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The absence of safety and efficacy data for drugs in individuals with obesity in package inserts may compromise health outcomes.

Bruno Halpern, MD, PhD, a specialist in endocrinology and internal medicine and president of the Brazilian Association for the Study of Obesity and Metabolic Syndrome (ABESO), warned that this knowledge gap may lead to overdosing or underdosing, depending on how the drug is absorbed.

“For example, a patient undergoing chemotherapy who needs an exact dose may receive an insufficient amount, compromising their chances of cure and clinical recovery,” he said.

Halpern, who is also the president-elect of the World Obesity Federation for 2026, raised another concern: The risk of toxicity from the prolonged use of medications that remain bioavailable in individuals with obesity. For example, lipophilic drugs accumulate in adipose tissue, resulting in drug interactions.

Research Findings

A 2023 article in Current Obesity Reports emphasized the scarcity of data on the behavior of drugs in individuals with obesity. The authors noted that obesity affects pharmacokinetics and pharmacodynamics, delaying the onset of the effect or prolonging its activity.

This review article cited examples of drugs with modified effects in individuals with obesity.

• Brexpiprazole (antipsychotic): May take longer to reach effective concentrations
• Vortioxetine (antidepressant): Prolonged half-life, requiring longer intervals between switching medications
• Diazepam (anxiolytic): The active metabolite remains in the body for a longer duration after administration
• Micafungin (antifungal): Standard doses may prove ineffective
• Cefazolin (antibiotic): Poor penetration into fatty tissue, increasing the risk of infection
• Tacrolimus (immunosuppressant): Risk of overdose if the dose is based on total weight
• Levonorgestrel (emergency contraceptive): Reduced efficacy in women over 70 kg
• Vitamin D: May require higher doses due to “volumetric dilution”
• Ibuprofen: Higher doses may be required to achieve an analgesic effect in patients with obesity
• Posaconazole (antifungal): Indicated for patients with cancer and those who have undergone transplantation, it has a prolonged half-life in individuals with obesity, which can intensify drug interactions as it interferes with the metabolism of various drugs. The package insert does not warn physicians of these side effects.

Despite these findings, many healthcare professionals remain unaware of the differences in medication response, and both drug package inserts and clinical guidelines rarely provide specific guidance for this population group.

“Some medications have doses calculated per kilogram of weight, which can be problematic in individuals with obesity. Often, total weight does not reflect the appropriate dose, which should consider the ideal weight or an adjustment for lean body mass. This varies depending on how drugs are absorbed and stored in the adipose tissue. Very few physicians are aware of these details,” Halpern stated.

He added, “Bariatric surgery itself alters drug absorption, yet little information exists on how this process occurs after the procedure.”

Regulatory Oversight

According to a statement from the Brazilian National Health Surveillance Agency (ANVISA) sent to Medscape’s Portuguese edition, there is no specific regulation regarding the relationship between obesity and the safety and efficacy of medications. However, the 2023 guidelines (59 and 60) emphasize that clinical pharmacological evaluations should consider intrinsic factors such as weight, age, sex, and hepatic or renal impairment. Additionally, clinical safety assessments should examine whether these risk factors, including obesity, affect the drug safety profile.

Regarding package insert requirements, if clinical development identifies any relevant risks related to weight, age, sex, or other intrinsic or extrinsic factors (such as smoking or alcohol consumption), this information must be included in the “Warnings and Precautions” section for healthcare professionals or in the “What should I know before using this medicine?” section for patients.

ANVISA also emphasized that the package insert texts are reviewed and, when necessary, revised during the drug registration process. Any changes, particularly those related to efficacy and safety information, must be submitted for reevaluation by the agency.

Halpern described ANVISA’s response as procedural. While there are cases where specific considerations are made for individuals with obesity, he noted that such measures are not mandatory, similar to the approach taken by most international regulatory agencies. He believes this gap could harm the obese population, as medication doses have not been adequately tested for this group.

“I think ANVISA’s stance aligns with global practices, but not necessarily with what should be done. This is not a criticism but an observation: While obesity rates are alarmingly increasing worldwide, the science behind the issue, including regulatory issues, has not advanced at the same pace as the problem itself. Many drug studies, for instance, exclude patients with severe obesity,” Halpern argued.

Clinical Inclusion

A study in the Journal of Clinical Pharmacology highlighted that individuals with obesity are often excluded or underrepresented in clinical trials, despite constituting a large proportion of the global population.

Despite the high prevalence of obesity in the United States, there are no regulatory requirements for the inclusion of this subgroup in clinical trials for new drugs. The authors emphasized that such exclusion criteria limit the ability of healthcare professionals to treat patients appropriately.

The authors suggest that individuals with obesity be recognized as a “special population” in clinical trials, similar to children, older adults, pregnant women, and patients with renal or hepatic insufficiency. They also advocated for investing in research on the impacts of varying degrees of obesity on drug responses and the inclusion of obesity-specific data in package inserts as part of clinical pharmacology trials.

A joint statement titled “Joint Statement in Support of Closing Gaps in the Drug Approval Process and Drug Labeling for People with Obesity” was issued by several US health organizations, including the Obesity Action Coalition and The Obesity Society.

Currently, there are no regulatory requirements in the United States for testing new drugs in individuals with obesity during the approval process.

These organizations urged the US Food and Drug Administration (FDA) to make it mandatory to include individuals with obesity in clinical trials and update package inserts to reflect safety and efficacy data for these individuals and urged pharmaceutical companies to stop excluding them from clinical studies.

Greyce Lousana, veterinarian and executive president of the Brazilian Society of Clinical Research Professionals noted that research protocols define inclusion and exclusion criteria, and patients who do not meet these parameters are excluded. However, as with pediatric studies, new protocols can be developed to assess the safety and efficacy of treatments in different population groups.

The FDA, ANVISA, and other regulatory agencies currently recommend the inclusion of greater population diversity in clinical studies. However, Lousana noted that achieving this is not simple.

“To include individuals with diverse characteristics, the sample size must be significantly expanded. Although challenging, this process tends to increase the safety of the drug under evaluation,” she said.

Practical Solutions

ABESO does not have an official stance on including particular information for individuals with obesity in package inserts. However, the organization published, in partnership with the Brazilian Association of Emergency Medicine, a position statement on the care of these patients in emergency departments.

The document provides detailed guidelines for improving care for individuals with obesity in emergency departments, providing practical recommendations for physicians, managers, and policymakers. The goal is to ensure adequate, humane, and safe care during emergencies. The document also offers practical recommendations to address challenges in care, such as the need for larger blood pressure cuffs and imaging equipment compatible with the size and weight of people with obesity. This document highlights the importance of adjusting drug dosages based on the ideal, adjusted, or total weight, depending on whether the drug is lipophilic or hydrophilic.

“Sedatives, such as etomidate, and muscle relaxants, such as succinylcholine, that require specific doses,” explained Halpern. Antibiotics, anticoagulants, and vasopressors require careful consideration.

The document also emphasizes the need for professional training, including adapted physical examinations and respectful language — such as “person with obesity” instead of “obese” — combating weight stigma and bias, and fostering empathy in patient care.

Conclusion

As obesity rates increase, particularly among underserved populations, healthcare services must adapt to the proper infrastructure, trained professionals, and tailored protocols. Respect, empathy, and technical expertise are essential for improving clinical outcomes in these individuals.

Halpern concluded that “ignoring the effects of obesity in clinical research and practice compromises equity in medical treatment.”

This story was translated from Medscape’s Portuguese edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.