Evolution of GLP-1 Medications in Clinical Practice

Gut Linco Peptide-1 (GLP-1) medications have found a new “lease of life” as potential weight loss treatments. Originally developed to control blood sugar levels in people with diabetes by increasing the action of an incretin hormone, the effect of GLP-1 on insulin secretion, gastric emptying and appetite has led to their use for the treatment of overweight and obesity. Some GLP-1 receptor agonists, and the newer dual incretin agents, are now approved for this use or are being used “off label”. Clinicians have a number of issues to consider for individual patients as well as wider health system issues and public health policies to ensure appropriate use of these expensive medications and to weigh up their benefits and risks. Long term treatment and access to these medications are also important considerations.

Why it matters

There are now available on the market high dose forms of GLP-1 receptor agonists that could potentially revolutionize the treatment of two of the world’s most costly, common and harmful health diseases: type 2 diabetes and obesity. For decades, weight loss interventions have begun with lifestyle changes and/or over-the-counter or lower effectiveness prescription medications. Now, even more options are on the horizon for patients seeking weight loss with drugs.

First, the clinical benefits.

In addition to reducing body weight, substantial weight loss has been demonstrated to improve glucose levels, blood pressure, lipid profiles and reduce symptoms of knee pain and sleep apnea. Some of these medications have also been demonstrated to have cardiovascular benefits in diabetic patients reducing the risk of major adverse cardiovascular events in some trials. Clinicians have the advantage of using these medications in an attempt to decrease the symptoms of diabetes in the short term and the risk of cardiometabolic disease in the long term.

C. Third, implications for performance management.

Recent trials and long term data have shown large amounts of weight loss on medication, including with single agent semaglutide and the dual incretin tirzepatide. However patients tend to regain weight in part or in full upon discontinuation of medication. This is accompanied by a partial or complete reversal of some of the improvements in the cardiometabolic risks. Clinicians and patients must consider the need for continued therapy, the duration of treatment and strategies for ongoing follow up. Many specialists are now discussing the need for continued medication with their patients. In addition to medication, they offer programs that teach patients how to change their diet and lifestyle to help manage their condition on an ongoing basis.

Third, safety and tolerability require careful attention.

Gastrointestinal effects (nausea, vomiting, constipation, diarrhea) are common and increase with dose, but serious adverse events that are still under investigation include pancreatitis and gallbladder disease and acute kidney injury in the setting of dehydration. The FDA has added boxed warnings to the label for use in pregnancy and for patients with a personal or family history of medullary thyroid carcinoma. Reports of mental health effects and changes in eating behavior are anecdotal and considered a possible class effect. Individuals who take steroids may exhibit mood changes and/or disturbances in eating behavior. Some health professionals may find this information useful.

Fourth, equity and access.

New medicines cost a lot and work well — but the payer policies for them at hospitals and health systems around the country create a complicated web for patients hoping to use the medications. For example, some providers require patients who want semaglutide for obesity to have a minimum BMI, documentation of prior weight loss attempts, other health conditions that put them at higher risk for poor outcomes from being obese, or even that they be enrolled in a weight loss program. That means only the wealthy could gain access to these new medications, potentially exacerbating health disparities. Policymakers must consider not only the cost of these new medicines, but also the value to the population as they make decisions about coverage. They also may want to consider targeted coverage strategies to maximize value while limiting spending.

Fifth, implications for practice and policy.

Prescribers from primary care to endocrinology to obesity medicine are eager to learn how to safely and effectively incorporate these new drugs into their practice. This includes identifying the right patients for treatment, tapering up the dose and subsequently tapering down the dose, managing side effects as they arise, and coordinating with other providers on the medical team. Policy makers are interested in how health systems can update their formularies, physician guidance, and training programs in order to allow wider use of these promising medications without sacrificing crucial monitoring and follow up.

A: It may eventually become needed to honor public perception and demand ahead of clinical guidelines.

There has been much media attention on these medications and a consequent increase in patient enquiries regarding their use, including off label and unsupervised use. As healthcare professionals, we need to be well informed with accurate and evidence-based information regarding the realistic benefits and risks of these medications and the importance of appropriate medical management. When used appropriately as part of a comprehensive management plan for metabolic disease and obesity, these GLP-1 receptor agonists and related compounds are a major step forward. Now it is up to us to ensure the benefits are maximised and the harms minimised.

Who it affects

The effects of GLP-1 agents are not limited to patients with diabetes or those with head and neck cancer – providers from multiple disciplines and the general public will be affected.

Current evidence suggests that the main patient populations for whom GLP-1 therapies could be beneficial are those with type 2 diabetes, as well as the increasing number of overweight or obese patients. For diabetic patients, these therapies offer effective glucose lowering without the risk of hypoglycemia whether used alone or in combination with sulfonylureas or insulin. Patients who are obese would benefit from weight loss induced by high dose GLP-1 receptor agonists and GLP-1 dual agonists, improvement of symptoms of obesity and related conditions, and improvements in metabolic parameters. Thus, the patient could be simply obese or could have other weight related comorbidities, such as hypertension, dyslipidemia, sleep apnea, or prediabetes.

These individuals may include the patient’s primary care physician or endocrinologist who will be prescribing the medications and monitoring the patient for possible side effects.

The general practitioner (GP) is typically the doctor first approached by the patient to discuss their weight and metabolic risk. As such, the GP needs to have some basic skills to assess the patient, set realistic expectations, educate the patient as to the benefits and potential harms of weight loss, initiate treatment and manage side effects. In more complex cases, in those requiring combination therapy or long term follow-up the endocrinologist or obesity specialist would be involved.

Other specialists are affected too.

Health care professionals who need to understand the cardiometabolic effects of these medications and their impact on cardiovascular risk are primarily cardiologists. Health care professionals who need to counsel women of childbearing age about the effects of these agents on reproductive planning are obstetricians/gynecologists, given current recommendations to avoid use of these agents in pregnancy and the necessary duration of washout before conception. Mental health professionals may be involved in medical management of patients taking these medications for symptoms of depression, anxiety, or eating behaviors. Obstetricians, cardiologists, endocrinologists, primary care physicians, pharmacists, nurses, and dietitians, as well as other allied health professionals can play a role in educating patients and families, ensuring adherence to prescribed doses, facilitating management of medication dose and administration, and supporting healthy lifestyle choices.

The costs of health care and the way resources are allocated in health systems and health care payers have important consequences.

While the transition to widespread use of pharmacogenomics may result in large short term increases in drug expenditures that are potentially offset by long term cost savings, payers are beginning to develop coverage policies and prior authorization criteria for the use of several specific drugs. Consideration should also be given to plans and resources for workforce training and monitoring of treatment, including surveillance for adverse effects, as well as the development of laboratories and scheduling for follow-up tests.

These are the stakeholders for this batch of medications. The supply chain of the pharmaceutical medications are represented here as well as the various regulatory bodies.

The increased demand for cannabinoids to support the development of new products for the market has created several challenges including supply constraints, off label purchasing or diversion, and regulatory challenges. Regulatory bodies are monitoring post market safety signals generated by these products and have modified labeling or guidance as more information has become available. Public health agencies and professional medical and scientific societies will provide evidence-based information for safe use of these products.

What changes

• Practice patterns for GLP-1 medications are already shifting and further change is likely across clinical care, systems, and policy. Key areas of change include clinical pathways, monitoring practices, payment models, research priorities, patient education, and workforce development.
• Clinical pathways and guidelines. Expect more detailed, condition specific guidance to emerge as long term evidence accumulates. Clinicians should follow best practice protocols that define candidate selection criteria, stepwise dosing schedules, side effect management plans, and adjunctive strategies such as structured lifestyle programs. Clear protocols reduce inappropriate use and improve safety. Shared decision making tools help patients understand benefits, risks, and the likely need for long term follow up.
• Monitoring and safety practices. Routine baseline assessment prior to starting therapy should include a thorough history, screening for contraindications, measurement of weight and metabolic parameters, and review of current medications to reduce interactions. During treatment, structured follow up for side effects, hydration status, mood changes, and glycemic response is essential. Labs such as renal function and relevant metabolic markers should be measured as clinically indicated. Systems should track outcomes and adverse events to inform ongoing safety evaluation.
• Payment and access models. Policymakers and payers are experimenting with value based approaches to manage high cost therapies. Examples include step therapy that requires documented weight management attempts, requirement for enrollment in multidisciplinary weight support programs, or time limited coverage with reauthorization based on weight loss milestones. Some jurisdictions may negotiate prices or restrict indications. Equity focused policies are needed so that access does not become limited to higher income groups.
• Long term treatment planning. Given the propensity for weight regain after stopping therapy, clinicians and patients must plan for maintenance. This may include continued medication at the lowest effective dose, integrating behavior change programs, or transitioning to other therapies when appropriate. Research into combination approaches and strategies to sustain weight loss without indefinite medication is a priority.
• Research and evidence generation. Ongoing trials are comparing agents head to head, testing combination therapies, and assessing longer term safety and cardiovascular outcomes in broader populations. Real world data will help refine which patients benefit the most and inform deprescribing or maintenance approaches. Comparative effectiveness studies and health economic analyses will guide system level decisions.
• Education and workforce development. As demand grows, training programs for primary care, nursing, pharmacy, and allied health must include practical instruction on GLP-1 therapy. Counseling skills, side effect management, and coordinated care models will become core competencies. Telehealth and remote monitoring tools can extend capacity and support ongoing follow up.
• Public messaging and ethical considerations. Accurate public communication about realistic benefits, side effects, and the need for clinical supervision will be important to counter hype and reduce inappropriate self medication. Ethical questions include prioritization of access, use in younger populations, and marketing practices that may encourage non medical use. In conclusion, the evolution of [GLP-1 medications](/glp-1-medications-may-benefit-fatty-liver-and-weight-loss) represents a significant shift in how clinicians can treat diabetes and obesity. These agents offer powerful benefits for many patients but require careful candidate selection, thorough counseling, and coordinated care to manage safety, cost, and long term outcomes. Health systems, payers, and clinicians must work together to ensure equitable access, rigorous monitoring, and continued research so that these therapies are integrated responsibly into routine practice.

References:

https://pmc.ncbi.nlm.nih.gov/articles/PMC11940170/ https://www.yalemedicine.org/news/glp-1-medications-for-weight-loss-how-to-get-started