Note: this piece is an update to the 2024 article Integrating Weight Management in Primary Care, published in this journal, which outlined practical methods to initiating and monitoring patient-centered weight management in a primary care setting. This article specifically addresses the use of GLP-1 and GIP receptor agonists.
The availability and increasing popularity of glucagon-like peptide-1 (GLP-1) receptor agonist weight-loss medications is leading to a significant shift in the treatment of obesity. The indications for GLP-1 and Gastric inhibitory polypeptide (GIP) receptor agonists have expanded beyond diabetes and overweight/obesity treatments, now including the prevention of cardiovascular disease (CVD) and treatment of obstructive sleep apnea (OSA) in adults with obesity. Furthermore, improvements in other conditions – such as hypertension, dyslipidemia, metabolic dysfunction-associated steatotic liver disease (MASLD), and alcohol use disorder – have been reported, primarily through the mechanisms of appetite suppression and weight loss. As of 2023, semaglutide has become the top prescription medication in the U.S. by the overall drug spending, and this is likely to continue for the foreseeable future. However, the side effect profile is not insignificant: in addition to the common gastrointestinal side effects of nausea, vomiting, constipation, and diarrhea, more serious adverse effects are being reported, including, diabetic retinopathy complications, concerns about mental health and suicidal ideation, pancreatitis, hypoglycemia, gallbladder or biliary disorders, accidental overdose, and aspiration during anesthesia or sedation due to the delayed gastric emptying effect. As the gatekeepers of the health care system at the forefront of the obesity epidemic, primary care clinicians need to be well-equipped to provide safe and effective weight management care using GLP-1s.
Given the significant heterogeneity in response to obesity treatment, it is imperative to implement a patient-centered approach. That is to say, there is no one-size-fits-all solution and not everyone with obesity needs or desires GLP-1 treatment. Beyond meeting the general pharmacotherapy criteria for weight management, safely initiating GLP-1 requires careful consideration of each patient’s comorbidities, as well as their potential contraindications to the medication class, which includes gastroparesis, pancreatitis, hypersensitivity, and a personal or family history of multiple endocrine neoplasia or medullary thyroid cancer. For patients of childbearing potiential, despite the possible increase in fertility associated with weight loss, the FDA recommends discontinuing GLP-1s at least two months before a planned pregnancy due to perinatal safety concerns and the prolonged washout period. Additional factors such as access to the medications, their cost, insurance coverage, and patient preference should be considered before initiating GLP-1.
Medication alone is not enough
A comprehensive initial evaluation focused on weight management is of utmost importance for setting realistic goals and expectations from the outset, as well as establishing appropriate follow-up care. When initiating GLP-1s, the discussion should include proper injection techniques, dose adjustment plans, and monitoring for potential adverse effects and response, typically on a monthly basis during the active weight-loss phase. Patients should also be counseled on dietary changes that can mitigate GLP-1 side effects, such as reducing portion sizes, eating slowly and mindfully, limiting greasy and highly processed foods, avoiding late-night eating along with carbonated drinks and alcohol, and staying well-hydrated. In addition to taking medication, it is imperative to help patients implement lifestyle changes including healthy eating, stress management, adequate sleep, and regular physical activity. In particular, ensuring adequate dietary protein intake (60 g/day to 1.5g/kg/day) and incorporating resistance training can help prevent the 25 to 39 percent muscle loss associated with GLP-1 use.
Considerations for long-term weight loss
Obesity is a chronic and relapsing multifactorial condition that requires a multifaceted personalized treatment approach beyond the initial weight loss phase to ensure weight loss is maintained long-term. Studies investigating the effect of withdrawal of GLP-1 treatment have been mixed, with one showing that withdrawal of GLP-1 treatment can lead to a regain of two-thirds of the weight loss on average due to physiological and behavioral factors. However, another large observational study of Epic EMR data reported that 56 percent of patients maintained or achieved additional weight loss a year after discontinuing GLP-1s. This highlights the significant variation in individual responses to obesity treatment and the need for personalized treatment plans. Given that weight fluctuation for an individual (sometimes referred to as the yo-yo effect) has been linked to a greater risk for cardiovascular disease and all-cause mortality, lifetime lifestyle changes should be implemented and chronic pharmacotherapy should be considered for weight-loss maintenance with the lowest, safest, and most effective dose when indicated.
Beyond GLP-1s
While GLP-1s have been the most popular and effective pharmacotherapy for weight loss to date, with average weight loss ranging from 15 to 21 percent of the initial weight, it is essential for primary care providers to consider oral anti-obesity medications (AOMs) when GLP-1s are contraindicated, not tolerated, not preferred by the patient, or inaccessible due to shortages, cost, or insurance coverage. For example, Phentermine/Topiramate can lead to an average weight loss of 10 percent of body weight, with 70 percent of patients achieving the benchmark of clinically meaningful weight loss of 5 percent or more. Despite the recent decrease in metabolic bariatric surgery utilization, it remains the most effective treatment to date for obesity with an average weight loss of 20-35 percent. Primary care clinicians can play a critical role in recognizing the 2022 updated guidelines regarding access to weight-loss surgery outlining lower BMI criteria and implementing a stepwise, evidence-based approach to referring appropriate patients when indicated.
While there are challenges to fitting weight management into a busy primary care practice, it is possible to create a workflow and system that can allow clinicians to partner with patients through dedicated visits. Primary care providers are well-positioned to address the obesity epidemic through comprehensive and patient-centered approaches, including the safe and effective use of GLP-1s in the primary care setting.
This article was published as part of a series for Obesity for World Obesity Day, March 4, 2025. View the full Special Series for more articles and messages from the editors regarding language and content.
Special Series
About the author
Wudeneh Mulugeta, MD, MPH, is a primary care physician board-certified in internal medicine, preventive medicine, and obesity medicine. He is a faculty member at Harvard Medical School and a fellow of the American College of Preventive Medicine and the American College of Physicians.
**Feature photo obtained with a standard license on Shutterstock.
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