactions are to be reported to the FDA within 15 days). More specifically, the FDA noted five cases where patients either experienced a stroke, considered suicide, or died. In addition, they noted that internal policy allowed the company’s call center operators to dismiss side effect reports if either the patient and/or medical provider didn’t feel the issue was the result of the drug being taken. It is important to note that the reports do not have to prove causality, but rather that the reported “event” occurred while a patient was taking the medication. While the agency did not call for removal of these medications from the market or labeling changes, the letter raises concerns about the completeness and timeliness of safety data being communicated to regulators.
GLP-1 receptor agonists, including semaglutide and liraglutide, have demonstrated substantial benefits in improving glycemic control, promoting weight loss, reducing cardiovascular risk, and potentially helping in numerous other health condtions in select populations. However, they are also associated with known adverse effects such as gastrointestinal intolerance, gallbladder disease, and rare but serious risks like pancreatitis and potential thyroid related cancer diagnoses. Post-marketing surveillance plays a critical role in identifying less common or delayed adverse outcomes that may not have been fully captured in clinical trials.
As the use of GLP-1 therapies continues to expand, the integrity of safety monitoring systems becomes increasingly critical. For practicing family physicians, this warning letter serves as a timely reminder to remain vigilant when prescribing these agents. Clinicians should continue to counsel patients thoroughly on potential side effects, monitor for emerging symptoms, and report suspected adverse events through the FDA’s MedWatch program. Accurate and timely reporting from frontline providers is essential to ensure that regulatory agencies maintain a comprehensive understanding of a drug’s safety profile.
The Drug Enforcement Agency (DEA) and the Wisconsin Department of Justice (DOJ) will be sponsoring another prescription drug disposal day on Saturday, April 25th, 2026. This free, anonymous event provides people the opportunity to safely dispose of unwanted, unused, or no longer needed medications.
Some guidelines for those wanting to dispose of unwanted medications through this event include:
Both the DEA and Wisconsin DOJ have links promoting the drug disposal day, including the ability to search for participating locations based upon city, county, or zip code. You can find more information by following the links below:
The good news is that if an individual misses one of these organized “take back” days, search mechanisms exist to locate permanent drug disposal boxes within Wisconsin that are always available to patients. Click here to be connected with this helpful resource!
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.
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