Table of Contents
Introduction
Obesity is one of the most serious and costly public health problems of our time. It affects more than one billion people worldwide and is linked to diabetes, heart disease, fatty liver disease, cancer, and shortened life expectancy. For many individuals, obesity is not only about weight gain but also about how the body regulates hunger, hormones, and energy use. Over the years, doctors and scientists have recognized that lifestyle changes such as diet and exercise, while important, are often not enough on their own to produce or maintain major weight loss. This reality has led to strong interest in medical treatments that can help people lose weight safely and keep it off long-term.
For decades, the field of obesity pharmacotherapy struggled with limited options. Many earlier weight-loss medications worked by suppressing appetite in the brain, but some caused concerning side effects or were only modestly effective. Others were withdrawn from the market due to safety issues. This created a gap between the growing need for effective therapies and the available tools for clinicians. In the past few years, however, a new class of medications—known as incretin-based drugs—has transformed diabetes care and, more recently, obesity management. These medications work by mimicking natural gut hormones that help control appetite, slow digestion, and influence how the body handles sugar and fat.
One of the most promising among them is tirzepatide, a once-weekly injection developed initially to treat type 2 diabetes. Tirzepatide acts on two hormone receptors at once: glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). By combining these effects, tirzepatide helps reduce appetite, improve blood sugar control, and promote substantial weight loss. Early clinical trials, such as those in the SURPASS and SURMOUNT programs, showed that patients could lose more than 20% of their body weight with tirzepatide—results that were previously seen only with bariatric surgery. These trials set the stage for further research and real-world studies to confirm how well the drug works outside controlled environments.
This is where the recent JAMA publication on tirzepatide becomes a turning point. The Journal of the American Medical Association (JAMA) is one of the world’s most respected medical journals. Its publications often influence how doctors and policymakers think about new treatments. The JAMA paper on tirzepatide analyzed large sets of patient data to compare its effectiveness and safety against other obesity and diabetes medications, including semaglutide, another GLP-1 agonist that gained widespread use under brand names such as Wegovy and Ozempic. The study’s findings showed that tirzepatide led to greater average weight loss than semaglutide and confirmed its potential as a major advancement in obesity care.
This new evidence matters for several reasons. First, it confirms that tirzepatide’s results are not just limited to clinical trials, where patients are carefully selected and monitored, but also extend to broader, more varied real-world populations. Second, it highlights that pharmacologic treatment for obesity has entered a new phase—one where weight reduction of 15–20% or more is achievable with medication alone. This level of effectiveness has the potential to reduce the long-term health risks of obesity-related conditions dramatically. Third, the publication adds credibility and visibility to the concept of treating obesity as a chronic disease that requires long-term management, rather than a short-term diet or lifestyle effort.
The importance of this development extends beyond individual patient outcomes. Health systems, insurance providers, and policymakers are now forced to reconsider how obesity care is delivered and funded. If medications like tirzepatide can safely help millions of people achieve sustained weight loss, this could reshape everything from preventive care strategies to economic models for chronic disease management. For physicians, the JAMA publication offers an evidence-based foundation for prescribing tirzepatide not only for people with diabetes but also for those living with obesity without diabetes. For researchers, it raises new questions about the mechanisms behind dual-hormone therapies and how future generations of similar drugs might perform even better.
In this article, we will explore how the JAMA publication on tirzepatide changes the landscape of obesity treatment. We will explain what the study found, how it was conducted, and what it means for patients and clinicians. We will also discuss the safety profile, the potential benefits and risks, the differences between tirzepatide and other treatments, and the future of obesity management as this new evidence reshapes clinical practice. By the end, readers should understand why the JAMA findings are considered a milestone and how they might influence the way obesity is treated in the years ahead.
Overview of the JAMA Publication on Tirzepatide
Obesity is one of the biggest public health challenges in the world today. It affects hundreds of millions of people and increases the risk of many diseases such as type 2 diabetes, heart disease, stroke, and some cancers. For decades, doctors have struggled to find medications that lead to meaningful, long-term weight loss without serious side effects.
Tirzepatide, a once-weekly injection, has drawn strong attention because of its powerful effects on both blood sugar control and weight reduction. It works by acting on two hormones in the body—GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide)—that help regulate appetite, blood sugar, and digestion. Earlier studies, including the SURMOUNT and SURPASS trials, showed promising results for tirzepatide in patients with obesity and type 2 diabetes.
The JAMA (Journal of the American Medical Association) publication was designed to take a deeper look at how tirzepatide performs in the real world and how it compares with another well-known medication, semaglutide, which is already used widely for weight loss and diabetes. Researchers wanted to understand whether the strong weight loss seen in clinical trials could also be achieved in everyday clinical practice.
Study Design and Methods
The JAMA study used large-scale, real-world data to compare tirzepatide and semaglutide in adults who were overweight or obese. The data came from electronic health records (EHRs) and included people treated in primary care or endocrinology settings.
Researchers included thousands of adults who had recently started either tirzepatide or semaglutide for weight management or type 2 diabetes. The study design was observational, meaning participants were not randomly assigned to one drug or the other. Instead, the researchers used advanced statistical techniques to match patients by age, sex, body mass index (BMI), and other medical factors, making the comparison as fair as possible.
The primary goal was to measure weight change over a period of about one year. Secondary measures included the percentage of people who achieved at least 5%, 10%, or 15% weight loss. Safety outcomes and treatment continuation rates were also tracked to understand how patients tolerated each medication.
Primary Findings and Statistical Significance
The JAMA publication reported that people who took tirzepatide experienced greater weight loss than those who took semaglutide during the study period. On average, tirzepatide users lost a higher percentage of their body weight, and more patients reached meaningful weight-loss milestones.
For example, a larger share of tirzepatide users achieved ≥15% weight loss, a level that is often associated with significant health improvements such as better blood sugar control and lower blood pressure. The study also found that patients on tirzepatide tended to lose weight more quickly and maintain that loss more effectively over time.
These findings were statistically significant, meaning that the differences between the two groups were unlikely to be due to chance. Even after adjusting for baseline factors and medication adherence, the results remained consistent. This gave strong evidence that tirzepatide may provide greater benefits than existing therapies for obesity, including semaglutide.
Importantly, the JAMA article emphasized that these results came from real-world data, not just clinical trial settings. That means the findings could better reflect what doctors and patients might expect in everyday care.
How This Evidence Advances Prior Understanding of Obesity Treatment
Before this study, most knowledge about tirzepatide came from company-sponsored clinical trials, which are carefully controlled environments. Those trials showed strong results but often excluded certain patient types—such as people with multiple health problems or those using other medications.
The JAMA publication added an important layer of real-world evidence. It showed that tirzepatide’s effects were not only reproducible outside clinical trials but also superior to other current medications. This suggests that the medication may have a broader impact on public health if used widely.
The study also helped clarify the mechanistic potential of dual hormone activation. By acting on both GLP-1 and GIP receptors, tirzepatide may produce greater appetite suppression and improved energy use compared to single-pathway drugs like semaglutide. This insight could guide the next generation of obesity treatments and help scientists design even better therapies.
Another major advancement from the JAMA publication is its implication for clinical practice. For healthcare providers, the findings reinforce that significant, sustained weight loss can be achieved safely in real-world patients with tirzepatide. For policymakers and payers, the study provides strong evidence to support coverage decisions and broader access for patients struggling with obesity.
Finally, the publication shifts the broader narrative about obesity treatment. It strengthens the view that obesity is not simply a matter of willpower or lifestyle but a chronic, biologically driven disease that can and should be treated with effective medication. With data from one of the world’s leading medical journals, this evidence helps move obesity care toward a new era of precision and compassion.
Magnitude of Weight Loss Reported in the JAMA Study
The recent JAMA publication on tirzepatide marked a major step in understanding how much weight loss people can achieve with this new medicine. The study compared tirzepatide to other treatments, including semaglutide and older therapies, in adults living with obesity or overweight. The findings showed that tirzepatide led to significantly greater weight loss than almost any medicine studied before, even among people who did not have diabetes.
Percent Weight Reduction and Absolute Kilograms Lost
The JAMA analysis, which used real-world health-record data and clinical trial information, found that people taking tirzepatide lost about 20 % of their body weight on average after one year of treatment. This means that someone who weighed 100 kilograms (about 220 pounds) at the start of treatment typically lost about 20 kilograms (≈ 44 pounds) over twelve months.
In comparison, people who received semaglutide—a once-weekly GLP-1 receptor agonist—lost about 13 % to 15 % of their body weight over a similar period. Those taking placebo or standard lifestyle therapy alone lost far less—usually between 2 % and 3 %. These differences were not only statistically significant but also clinically meaningful. Even a 5 % weight loss can improve blood pressure, blood sugar, and cholesterol levels, so the results seen with tirzepatide represent a major metabolic benefit.
Comparison With Semaglutide, Placebo, and Historical Trials
When comparing tirzepatide and semaglutide directly, the JAMA researchers adjusted for factors such as age, sex, and baseline body-mass index (BMI). After this adjustment, tirzepatide users still had about 1.5 times greater odds of reaching major weight-loss goals (for example, losing ≥ 10 % of body weight) compared with semaglutide users.
In earlier randomized trials—such as the SURMOUNT-1 study—tirzepatide at the highest tested dose (15 mg weekly) produced average weight losses of 21 % after 72 weeks, while semaglutide 2.4 mg weekly in its pivotal study produced around 15 % after 68 weeks. The JAMA real-world findings were consistent with these results, suggesting that similar levels of weight loss occur outside tightly controlled research settings.
Against placebo, tirzepatide’s effect was striking. Placebo participants, who received lifestyle advice and behavioral counseling, lost roughly 2 %–3 % of body weight—typical of lifestyle interventions alone—while those on tirzepatide achieved up to 10 times that amount.
Duration and Trajectory of Weight Change
The JAMA data also described how weight loss unfolded over time. Most patients experienced steady and continuous loss for the first 6 to 9 months, after which the rate slowed and then reached a plateau. This pattern is typical of effective obesity medications: early rapid loss followed by maintenance.
In month-by-month analyses, people on tirzepatide had already lost about 5 % of their body weight by week 12, 10 % by week 24, and 15–20 % by one year, depending on their dose. The curve of weight change was both deeper and longer-lasting than that seen with semaglutide or older agents such as liraglutide.
An important note from the JAMA analysis was that adherence mattered. Participants who remained on tirzepatide consistently for 9–12 months achieved the greatest benefits, while those who stopped early regained weight more quickly. This underscores obesity’s chronic nature and the need for ongoing therapy.
Clinically Meaningful Thresholds of Weight Loss
Clinicians often classify weight-loss success by the proportion of patients reaching specific thresholds:
- ≥ 5 % loss – Improves blood pressure, glucose, and triglycerides
- ≥ 10 % loss – Often leads to remission of prediabetes and improved sleep apnea
- ≥ 15 % to 20 % loss – Associated with resolution of fatty liver and reduced cardiovascular risk
In the JAMA tirzepatide cohort, roughly 82 % of participants achieved ≥ 5 % loss, 63 % achieved ≥ 10 %, and 40 % reached ≥ 15 % loss after about one year. For semaglutide, these numbers were about 70 %, 49 %, and 27 %, respectively. For placebo or lifestyle-only groups, fewer than 20 % of people reached even the 5 % threshold.
These percentages translate into real health outcomes. Studies show that weight loss of 10–15 % can normalize liver enzymes in non-alcoholic fatty-liver disease, lower A1C levels, and even reduce the need for some blood-pressure medications. The JAMA data therefore point to clinically powerful effects extending well beyond the scale.
The JAMA publication demonstrated that tirzepatide produces unprecedented levels of weight loss in adults with obesity, with consistent results across controlled trials and real-world evidence. Average losses approached 20 % of body weight—substantially greater than other approved medications. The benefits appeared early, deepened over the first year, and were achieved by the majority of participants who stayed on treatment. These findings redefine what physicians and patients can expect from medical management of obesity and set a new benchmark for efficacy in this field.
Long-Term Efficacy and Weight Maintenance Outcomes
One of the most important findings from the JAMA publications on tirzepatide is that its weight loss effect is not only large—it can also be long-lasting when treatment is continued. In earlier studies, such as the SURMOUNT-1 trial, adults with obesity who received tirzepatide lost an average of 15% to 22% of their body weight over 72 weeks. However, questions remained about what would happen after that period. Could people keep the weight off if they continued using tirzepatide, or would they regain weight once the drug was stopped?
The JAMA article summarizing results from the SURMOUNT-4 trial gave important answers. In this follow-up study, participants first took tirzepatide for 36 weeks, losing about one-fifth of their starting body weight. They were then randomly assigned to either continue tirzepatide or switch to placebo for another 52 weeks. The results showed a clear difference: those who stayed on tirzepatide continued to lose small amounts of weight or maintained their loss, while those switched to placebo regained much of what they had lost.
This demonstrated that ongoing treatment with tirzepatide helps sustain weight loss over the long term. The results were consistent across different doses (10 mg and 15 mg), and benefits were similar in men and women, in people with or without diabetes, and across a wide range of body mass indexes (BMIs).
Weight Regain After Discontinuation and Chronic Therapy Implications
One of the most striking findings was how quickly weight was regained once tirzepatide was stopped. People who switched to placebo regained about half their lost weight within a year. This pattern is similar to what has been seen with other anti-obesity medications and even after certain types of bariatric surgery if long-term follow-up care is not maintained.
This pattern suggests that obesity is a chronic, relapsing condition that requires ongoing treatment—much like high blood pressure or diabetes. When medication is withdrawn, the body’s hormonal and metabolic systems can revert toward their previous state, increasing hunger and reducing energy use. Tirzepatide’s mechanism—mimicking the hormones GIP and GLP-1—acts on these systems to reduce appetite and improve satiety. Once the medication is removed, these signals diminish, and old patterns of eating and metabolism can return.
For clinicians, this means that obesity treatment with tirzepatide may need to be viewed as long-term or even indefinite therapy, depending on the individual’s goals and tolerance. Continuing therapy seems necessary for most people to preserve their weight reduction and associated health benefits, such as lower blood sugar and improved cardiovascular risk factors.
Mechanistic Explanation for Maintenance or Regain
The physiological reasons behind this pattern are well-understood. When people lose weight, their body responds as if it is in a state of energy shortage. Levels of hormones like leptin decrease, while ghrelin (the “hunger hormone”) increases. Metabolism also slows down, making it easier to regain weight. Tirzepatide counteracts these changes by acting on receptors in the brain and gut to suppress appetite and increase feelings of fullness after eating.
When treatment continues, these appetite-regulating effects remain active, helping the person eat less and maintain their new lower weight. When tirzepatide is stopped, the body’s defense mechanisms against weight loss are no longer suppressed, and hunger tends to return to pre-treatment levels or even higher. This biological rebound helps explain why stopping medication often leads to partial or complete weight regain.
Importantly, the JAMA studies suggest that ongoing tirzepatide therapy maintains not only weight reduction but also metabolic improvements—such as better glucose control and lower triglycerides—indicating that long-term therapy provides continuing systemic benefits.
Clinical Interpretation of Sustained Efficacy
From a clinical standpoint, these findings redefine how obesity may be managed. In the past, weight loss treatments were often short-term interventions. The JAMA evidence supports a chronic care model, in which tirzepatide functions similarly to medications for hypertension or diabetes—maintained for as long as benefits outweigh risks.
Clinicians should therefore counsel patients that tirzepatide is not a temporary “diet pill.” Instead, it is a metabolic therapy that works as long as it is taken. Patients who stop may regain weight, not because of personal failure, but due to predictable biological mechanisms.
These insights also affect health systems and payers. If long-term use is needed to sustain benefits, ongoing access and insurance coverage become critical. For patients, the findings may help reduce guilt or stigma around weight regain after stopping medication. Instead, the data reinforce the concept that obesity is a treatable but chronic condition requiring sustained care.
The JAMA publication and related SURMOUNT-4 data show that tirzepatide produces powerful and durable weight loss—up to 20% of body weight—and that continued treatment is essential to maintain these effects. Discontinuation leads to partial weight regain, emphasizing the chronic nature of obesity. These findings shift clinical thinking toward continuous management rather than short-term intervention, marking a major step forward in the long-term treatment of obesity.
Safety Profile and Adverse Effects
Understanding the safety of tirzepatide is just as important as understanding how much weight it helps people lose. The JAMA publications and other clinical trials have provided detailed information on what side effects can occur, how common they are, and how serious they tend to be. In general, tirzepatide has a safety profile that is similar to other incretin-based drugs, such as GLP-1 receptor agonists, but with a few points worth special attention.
Common Side Effects
The most frequent side effects reported in the JAMA study and in earlier SURMOUNT trials were related to the digestive system. These included nausea, diarrhea, vomiting, and constipation. Most people described these symptoms as mild to moderate. They usually appeared soon after starting treatment or after a dose increase.
In the JAMA findings, roughly 20 % – 25 % of participants reported nausea, and about 10 % – 15 % reported diarrhea. Vomiting and constipation were less frequent but still present in a smaller number of people. These side effects were more likely when the dose was increased quickly, suggesting that the body needs time to adjust to the medicine.
Healthcare providers are advised to use a gradual dose-titration schedule—starting low and increasing slowly—to reduce discomfort. Most patients found that their symptoms improved within several weeks as their digestive system adapted. Eating smaller meals and avoiding high-fat or spicy foods also helped.
Serious or Severe Adverse Events
Severe side effects were uncommon. In the JAMA observational analysis, only a small percentage of participants stopped tirzepatide because of side effects. The discontinuation rate was similar to what has been seen with other drugs in the same class, such as semaglutide.
No new safety concerns appeared that had not already been described in earlier tirzepatide trials. There were no major increases in pancreatitis, gallbladder problems, or thyroid tumors compared with other incretin-based treatments, though these remain topics of ongoing monitoring. A few patients experienced low blood sugar (hypoglycemia), but this mainly occurred in people who also had type 2 diabetes and were taking other glucose-lowering medicines like insulin or sulfonylureas.
Comparison With Other Incretin-Based Therapies
When comparing tirzepatide with other GLP-1 receptor agonists, such as semaglutide or liraglutide, the side-effect patterns are similar. Nausea and vomiting occur at about the same rate, and gastrointestinal upset remains the main limitation to tolerability. However, tirzepatide’s dual action on GIP and GLP-1 receptors does not appear to increase overall risk.
Interestingly, some analyses suggest that tirzepatide might even cause slightly fewer gastrointestinal symptoms at equivalent weight-loss levels, possibly because the GIP component modulates the gut response. That said, not all studies agree, and individual experience can vary.
Safety in Special Populations
The JAMA publication focused mainly on adults with obesity, including those with and without diabetes. In both groups, safety findings were consistent. No increased risk of cardiovascular events or kidney problems was reported in the time frame studied.
For older adults, those over 65, tirzepatide appeared to have similar tolerability, though caution is always advised because older patients may be more sensitive to dehydration or gastrointestinal distress. For women of child-bearing potential, tirzepatide is not recommended during pregnancy or breastfeeding, following standard guidance for this drug class.
Long-Term Safety Considerations
Because tirzepatide is relatively new, researchers continue to collect long-term safety data. The JAMA studies covered periods of up to about one year, while extension trials like SURMOUNT-4 followed some patients longer. Thus far, no unexpected patterns have appeared, but long-term outcomes—such as sustained effects on heart health, gallbladder function, and thyroid markers—are still being studied.
Animal studies had shown a risk of certain thyroid tumors at very high doses, which is why tirzepatide, like other GLP-1 receptor agonists, carries a warning about medullary thyroid carcinoma and should not be used in people with a personal or family history of that condition. However, human studies to date have not shown an increased risk.
Managing and Monitoring Side Effects
Good patient education plays an important role in managing tirzepatide safely. Clinicians often recommend:
- Starting at the lowest available dose and increasing every four weeks only if tolerated.
- Drinking enough fluids to prevent dehydration from vomiting or diarrhea.
- Eating slowly, avoiding overeating, and monitoring for signs of hypoglycemia if on other diabetes medications.
- Reporting persistent abdominal pain or signs of gallbladder problems.
Most side effects can be managed with supportive care and temporary dose adjustments. If nausea or vomiting become severe or do not improve, the medication may be paused or discontinued.
The JAMA publication confirmed that tirzepatide’s safety profile is consistent with known data from previous clinical trials. Most side effects involve the digestive system and are mild to moderate. Serious events are uncommon, and the overall tolerability is acceptable when the drug is introduced gradually and monitored properly.
This balance of strong weight-loss benefits and a manageable safety profile supports tirzepatide’s role as a major new option for treating obesity. Continuous follow-up studies and real-world monitoring will remain essential to confirm long-term safety as its use expands across larger and more diverse patient populations.
Study Population and Applicability
The JAMA publication on tirzepatide included adults who were living with obesity or who were overweight with related health conditions. In most studies, obesity was defined as a body mass index (BMI) of 30 kg/m² or higher, and overweight as a BMI of 27 kg/m² or higher when combined with another weight-related condition, such as high blood pressure, abnormal cholesterol, or prediabetes. Participants were generally adults between 18 and 75 years old.
The main goal was to study people who represented those most likely to benefit from medical weight-loss treatment. Individuals who had type 2 diabetes were sometimes excluded in obesity-only trials, because diabetes can change how the drug affects weight. Other exclusions included people who had undergone bariatric (weight-loss) surgery, those using other weight-loss medicines, and anyone with serious gastrointestinal diseases or a history of pancreatitis. Pregnant or breastfeeding individuals were also excluded because tirzepatide’s effects during pregnancy are not yet known.
By defining these criteria, researchers created a group that could safely receive tirzepatide and that clearly showed the medication’s direct effect on weight, without major outside factors influencing the results.
Patient Demographics and Comorbidity Patterns
The JAMA analysis represented a large and diverse population. However, as with many clinical studies, most participants were middle-aged adults, often in their 40s to 60s. A typical baseline weight was around 100–110 kilograms (220–240 pounds), with average BMI values in the mid-30s kg/m² range.
Men and women were both included, though many of the participants were women, which reflects obesity’s higher prevalence in women across many regions. The majority of study participants were non-Hispanic White, but there were also people of other racial and ethnic groups. The degree of diversity depended on the data source—some JAMA studies used electronic health records (EHR) from large U.S. systems that included multi-ethnic populations, while others used international clinical trial data.
Common comorbidities among participants included hypertension, dyslipidemia (abnormal cholesterol levels), and prediabetes. These conditions are often part of what doctors call metabolic syndrome, a cluster of risk factors for heart disease and diabetes. Some participants had obstructive sleep apnea, joint problems, or non-alcoholic fatty liver disease (NAFLD), which are also linked to obesity.
The presence of these comorbidities was important because it allowed researchers to see whether tirzepatide helped improve more than just weight. In many cases, people taking tirzepatide also experienced better blood sugar control, lower triglycerides, and improved blood pressure, even if the study was not designed to test those outcomes directly.
Subgroup Outcomes (e.g., BMI Category, Sex, Diabetes Status)
The JAMA publication and related trials often analyzed how tirzepatide worked across different subgroups of people. This helps doctors know whether the treatment benefits are consistent or if they vary by certain characteristics.
By BMI Category: Participants with a higher BMI (for example, ≥ 35 kg/m²) tended to lose a greater absolute amount of weight, but when measured as a percentage of body weight, results were similar across BMI groups. This means tirzepatide was effective for both moderate and severe obesity.
By Sex: Both men and women achieved meaningful weight reduction. Some analyses showed women might have slightly higher percentage loss, but these differences were small and likely related to body-composition differences rather than drug performance.
By Diabetes Status: People without diabetes generally lost more weight than those with type 2 diabetes. This may be because individuals with diabetes often have different hormonal balances and may require lower doses. Still, both groups achieved clinically significant weight reduction compared with controls.
By Age: Older adults (above 65 years) also benefited, though sometimes with slower progress due to differences in metabolism and lower starting doses. Importantly, there were no unique safety concerns observed in older participants.
Subgroup analyses like these show that tirzepatide’s effects are broad and reliable, though outcomes can vary slightly depending on personal health factors.
Generalizability to Broader Clinical Populations
When researchers talk about applicability or generalizability, they mean whether the results seen in the study can be expected in the real world. The JAMA findings are encouraging because they align closely with what has been seen in other real-world data sources and clinical trials.
However, there are still some limits to generalizability. First, most participants were already engaged with health care systems and able to follow a structured medical plan. In real-life settings, not everyone has the same level of access to medical care or insurance coverage. Second, the studies typically involved regular follow-up visits and guidance on diet and lifestyle, which may be harder to maintain outside of a trial.
Another consideration is ethnic and socioeconomic diversity. While the study populations were more diverse than in older obesity trials, under-representation of certain groups—such as Hispanic, Black, or Asian populations—still exists. Because of this, ongoing research is examining how cultural, dietary, and genetic differences might affect response to tirzepatide.
Finally, the trials generally excluded people with serious psychiatric disorders, advanced heart failure, or uncontrolled endocrine diseases. Clinicians must therefore be cautious when applying these results to such patients until more evidence becomes available.
The JAMA publication on tirzepatide studied a population that represents many—but not all—people with obesity. Participants were adults with moderate to severe obesity, often with common metabolic health issues, but without severe chronic illness or active diabetes in most obesity-specific trials. The findings showed consistent and significant weight loss across age, sex, and BMI groups, with manageable side effects.
While the study population gives strong confidence in tirzepatide’s benefits, ongoing research should expand on these results by including broader, more varied patient groups. This will help confirm how tirzepatide performs across the full spectrum of individuals living with obesity in the real world.
Comparison with Other Tirzepatide Trials and Evidence
The JAMA publication on tirzepatide adds a new layer of evidence to what was already known from earlier phase III clinical trials, such as the SURMOUNT and SURPASS studies. Understanding how the JAMA data relate to these earlier findings helps clinicians and researchers see whether tirzepatide performs as well in the real world as it does under controlled trial conditions.
Alignment with Pivotal SURMOUNT and SURPASS Programs
Before the JAMA paper, most information about tirzepatide came from the SURMOUNT and SURPASS trials. These were large, well-controlled studies that included thousands of participants with obesity, with or without type 2 diabetes.
In SURMOUNT-1, adults with obesity but no diabetes took tirzepatide for 72 weeks. Depending on the dose (5 mg, 10 mg, 15 mg), they lost about 15 % to 22 % of their body weight on average. That level of weight loss is close to what is typically achieved with some types of bariatric surgery, which was a major finding at the time.
SURMOUNT-2 focused on participants who had type 2 diabetes and obesity. Weight loss in that group was smaller—around 12 % to 14 % on the higher doses—but still much greater than what had been seen with older GLP-1 drugs.
The SURPASS program mainly examined tirzepatide as a treatment for diabetes, but it also showed that the drug led to large reductions in both blood glucose and body weight. These early results demonstrated tirzepatide’s potential not only for diabetes management but also for obesity treatment more broadly.
The JAMA article’s results generally align with these controlled trials. Patients in the JAMA study who were prescribed tirzepatide in real-world settings experienced similar or even greater weight loss compared with those on semaglutide, another leading GLP-1 receptor agonist. This consistency reinforces the credibility of tirzepatide’s strong clinical effects.
Differences in Methodology or Endpoints
While the SURMOUNT and SURPASS trials were randomized controlled trials (RCTs), the JAMA publication used real-world data, often drawn from electronic health records (EHRs) or medical databases. That means patients were not randomly assigned to treatment, and doctors prescribed tirzepatide or semaglutide according to usual practice.
Because of this design difference, the JAMA study provides insights into how tirzepatide works in daily life, outside of a research setting. Real-world evidence helps answer questions that clinical trials cannot fully address—such as how people with many different health conditions respond to the drug, how adherence affects outcomes, and what happens when patients are treated by various types of providers.
Endpoints also differed. The SURMOUNT trials measured exact changes in body weight under close supervision, with controlled diet and lifestyle guidance. The JAMA study relied on weight data recorded during clinic visits, which can vary in accuracy and frequency. Even so, the weight changes observed in JAMA were consistent enough to show a clear trend favoring tirzepatide.
Real-World Versus Clinical Trial Performance
In randomized trials, participants are carefully selected and monitored, which can sometimes make results look better than what occurs in typical practice. However, in the JAMA report, tirzepatide’s real-world results were not only similar but often slightly better than those seen in clinical trials when compared to semaglutide users.
There are a few possible reasons for this. Many real-world patients are motivated to lose weight and may combine medication with lifestyle changes. In addition, tirzepatide’s dual action on GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) receptors may produce stronger appetite suppression and metabolic effects than GLP-1-only drugs. The JAMA data confirm that these effects translate well into everyday clinical outcomes.
However, real-world studies have their own challenges. Medication adherence, dosage titration, and insurance coverage vary widely, which can influence outcomes. Still, the fact that tirzepatide showed robust results across diverse populations strengthens confidence in its practical effectiveness.
What the JAMA Data Uniquely Contribute
The unique contribution of the JAMA publication lies in its demonstration of real-world effectiveness and its comparison to an active, widely used medication—semaglutide. Most earlier trials compared tirzepatide to placebo or to other diabetes medications. By contrast, the JAMA study directly evaluated two advanced incretin-based therapies head-to-head in large patient populations.
This head-to-head analysis gives healthcare professionals a clearer understanding of relative efficacy outside of controlled trials. It also provides valuable data for policymakers and insurers who must decide on coverage and cost-effectiveness.
Another important contribution is the diversity of the study population. Because EHR data include patients from different age groups, ethnic backgrounds, and clinical settings, the JAMA publication helps show that tirzepatide’s benefits are not limited to narrowly selected trial participants.
While SURMOUNT and SURPASS established tirzepatide as a powerful medication for weight and glucose reduction, the JAMA study confirms that these benefits hold true in routine practice. It closes the gap between research and reality, showing that tirzepatide performs strongly not just under ideal trial conditions but also in the hands of everyday patients and clinicians. This strengthens its role as a transformative agent in the treatment of obesity.
Mechanistic Insights: Why Tirzepatide Performs Differently
Tirzepatide works in a new and interesting way. It acts on two important hormone receptors in the body — GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1). These hormones belong to a group called incretins, which are released by the gut after eating. They help regulate blood sugar and appetite.
Older medicines for obesity, like semaglutide, act only on the GLP-1 receptor. Tirzepatide, however, activates both GIP and GLP-1 receptors. Scientists call it a dual incretin receptor agonist or “twincretin.”
The GIP receptor plays a role in insulin release and fat metabolism, while the GLP-1 receptor affects appetite, stomach emptying, and satiety signals in the brain. By targeting both, tirzepatide may produce additive or even synergistic effects — meaning that the combined action is greater than the effect of either hormone alone.
In simple terms, tirzepatide helps the body respond more efficiently to food by improving how insulin works, reducing hunger, and lowering energy intake. This dual mechanism may explain why the JAMA studies show larger and more consistent weight loss compared with single-hormone drugs.
Pharmacodynamics and Dose-Response Relationships
Tirzepatide’s clinical effect depends strongly on dose and duration. In trials, patients started at a low dose (2.5 mg weekly) to reduce side effects, and the dose was slowly increased to 10 mg or 15 mg once weekly. Higher doses were linked to greater average weight loss, showing a clear dose–response relationship.
This pattern supports that the drug’s biological effects build gradually. As tirzepatide levels stabilize, appetite decreases and food intake declines. The GLP-1 effect mainly reduces hunger and slows digestion, while the GIP effect improves fat metabolism and enhances insulin sensitivity.
The medication’s long half-life — about five days — allows for once-weekly injections. This is convenient for patients and helps maintain steady hormone levels in the blood. A stable pharmacologic profile reduces peaks and troughs that could lead to side effects or reduced benefit.
In the JAMA data, this steady weekly rhythm translated to sustained calorie reduction and gradual fat mass loss, without significant muscle loss. Over time, these small weekly effects add up to meaningful and durable changes in body weight.
Physiologic Rationale for Enhanced Satiety and Energy Regulation
Tirzepatide influences multiple organ systems that control hunger, digestion, and energy balance.
- In the brain, particularly in the hypothalamus, it increases signals that tell the body it is full and decreases signals that promote food-seeking behavior. This leads to a natural reduction in calorie intake.
- In the stomach, tirzepatide slows down gastric emptying — meaning food stays in the stomach longer. This prolongs the feeling of fullness after meals.
- In the pancreas, it stimulates insulin release only when blood sugar levels rise, which helps maintain normal glucose without causing hypoglycemia.
- In fat tissue, GIP receptor activity may shift energy storage and promote fat burning rather than fat accumulation.
Together, these effects create a “metabolic reset,” where the body learns to use energy more efficiently and store less excess fat. Patients tend to eat less without feeling deprived, and their metabolism adjusts in a way that supports steady, healthy weight reduction.
What makes tirzepatide stand out is that it acts both centrally (in the brain) and peripherally (in the gut and fat tissue). This multi-level approach appears to correct several mechanisms that drive chronic weight gain, not just one.
Translating Mechanism into Clinical Outcomes
The JAMA findings — showing larger and more sustained weight loss compared with other treatments — are consistent with these biological mechanisms.
Because tirzepatide acts on two incretin pathways, it may:
- Reduce appetite more effectively than GLP-1–only drugs.
- Lower food cravings, especially for high-fat and high-carbohydrate foods.
- Improve insulin sensitivity, which helps control blood sugar in patients with or without diabetes.
- Enhance fat metabolism, leading to a higher proportion of fat loss rather than lean tissue loss.
In addition, tirzepatide’s dual action may produce better cardiovascular and metabolic outcomes, though more long-term studies are needed to confirm this. Early evidence suggests benefits in blood pressure, lipid levels, and liver fat reduction — all key risk factors in obesity-related diseases.
This broader metabolic effect is important because obesity is not only about excess weight; it involves hormonal resistance, inflammation, and metabolic dysfunction. By acting on several of these pathways, tirzepatide appears to shift the body toward a healthier metabolic state, supporting durable weight control.
Clinically, this means that patients on tirzepatide are not just “losing weight” — they are experiencing a full-body metabolic improvement. The dual hormone activation model may represent the next generation of obesity treatment, combining hormonal balance, energy regulation, and appetite control in one therapy.
Tirzepatide’s unique dual mechanism explains why its results in the JAMA publications are so compelling. It works by stimulating both GIP and GLP-1 receptors, leading to greater metabolic efficiency, reduced appetite, improved glucose control, and enhanced fat utilization. This integrated approach marks a new phase in obesity pharmacology — one where the body’s natural hormone systems are guided to restore balance, rather than simply suppress appetite or block absorption.
Implications for Clinical Practice and Health Systems
The JAMA publication on tirzepatide marks an important moment in how doctors and healthcare systems think about obesity treatment. Until recently, obesity was often viewed mainly as a lifestyle issue—something to be managed through diet and exercise alone. The data published in JAMA provide strong scientific evidence that obesity is a chronic, treatable disease that responds to targeted medical therapy. Tirzepatide’s performance in real-world and clinical studies suggests that health systems, clinicians, and policymakers may need to adjust how they approach obesity management—from the clinic level to national health policies.
Integration into Obesity Management Guidelines
The first impact of the JAMA findings is on clinical guidelines. Most medical societies, such as the American Diabetes Association (ADA) and the Obesity Society, already recommend medications for people with obesity when lifestyle changes alone are not enough. However, tirzepatide’s results—showing average weight loss exceeding 15% in many participants—are reshaping how these recommendations are prioritized.
In practice, tirzepatide may move from being a “last resort” drug to one considered earlier in treatment. The data show that early pharmacologic intervention may help prevent obesity-related complications such as type 2 diabetes, hypertension, fatty liver disease, and cardiovascular risk. As a result, guideline committees may update their frameworks to position incretin-based therapies like tirzepatide as first-line options for eligible patients, especially those with severe obesity or multiple comorbidities.
Clinical teams will also need to adapt. Physicians, nurse practitioners, and pharmacists must learn dosing protocols, recognize early side effects, and know how to monitor treatment progress safely. The JAMA findings support a shift from short-term weight programs to chronic disease management models—similar to those used for diabetes or hypertension.
Prescriber Perspectives and Adoption Trends
For many clinicians, the JAMA publication provides confidence in using tirzepatide outside of diabetes care. The evidence supports its use in patients with obesity alone, confirming efficacy and safety across diverse populations. Prescribers are likely to become more comfortable recommending it, especially after seeing both clinical trial and real-world data align.
However, adoption depends on more than clinical results. Doctors must consider individualized care—factors such as age, comorbidities, cost, and patient preference. Many clinicians will start tirzepatide at lower doses and titrate slowly to improve tolerance. Education programs for healthcare professionals will be key, ensuring consistent and safe prescribing patterns.
Primary care providers—who often see obesity as part of broader metabolic disease—are expected to play a growing role. The JAMA findings make it clear that obesity treatment should not remain siloed in specialty care. Integrating pharmacotherapy into everyday primary care practice could make treatment more accessible and reduce the burden of advanced obesity complications later.
Access, Equity, and Insurance Coverage Considerations
While tirzepatide’s results are promising, its real-world impact depends on access. In the United States and many other countries, weight-loss medications are not consistently covered by insurance or public health systems. The JAMA publication may help change this by providing strong evidence of clinical benefit, similar to what triggered coverage changes for diabetes drugs in the past.
Still, barriers remain. Tirzepatide is expensive, and cost is one of the main reasons patients discontinue therapy. Many insurers classify obesity drugs as “lifestyle treatments,” not essential medications, limiting reimbursement. The JAMA data—showing significant reductions in body weight and associated risk factors—may persuade payers that covering these drugs prevents long-term healthcare costs, such as hospitalizations for heart disease or diabetes complications.
Equity is another issue. Studies show that people in lower-income or minority populations often have less access to advanced obesity treatments. To ensure fairness, health systems will need to address disparities in prescribing, affordability, and follow-up care. Outreach programs, patient education, and community-based obesity clinics could help bridge these gaps.
Cost-Effectiveness and Public Health Relevance
From a health economics perspective, the JAMA findings raise important questions. Weight loss achieved with tirzepatide can reduce the risk of major chronic diseases. Modeling studies suggest that if sustained, this could lower long-term healthcare costs. Reduced incidence of type 2 diabetes, cardiovascular disease, and fatty liver disease translates to fewer hospitalizations and better quality of life.
However, the cost-effectiveness of tirzepatide depends on treatment duration and price. Because obesity is a chronic condition, patients may need lifelong therapy to maintain benefits. Policymakers will need to evaluate how to make such therapies sustainable—through negotiated pricing, insurance coverage, or national subsidy programs.
At the public health level, the implications are significant. Obesity rates continue to rise worldwide, and traditional interventions alone have not reversed the trend. If widely implemented, medications like tirzepatide could shift the trajectory by helping millions achieve meaningful and lasting weight reduction. Public health agencies may also use these findings to strengthen campaigns that treat obesity as a medical disease rather than a personal failure, reducing stigma and encouraging medical consultation.
The JAMA publication on tirzepatide is more than just a new research finding—it represents a major turning point in how health systems approach obesity. It encourages a model that combines medical therapy, lifestyle support, and ongoing monitoring, similar to chronic disease care frameworks.
For clinicians, it provides reassurance that pharmacologic therapy is not only effective but necessary for many patients. For health systems and insurers, it builds the case for broader coverage and investment in obesity care. And for public health leaders, it reinforces that addressing obesity through evidence-based medicine can lead to large-scale benefits in population health and economic sustainability.
The JAMA findings push the medical community closer to recognizing obesity as a chronic, manageable condition—one that deserves the same attention, funding, and long-term planning as any other major health challenge.
Limitations and Areas for Future Research
The JAMA publication on tirzepatide offers strong evidence that this medication can produce major and sustained weight loss in people with obesity. However, even large and well-designed studies have limits. Understanding these limitations helps doctors, patients, and researchers interpret the findings correctly and plan better studies in the future. This section reviews key limitations of the current evidence and highlights where more research is still needed.
Observational or Registry-Based Limitations in JAMA Studies
Many JAMA articles on tirzepatide use electronic health record (EHR) data or observational registries rather than traditional randomized controlled trials (RCTs). While these real-world data are valuable, they come with challenges.
Unlike RCTs, observational studies do not randomly assign participants to receive tirzepatide or another treatment. Instead, researchers analyze data from people who were already prescribed the medication in clinical practice. This means that selection bias can occur—patients who get tirzepatide may differ from those who don’t in important ways, such as health status, motivation, or access to care. These differences can influence weight loss outcomes even before treatment begins.
Another issue is confounding, where other factors (like exercise, diet changes, or use of other medications) affect results. Researchers often use statistical methods to adjust for these variables, but such adjustments can’t eliminate all bias. In addition, EHR data rely on accurate record-keeping. Missing, incomplete, or inconsistent data entries can reduce accuracy. For example, body weight may not always be measured using the same methods or at regular intervals, and side effects may go unreported if not coded properly.
Finally, observational data often lack the strict monitoring that occurs in clinical trials. Without standardized follow-up, differences in how doctors manage their patients can lead to variable results. Thus, while JAMA’s real-world analyses support tirzepatide’s strong effects, they should be viewed as complementary—not a replacement—for randomized studies.
Data Gaps: Duration, Adherence, and Discontinuation Outcomes
Another key limitation involves the length of follow-up and adherence to therapy. Most published studies, including those in JAMA, report outcomes up to one year, sometimes a bit longer. Obesity, however, is a chronic condition that requires long-term management. We do not yet know what happens over several years of continuous tirzepatide use, or what percentage of patients can maintain weight loss over that time.
Adherence is also an important concern. In clinical trials, adherence is closely tracked. In real-world practice, patients often stop or miss doses because of side effects, cost, or injection fatigue. This may lead to less effective results than those seen in research settings. Few large-scale studies have examined how adherence affects long-term outcomes outside of trials.
Discontinuation—when people stop taking the medication—also raises questions. Early data show that weight regain often begins soon after stopping tirzepatide. This suggests that ongoing therapy may be necessary to maintain benefits. However, the long-term safety and practicality of indefinite use are not yet clear. More research is needed to determine the optimal treatment duration, maintenance dosing, and potential strategies for tapering or combining therapy with lifestyle or behavioral programs.
Population Bias and Real-World Constraints
The populations included in JAMA analyses may not fully reflect everyone who could benefit from tirzepatide. For example, participants in these studies often come from health systems with better access to medications and follow-up care. People from lower-income backgrounds or with limited healthcare access may be underrepresented. This introduces population bias and limits generalizability.
In addition, most studies exclude people with certain health conditions, such as severe kidney or liver disease, unstable heart disease, or eating disorders. Therefore, we cannot assume tirzepatide’s safety or effectiveness in these groups without further study. Similarly, data are limited in older adults, adolescents, and certain racial or ethnic populations.
Real-world constraints such as insurance coverage, cost, and drug availability also affect who actually receives tirzepatide. These social and economic barriers mean that the population studied in JAMA may not represent the broader group of individuals struggling with obesity worldwide. Understanding how these barriers shape treatment outcomes is an important next step.
Emerging Questions for Ongoing and Future Trials
Despite its strong results, the JAMA publication leaves several key scientific and clinical questions unanswered.
First, researchers need to determine how long tirzepatide can be safely used and whether there are any long-term effects that appear after several years. Questions about heart health, kidney function, and bone metabolism during extended use remain open.
Second, future studies should explore how tirzepatide works in combination with other obesity interventions—such as behavioral counseling, digital health tools, or bariatric surgery. Understanding combination strategies could help optimize results while minimizing side effects.
Third, it is important to study individual variation in response. Some patients experience dramatic weight loss, while others lose much less despite similar doses. Genetic factors, hormonal differences, and lifestyle habits may explain this variation. Personalized approaches could help predict who benefits most from treatment.
Finally, researchers should continue to explore mechanisms of weight regain and how to prevent it. This includes studying metabolic adaptations, appetite regulation, and changes in gut hormones after stopping therapy.
Future JAMA studies, and similar peer-reviewed work, will need to use diverse populations, longer follow-ups, and randomized designs to address these issues. Doing so will strengthen confidence in tirzepatide’s role as a long-term, safe, and equitable treatment for obesity.
While the JAMA findings on tirzepatide mark a turning point in obesity treatment, they are not the final word. Observational design, limited follow-up, uneven population representation, and open research questions remind us that science evolves through ongoing study. Continued investigation—especially into long-term safety, adherence, and equitable access—will be essential to fully understand tirzepatide’s place in managing obesity.
Conclusion
The JAMA publication on tirzepatide marks a turning point in how obesity is understood and treated in modern medicine. For decades, obesity has been viewed mainly as a condition of willpower or lifestyle, but studies like this one have reframed it as a chronic, biological disease that can respond to targeted therapy. The research in JAMA adds strong scientific support for the idea that obesity treatment should be approached like other long-term diseases—through ongoing, evidence-based medical care rather than short-term solutions.
The findings highlight tirzepatide as one of the most effective medications currently available for weight loss. The study showed that people treated with tirzepatide achieved substantial and clinically meaningful reductions in body weight, often surpassing those seen with earlier medications such as semaglutide. These changes were not small or symbolic—they represented double-digit percentages of total body weight, which can translate into major improvements in blood pressure, glucose control, cholesterol levels, and overall metabolic health. Such outcomes are particularly important because even modest weight loss can lower the risk of heart disease, type 2 diabetes, and other complications related to excess weight.
The publication also emphasized the sustainability of results with continued use. Patients who stayed on tirzepatide maintained their weight loss, while those who discontinued therapy tended to regain some of the lost weight. This finding reinforces a new understanding of obesity as a chronic condition that requires long-term management rather than temporary treatment. Just as patients with high blood pressure or diabetes often need ongoing therapy to maintain control, individuals with obesity may require continuous medication support to prevent weight regain and maintain metabolic stability. This concept may shift how healthcare systems view treatment success—from short-term goals to lifelong disease management.
Safety findings were also meaningful. While gastrointestinal side effects such as nausea, diarrhea, or vomiting were relatively common, most were mild or moderate and tended to lessen with time or dose adjustment. The JAMA data confirmed what earlier clinical trials had shown: that the benefits of tirzepatide generally outweigh the risks for most people when used appropriately. Importantly, serious adverse events were rare, and treatment discontinuation due to side effects was relatively low. This supports tirzepatide’s potential as a well-tolerated and sustainable therapy for long-term use.
Beyond individual outcomes, the JAMA research has wider implications for clinical practice and healthcare systems. The results are likely to influence obesity management guidelines, encouraging clinicians to view pharmacotherapy as a central, not peripheral, part of treatment. Until recently, lifestyle modification—diet and exercise—was seen as the cornerstone of obesity management. While those elements remain critical, the JAMA findings show that combining lifestyle approaches with medication can dramatically improve success rates. This integrated model of care could redefine obesity clinics, primary care practices, and endocrinology departments around the world.
However, this shift also raises important questions about accessibility. Tirzepatide is a relatively new drug, and its cost and insurance coverage vary widely. The JAMA study provides compelling evidence for its effectiveness, but if access remains limited, many patients will not be able to benefit. Policymakers and payers may need to reconsider how obesity is prioritized within healthcare budgets. Treating obesity effectively could reduce the long-term burden of diabetes, cardiovascular disease, and other conditions, leading to cost savings over time. In this way, the JAMA findings could have far-reaching economic as well as clinical consequences.
Another impact of this publication lies in how it will shape future research. The success of tirzepatide has sparked interest in next-generation incretin-based therapies that combine or modify GLP-1 and GIP receptor activity. Researchers are also studying how these drugs affect appetite regulation, energy balance, and even brain pathways linked to reward and craving. Long-term studies will be essential to determine whether benefits persist over years, whether there are additional metabolic or cardiovascular advantages, and how best to combine medications with behavioral or surgical interventions.
For clinicians, the message from the JAMA study is clear: obesity should be treated proactively, with the same seriousness and continuity as other chronic diseases. For patients, it offers hope that meaningful, lasting weight loss is achievable through safe and scientifically supported means. And for healthcare systems, it signals the beginning of a new era—one where evidence-based obesity treatment is a standard part of care, not an exception.
In conclusion, the JAMA publication on tirzepatide is more than just another research paper; it represents a paradigm shift. It provides powerful evidence that obesity treatment has entered a new stage—one defined by effective, biologically targeted therapy and long-term disease management. As clinicians, researchers, and policymakers digest these findings, the message is simple but transformative: treating obesity with the same rigor and compassion as other chronic diseases can change not only lives but the health of entire populations.
Research Citations
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Zhao, L., Cheng, Z., Lu, Y., et al. (2024). Tirzepatide for weight reduction in Chinese adults with obesity: The SURMOUNT-CN randomized clinical trial. JAMA, 332(7), 551–560. DOI: 10.1001/jama.2024.9217
Rosenstock, J., Frías, J. P., Rodbard, H. W., et al. (2023). Tirzepatide vs insulin lispro added to basal insulin in type 2 diabetes: The SURPASS-6 randomized clinical trial. JAMA, 330(17), 1631–1640. DOI: 10.1001/jama.2023.20294
Rodriguez, P. J., Goodwin Cartwright, B. M., Gratzl, S., et al. (2024). Semaglutide vs tirzepatide for weight loss in adults with overweight or obesity. JAMA Internal Medicine, 184(9), 1056–1064. DOI: 10.1001/jamainternmed.2024.2525
Chuang, M.-H., Chen, J.-Y., Wang, H.-Y., Jiang, Z.-H., & Wu, V.-C. (2024). Clinical outcomes of tirzepatide or GLP-1 receptor agonists in individuals with type 2 diabetes. JAMA Network Open, 7(8), e2427258. DOI: 10.1001/jamanetworkopen.2024.27258
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Questions and Answers: Tirzepatide JAMA
The article asks whether once-weekly subcutaneous tirzepatide in conjunction with diet and physical activity helps maintain body weight reduction in individuals after an initial weight loss phase.
It was a randomized clinical trial where participants who had achieved weight loss were randomized to continue tirzepatide versus placebo (with lifestyle intervention) to assess maintenance of weight loss.
The trial found that continued treatment with tirzepatide significantly improved maintenance of weight reduction compared to placebo, meaning fewer participants regained weight when kept on the drug.
That study reported that adding tirzepatide (various doses) to basal insulin resulted in significant reductions in mean glycated hemoglobin (HbA₁c) compared to insulin lispro, showing that tirzepatide can further improve glycemic control.
The JAMA-reported trial compared 5-mg, 10-mg, and 15-mg doses of once-weekly tirzepatide against placebo in participants on background lifestyle modifications.
In one JAMA summary article, patients in tirzepatide trials achieved weight losses up to about 21% of baseline body weight, compared with much smaller (around 3%) losses in placebo arms.
The trial noted that gastrointestinal adverse events such as nausea and diarrhea remained among the most common side effects, and rates of discontinuation increased with higher doses, but the continued use was generally tolerated in many participants.
Commentators noted uncertainty about how much exercise or calorie restriction is needed alongside tirzepatide, and whether long-term benefits persist after stopping the drug.
Yes — tirzepatide was associated with greater weight loss than semaglutide in clinical settings, with higher likelihoods of achieving 5%, 10%, and 15% weight reduction.
It suggests that for sustained weight control, ongoing administration of tirzepatide (rather than stopping after initial weight loss) may be necessary to prevent weight regain.
