Individualized virtual integrative medicine (IVIM): A clinical model for enhanced GLP-1 therapeutic outcomes

Abstract

Background

Here we show results of 1,131 patients on therapy with semaglutide who underwent a comprehensive clinical protocol utilizing the Individualized Virtual Integrative Medicine (IVIM) approach, evaluating the protocol as a comprehensive clinical care model for patients utilizing GLP-1 medications.

Methods

This is a retrospective analysis of patients who completed at least 365 days of the protocol while on GLP-1 therapy with semaglutide. Patients with a body-mass index (BMI) of 30 or greater were included. Patients were prescribed personalized therapy with semaglutide based on their weight reduction goals, insurance coverage, accessibility during the GLP-1 shortages of branded semaglutide, and socioeconomic factors.

Results

The cohort size was 1,131 patients who were prescribed semaglutide while on the IVIM protocol. A Linear Mixed Effects Model was used to test the relationship between time spent on the IVIM protocol and weight reduction. This model estimated a weight reduction coefficient of -0.739 lbs/week, providing a large z-statistic of -74.02 and a p value < 0.0001. Mean change in weight at 12-weeks for all patients was 14.9 lbs (6.5 %), 24-weeks: 28.6 lbs (12.6 %), 36-weeks: 36.8 lbs (16.4 %), 52-weeks: 45.95 lbs (19.5 %), and those who extended to 68-weeks lost: 46.9 lbs (21.8 %). The percentage of patients who lost at least 5 % of their body weight at 52 weeks was: 99.2 %, 10 % or more: 93.9 %, 15 % or more: 73.5 %, and 20 % or more: 47.8 %.

Conclusion

Patients with obesity completing 52 weeks of the IVIM clinical protocol on semaglutide lost 19.5 % of total body weight with 47.8 % of patients losing 20 % or more. The results of this study indicate the protocol is a novel method to enhance therapeutic medical weight reduction results via a structured, telehealth-based approach for obesity management.

Graphical abstract

1. Introduction

In recent years, the narrative surrounding obesity and the management of this chronic condition has changed. Physicians were traditionally taught little about obesity as a chronic, multifactorial condition and were only educated on managing the downstream complications and comorbidities that typically coincide with obesity, like diabetes and cardiovascular disease. Now, physicians have begun to accept and understand the complex mechanisms of appetite control, the interplay of genetics and environment, and the impact of adipose tissue as an endocrine organ. As such, the use of medication to treat the biological components of obesity has become more widespread and acceptable in the medical community. Patients struggling with obesity often face significant challenges, including societal and healthcare related stigma as well as limited access to effective treatments. The complex interplay of genetic, metabolic, and environmental factors makes sustained weight reduction difficult [1,2]. Obesity is not an issue with willpower; it is a complex metabolic disease with a multitude of demographic, social, economic, and genetic variables which impact its progression [3]. Accordingly, there are now multiple clinical guidelines recommending various anti-obesity medications for those with BMI ≥30 or with a BMI ≥27 with a relevant weight-related comorbidity [4].

Recent therapeutic developments have led to an increase in safe and effective medical weight reduction therapies to treat the underlying causes of obesity, reaching new heights of medical weight reduction results. These innovative therapies have provided new perspective on medical weight reduction and the impact it can have on quality and duration of life. It is largely attributable to the wide acceptance of GLP-1 medications as an effective solution to manage obesity.

Glucagon-like peptide-1 (GLP-1) medications have been revolutionary in the management of obesity, arming healthcare providers with an effective weight reduction therapy that can provide patients with an average weight reduction of 15 % or more. Semaglutide was initially approved for the treatment of type 2 diabetes before receiving FDA approval in 2021 for weight reduction, with an average weight reduction of up to 14.9 % of total body weight at 68 weeks [5]. While GLP-1 medications have been groundbreaking in the management of obesity, they have also been met with criticism regarding their cost and affordability, accessibility as it relates to supply issues, and scarcity of coverage under insurance carriers.

A clinical protocol was developed to deliver Individualized Virtual Integrative Medicine (IVIM) using a telehealth model built to combat the inefficiencies that have hindered the widespread coverage of GLP-1 medications. The clinical care program is meant to deliver high quality, high touch, easily accessible, and data-driven clinical care to drive positive clinical outcomes in patients utilizing GLP-1 medications. This is built on a foundation of streamlined access to the patient's medical care team and a tech-enabled platform to enhance patient education, training, tracking, and community support. This retrospective study shows the clinical benefits that can be derived from continuous GLP-1 therapy administered in a rigorous clinical protocol utilizing a tech-enabled telehealth platform.

2. Methods

Study Design: This retrospective analysis was conducted using a database of patients enrolled with Ivim Health. The outline of the protocol is attached as Appendix A. The protocol is a model for care developed, approved, and supported by a team of board-certified Obesity Medicine physicians. Patients evaluated for inclusion in the study were across 49 states (excluding the state of Mississippi due to telehealth laws regarding medical weight reduction) and were enrolled in the clinical care protocol through the telehealth platform. All participants provided HIPAA consent and provided self-reported information through the HIPAA compliant platform verified by their medical provider via a telehealth consultation.

2.1. Participants/patients

Patients were required to have a body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) of 30 or more. Patients were not excluded for having other health conditions, attempting previous weight reduction medications, or even having previous weight reduction surgery; thus, the patient base is representative of the general population with obesity. Patients excluded from participation included those with relative or absolute contraindications to GLP-1 therapy according to the protocol.

2.2. Procedures

Qualification into the clinical care program through Ivim Health's online telehealth platform was determined for each patient based on BMI and metabolic comorbidities. Patients were screened for absolute contraindications as seen in Appendix A. Upon qualification into the program, patients were assigned a care team comprised of a board-certified obesity medicine physician, board-certified nurse practitioners, nursing staff, certified functional health coaches, and patient experience specialists. Patients were then provided with a telehealth appointment with a medical provider from their care team to discuss various treatment options. Throughout the duration of the program, patients had unrestricted access to their medical provider team. Patients could schedule an unlimited number of video consultations at any time to discuss their medical therapy or call in to nursing staff or their patient experience specialist with questions related to their medical program. Patient care team utilization data can be seen in Table 2.

Table 2.

Utilization data of the care team and technology platform.

	Avg/Percentage	Details
Virtual waiting room utilization	35.4 % of cohort	Over 1/3 of patients utilized the virtual waiting room
Medical consults per month	0.61 consults/month	Medical consultation once every 49 days
Coaching/support Interactions	0.45 interactions/month	Coaching/support team interactions once every 2 months
Total care team interactions	1.06 interactions per month	More than one care team member interaction per month
Online medical dashboard	100 % utilization	All patients interacted with their online medical dashboard
Mobile application (download)	91 % utilization	91 % of patients downloaded and logged into the app at least once
Mobile application (10+ logins)	85 % utilization	85 % of patients utilized the mobile app at least 10 times
Mobile application (monthly utilization)	70 % utilization	70 % utilized the mobile app at least once per month
Average unique day logins	52 unique days	Patients averaged 52 unique days of utilizing the app
Weight tracking	69 % utilization	69 % of patients used the mobile app to track weight
Water intake tracking	36 % utilization	36 % of patients used the mobile app to track water intake
Daily recap utilization	39 % utilization	39 % tracked program adherence with a daily recap
Ivim Health Community enrollment	31 % utilization	31 % of patients enrolled in the community

Table 2: Utilization data was pulled from the telehealth platform to assess care team utilization, defined as utilization of a member of the patient's care team, as well as interactions on the technology platform via the mobile app and the support community.

During their initial consultation with their medical provider, patients were prescribed personalized therapy based on weight reduction goals, insurance coverage, socioeconomic factors and access issues. During the GLP-1 shortages of branded semaglutide, patients were provided the ability to utilize compounded semaglutide from 503A and/or 503B compounding pharmacies utilizing equivalent dosage strengths of the active pharmaceutical ingredient, if medically appropriate, to both establish care and ensure continuity of treatment. In addition to GLP-1 therapy selection, patients were also provided information regarding lifestyle modification, including nutritional interventions and physical activity. More information can be found by review of the protocol. All compounding pharmacies providing medication to Ivim Health patients are 503A or 503B compounding pharmacies based in the United States. Based on 503A/503B regulations, all manufacturers of the semaglutide active pharmaceutical ingredient would be required to have a Drug Master File (DMF) on file with the FDA in order to be utilized by a 503A/503B pharmacy. Further information can be obtained through state pharmacy boards or the FDA who oversee compounding pharmacies.

Patients were encouraged through the Ivim Health mobile app to connect regularly with their medical provider. This was especially true for patients using compounded therapies which required a higher degree of oversight due to the method of injection as they do not utilize a pre-dosed auto-injector. Compounded semaglutide was self-administered by the patient through the use of insulin syringes to draw up from medication vials based upon the providers' dosing instructions. Branded semaglutide was self-administered by the patient using an auto-injector pen. Patients were required to have at least quarterly check-ins with their medical provider in combination with a clinical questionnaire to determine dose titration with each refill that was provided. Patients received personalized titration while following the prescribing information for FDA approved branded semaglutide based on weight reduction results and side effects experienced during their treatment. Patients were initiated at a dosage of 0.25 mg once weekly for 4 weeks and were able to modify their dosing each month as prescribed by their medical provider. Dosage was increased to 0.5 mg, 1 mg, 1.7 mg, and up to the maximum dose of semaglutide (2.4 mg) based on the patient's tolerability and weight reduction results [7]. Some patients experiencing desired weight loss results who preferred to stay on a lower dose or who had side effects that precluded increased titration did not require monthly dose increases.

With each telehealth appointment and refill provided to the patient, weights were self-reported by the patient but verified by their medical provider. A comprehensive analysis of these consultations was performed retrospectively to ensure clinical accuracy of reported data including weight, side effects, adverse event reports, and medication dosing and titration to ensure each patient included in the study followed the clinical protocols.

2.3. Inclusion criteria

To be included in the study, the patient must have completed at least 52 weeks (365 days) of medical management under the IVIM clinical protocols while on GLP-1 therapy with semaglutide. Only patients who were starting at the lowest FDA approved dosing (semaglutide 0.25 mg) and who achieved at some point in time during therapy the highest FDA approved dosing (semaglutide 2.4 mg) were included. For purposes of consistency, patients were only included in the study if they maintained the same medication (brand name or compound) throughout the duration of the study with no gaps in their medical care due to supply constraints present at the time of this retrospective review. In total, there were 1,173 patients meeting this criterion and were evaluated for study inclusion. Of this initial cohort, 42 patients were manually excluded, as detailed in section 2.4, resulting in a final cohort of 1,131 patients as seen in Fig. 1.

Fig. 1.

Patient Data Inclusion Flow Chart

Fig. 1. The number of patients who fit the inclusion criteria for evaluation in the study was 1,173 patients. Upon further clinical review to ensure data accuracy, 42 patients were excluded as they were identified as patients not following the protocols, leaving a final cohort of 1,131 patients.

2.4. Exclusion criteria

Each patient chart where weight history appeared anomalous was manually reviewed by the physician or medical provider serving as the clinical supervisor for the program to ensure data integrity and clinical relevance. This included the 6 % most aberrant weight changes which were manually reviewed and evaluated by at least two medical team members, as well as patients in the top and bottom 3 % of weight reduction results. Through this evaluation, 42 patients were manually excluded based on the following criteria (see Appendix B): failure to maintain treatment for at least 52 weeks, failure to adhere to the IVIM protocol due to gaps in treatment and/or modified dosing from what was prescribed, and the presence of inaccurate or redundant data resulting from duplicate charts and/or human error. These exclusions were necessary to maintain the validity and reliability of the study findings. Following this review process, the remaining 1,131 patients (96.4 % of the original participants meeting inclusion criteria) were confirmed to have clinically relevant and analyzable data. By applying these exclusion criteria, the study cohort was refined to ensure the highest level of accuracy and clinical significance.

2.5. End points and assessment

Coprimary endpoints included change in total body weight at the 52-week interval as well as the proportion of participants achieving a weight reduction threshold of 5 %. Key secondary endpoints identified weight reduction at 12-, 24-, 36-, and 68-week intervals as well as the proportion of participants achieving a weight reduction of 10 %, 15 %, and 20 %. Utilization data of the medical care team, the telehealth platform, and adherence to the protocol was also evaluated. Of note, supply constraints that existed during the timeframe in which this retrospective analysis was assessed excluded patients initiated on branded semaglutide for weight reduction who had to switch to compound intermittently or had gaps in their therapy. Side effects and adverse events were reviewed for the entire cohort of patients, with manual review of all medical escalations (severe side effects or adverse event reports).

3. Statistical analysis

Statistical analysis was performed using Python 3.11.0, and version 0.14.4 of the statsmodels library. The primary estimand was the change in weight reduction over time. Study data was collected from 2023 to 01-01 to 2025-03-31. Given that weight data was self-reported, some participants reported more weights than others. To test the efficacy of the protocol on weight change, (and preserve the highest possible amount of statistical power) we used a Linear Mixed Effects Model, which is resilient against gaps in data. P-value significance was defined as p < 0.05. Average weight reduction per week was regressed over the number of weeks since the study start date (where the start date is roughly equal to the date the medicine arrived at the patient's home or sent to the local pharmacy). A random intercept was incorporated to accommodate the variety in base line weights of study participants. To visualize the impact of the protocol over time, we utilized a six-week moving average for calculated weight reduction. We then calculated a 95 % confidence interval using a bootstrap method to calculate confidence intervals at each week of therapy. This can be seen in Fig. 3. To assess the primary estimand (weight lost at 52 weeks), a dependent paired t-test was performed on a smaller cohort of the original data set (252 participants) defined by patients who recorded both a starting, pre-study baseline weight and a weight within fifteen days of the one-year mark of being on the IVIM protocol. The differences in the efficacy of the protocol between compounded semaglutide and branded semaglutide for weight reduction were also assessed. A Welch's t-test was performed to compare difference in means across groups (442 on compounds, 48 on branded).

Fig. 3.

Average Weight Reduction Over Time on Semaglutide Following Individualized Virtual Integrative Medicine (IVIM) Protocols

Fig. 3: The figure above shows average weight reduction over time, using a 6-week rolling average and bootstrap methods for generating confidence intervals. Confidence intervals grow wider toward the end of the study, reflecting a smaller number of participants reporting weight data at those times.

4. Results

4.1. Patient demographics

As can be seen in Table 1 and Fig. 2A & B, the average age of participants was 44 years; average starting body weight was 228.23 lb; average starting BMI was 37.25. 89.5 % of patients were female and 10.5 % were male. There were 822 patients (72.7 %) with recorded weights up to or beyond the 68-week mark.

Table 1.

Patient demographics.

Average Age:	44 years old
Gender Breakdown:	89.5 % Female/10.5 % Male
Average Starting Weight:	228.25 lb.
Average Starting BMI:	37.25

Table 1: The table above shows the average age, starting weight and BMI as well as the gender breakdown of the study population.

Fig. 2.

Patient age and starting weight

Fig. 2: A: Age distribution of patients included in the study at the time of program initiation are shown. B: Starting weight is defined as the initiation weight of the patient at the time of their first prescription.

4.2. Weight reduction results

Beyond a moving average model to present the data visually, a Linear Mixed Effects Model was used, seen in Fig. 3, to formally test the relationship between time spent on the protocol and weight reduction. This model estimated a coefficient of -0.739, providing a large z-statistic of -74.02 and p-value <0.0001, indicating a strong significance. The proper interpretation of the coefficient is that the model predicts ∼.74 pounds of weight reduction per week.

In the t-test (comparing starting weights to weights at the 52-week mark), results were similarly significant. This test resulted in a large T-statistic of 56.37 and a p-value <0.0001, allowing us to reject the null hypothesis that participants average starting weight is unchanged from study start to a year's worth of participation in the study.

In the Welch's t-test comparing mean difference across groups (compounded semaglutide vs branded semaglutide for weight reduction), the resulting p-value was 0.39; thus, the null hypothesis was unable to be rejected that the groups are distinct, suggesting no statistically significant differences between patients on compounded semaglutide and branded semaglutide for weight reduction when following the protocol.

4.3. Change in body weight

For patients enrolled in the clinical care protocol, weight was monitored throughout the duration of therapy. Weight was self-reported and verified by the medical provider with each medical consultation.

Mean change in weight at 12-weeks for all patients was -14.9 lbs (-6.5 %), 24-weeks: -28.6 lbs (-12.6 %), 36-weeks: -36.8 lbs (-16.4 %), and 52-weeks: -45.95 lbs (-19.5 %). Patients at 68-weeks of therapy lost an average of 46.9 lbs (-21.8 %). These results can be seen in Fig. 4 along with their 95 % confidence intervals displayed.

Fig. 4.

Percentage of Patients Achieving Weight Reduction Milestones

Fig. 4: This figure shows the results of patients achieving specific weight reduction milestones. Over 99 % of patients achieved a weight reduction of at least 5 %. Approximately 94 % of patients achieved weight reduction of 10 % or more with 74 % of patients losing more than 15 % of their total body weight. 48 % of patients lost more than 20 % of their total body weight.

Patients with ineffective weight reduction therapy were patients defined to lose less than 5 % of their total body weight. The percentage of patients who lost at least 5 % of their body weight at 52 weeks was: 99.2 %, or a less than 1 % failure rate. The percentage of patients who lost 10 % or more was: 93.9 %, 15 % or more: 73.5 %, and 20 % or more: 47.8 %. These results can be seen in Fig. 4.

4.4. Medication utilization

Medication selection was determined by the medical provider in discussion with the patient during their initial consultation. Patients were prescribed personalized therapy based on weight reduction goals, insurance coverage, socioeconomic factors and access issues. During the GLP-1 shortages of branded semaglutide, patients were provided the ability to utilize compounded semaglutide from both 503A and 503B compounding facilities utilizing the same dosage strengths of the active pharmaceutical ingredient, if medically appropriate, to both establish care and ensure continuity of treatment. Largely due to the GLP-1 shortage, and in part due to socioeconomic factors regarding cost and affordability, a significant proportion of patients initiated on branded semaglutide for weight reduction were not included in the study due to discontinuation of their therapy, gaps in therapy preventing inclusion in the study, or transition to compounded semaglutide. This resulted in the study having 52 (4.6 %) patients on branded semaglutide for weight reduction while 1079 (95.4 %) patients were on compounded semaglutide (see Fig. 5). Mean change in weight for patients with compounded semaglutide vs. branded semaglutide at 12-weeks was –17.0 lbs (-7.6 %) vs. –8.6 lbs (-4.0 %), 24-weeks: -29.8 lbs (-13.5 %) vs. -25.8 lbs (-11.5 %), 36-weeks: -38.7 lbs (-17.6 %) vs. -33.0 lbs (-15.9 %), 52-weeks: -46.3 lbs (-20.3 %) vs. -38.7 lbs (-17.9 %), and 68-weeks: -46.8 lbs (-21.1 %) vs. -51.6 lbs (-22.9 %). However, these values should not be used to compare compounded semaglutide for branded semaglutide, given the small number of branded treated semaglutide patients and given this was not a controlled comparative study.

Fig. 5.

Medication Utilization

Fig. 5: This figure shows the percentage of patients on compounded semaglutide (95.4 %) vs. branded semaglutide for weight reduction (4.6 %). These numbers were largely impacted due to the supply shortages of branded Semaglutide for weight reduction during the study, causing many patients to have disruptions in their medical therapy and thus not being eligible for inclusion in the study.

4.5. The individualized virtual integrative medicine (IVIM) model: care team and platform utilization

Utilization of the medical care team as well as the technology platform for patients on the protocol was monitored throughout the duration of therapy. To understand the volume of interactions with each patient's medical care team as well as utilization of the platform, all medical data of each interaction was collected and analyzed within the electronic health record while website, mobile app, and community interactions were measured within a separate data warehouse.

For the protocol, patients were required to interact with their medical provider at least once every 3 months. Patient visits with a provider were used for initiating therapy, tracking progress, monitoring side effects, adjusting dosage of medication and discussing ongoing lifestyle changes. On average, patients on the protocol engaged in 0.61 medical consults per month or engaged in a consultation once every 49 days. Patients also had access to a virtual waiting room for immediate access to a medical provider to discuss their treatment program. Approximately 35.4 % of patients utilized this route of consultation during the course of their therapy. In addition to the medical provider, patients had access to patient experience representatives to deal with non-medical issues, nursing representatives for triage of medical questions, as well as functional health coaches for lifestyle recommendations and optimization. On average, patients interacted with these members of the care team approximately once every 2 months (0.45 interactions per month). This led to an average of 1.06 total interactions per month with a member of the patient's care team or 12.72 interactions extrapolated over a 52-week period.

Platform utilization was also monitored throughout the treatment program. All users had access to and utilized the online telehealth platform for registration and scheduling medical consultations. All patients had access to and utilized their online medical dashboard during the course of therapy. Ninety-one percent of patients utilized the mobile app at any time during the course of therapy with over 85 % using the app a minimum of 10 times. On average, each patient logged in to the mobile application on 52 unique days, 69 % of patients used the weight tracking feature, 36 % of patients used the water intake tracking feature, and 39 % of patients used the daily recap feature, a feature designed to track patient feedback on daily program adherence. Approximately 70 % of patients utilized the mobile app at least once per month throughout the duration of their program.

As a part of the platform, the telehealth community was an optional feature patients could enroll in to gain access to like-minded individuals and to find support from other patients on their health and wellness journey. Approximately 31 % of patients enrolled in the community.

4.6. Side effects & adverse events

Side effect data was self-reported and was collected during each consultation as part of the protocol. Medical providers used side effect data in determining the appropriate dosing titration for the patient. The most common side effects were constipation (203 patients), followed by nausea (176 patients), fatigue (135 patients), and diarrhea (59 patients). The majority of patients had minimal (51.24 %) or moderate but manageable side effect profiles (43.8 %). The presence of severe side effects was only present in 3.3 % of patients, with 1.65 % not reporting the severity. A total of 293 (27.2 %) patients on compounded semaglutide and 9 (17.3 %) patients on branded semaglutide for weight reduction reported side effects at some point throughout their duration of therapy.

Adverse events were reported and followed up utilizing a strict medical escalation protocol. See Appendix A for more information. The total number of adverse event reports during the study was 20. The most frequently reported adverse events associated with side effects were gastrointestinal in nature. Of the 20 identified adverse events, 2 were determined to be unrelated to GLP-1 therapy. Those included a patient who experienced a fainting episode which was determined by cardiology to be vasovagal in nature, and a patient who developed altered mood which was determined to be a result of worsening underlying depression. The total number of patients experiencing an adverse event on compounded semaglutide was 19 (1.76 %) and branded semaglutide was 1 (1.92 %).

In July of 2024, the FDA issued an alert cautioning medical providers about the potential for adverse events related to patient self-dosing of compounded medication [6]. The clinical care model employs a system in which patients are given clear and easy-to-understand dosing instructions through several modes of communication and access to immediate provider support. As such, the adverse events related to dosing errors in this study were found to be exceedingly low; 14 occurrences of 1079 patients included in this study, or 1.30 %. This is likely due to the inclusion criteria utilized, potentially causing underreporting of severe side effects and adverse events as those patients may have discontinued treatment early. Side effect and adverse event data are presented below in Fig. 6 & Table 3.

Fig. 6.

Incidence and severity of side effect profiles

Fig. 6: Side effect profiles are shown above. The most common side effects were GI-related. For the vast majority of patients (over 95 %), side effects were reported as minimal or moderate but manageable. Only 3.3 % of patients noted severe side effects during therapy.

Table 3.

Adverse event data reported through the medical escalations protocol.

	Compounded Semaglutide		Branded Semaglutide
	#	% (n = 1079)	#	%(n = 52)
Participants with ≥1 adverse event during treatment period	19	1.76 %	1	1.92 %
Death	0	0.00 %	0	0.00 %
Serious adverse events	0	0.00 %	0	0.00 %
Adverse events leading to discontinuation of treatment	3	0.28 %	0	0.00 %
Dosing errors	14	1.30 %	0	0.00 %
Adverse events determined not due to GLP-1 medications	2	0.19 %	0	0.00 %

Table 3: Adverse event data is shown. Adverse events are minimal and thus no statistical comparisons were made amongst the study group. Only 20 adverse events occurred in the study population (1.7 %). Specifically, in the group of patients on compounded medication, most adverse events were related to self-administered dosing errors (occurring in 1.30 % of the total patients on semaglutide).

5. Discussion

Patients on once weekly semaglutide therapy following the clinical protocols lost an average of 19.5 % total body weight after 52 weeks on treatment. Most semaglutide efficacy studies utilize a 68-week course of treatment, thus this study analyzed a smaller cohort of 822 patients who also completed a 68-week treatment regimen. These patients lost 21.8 % of their total body weight.

5.1. Weight reduction outcomes achieved on the protocol with semaglutide

The successful weight reduction results seen in patients on the clinical protocol may be due to a combination of factors. The clinical protocol involves medical management titrated to meet individual patient needs as well as tailored and customized lifestyle modifications. This allows patients to have access to a medical provider and health coaching staff to personalize therapy, including nutritional interventions and physical activity, on an individual basis (as seen in the utilization data in section 4.5). In addition, it allows medical providers to more closely provide dosing modification in real-time to limit side effects and enhance therapeutic results [8], [9].

Patients enrolled in the protocols are also enrolled as members of the telehealth community, a social network of patients who are on a weight reduction journey through the platform and a construct for offering emotional support. Studies have shown that social support, including through online platforms, can have a significant impact on weight reduction outcomes [10], [11]. In fact, in a study in bariatric surgery patients, frequent versus infrequent or non-users of social media support groups had higher overall weight reduction in the first 2 years of their journey [12]. Patients enrolled in the community (approximately 31 % of the study population) have access to social support including community events for education, question and answer sessions, as well as group nutrition and meal planning that may aid in overall weight reduction treatment outcomes. This may lead to improved weight reduction outcomes through the social support network, as has been identified in other studies.

Finally, patients enrolled in the protocols have access to a tech-enabled platform, allowing for streamlined communication with their medical care team. This is integrated through the mobile application which allows for weight tracking, the incorporation of biometric devices, including common Apple and Android applications, education and access to the community, dosing instructions that can be modified in real-time by the medical provider, and access to a real-time chat to engage with patient experience or medical representatives to ensure patient inquiries are handled quickly and efficiently. The study group was found to be highly engaged with the tech-enabled platform as well as through video visits with their care team. Patients were scheduling visits with their provider once every 7 weeks on average and utilized the app several times a month with the majority of participants using this platform to track their weight. This highlights the importance of communication due to the high level of support patients require when utilizing injectable medications, especially if using compounded formulations that are not as simple to administer as auto-injectable pens.

This study supports a multifaceted approach that may provide an advantage to a patient's success on their medical weight reduction journey. Overall, the clinical protocols demonstrate a successful, structured, safe, telehealth-based approach for obesity management with GLP-1 therapy.

6. Limitations

There are two primary limitations to this study. The first is the retrospective nature of the study which limits reliance on data based on the potential for bias (selection, recall, misclassification) and challenges in controlling for confounding variables that would be limited in a randomized control trial. The second limitation of the study is the self-reported data which may present inaccuracies in the data set. The use of inclusion/exclusion criteria as above could have resulted in some selection bias, especially as it relates to side effects and adverse event reports as the requirement to complete a year of therapy would potentially exclude a subset of these patients. In addition, there exists the inherent possibility of underreporting based on the self-reporting system utilized. The intensity of the medical protocols regarding patient tracking as well as the methods utilized to exclude obviously aberrant data helped to mitigate these limitations. Comparisons between branded semaglutide for weight reduction and compounded semaglutide are limited because of the relatively small number of patients able to obtain and maintain branded semaglutide therapy primarily due to insurance coverage and supply issues. This analysis is limited due to semaglutide no longer being in shortage and, as of May 22, 2025, the FDA determined that U.S. pharmacies and clinics were no longer allowed to compound and sell essential copies of semaglutide [13].

7. Future directions

While the results of this study support the individualized virtual integrative medicine (IVIM) approach, it is important to note that more investigation must be done. Further study is needed to evaluate the impact of the IVIM protocol with GLP-1 medications on weight reduction as compared to GLP-1 medications alone. Randomized controlled trials isolating the four pillars of the protocol should be further pursued to understand the individual impact of each pillar. Also, a larger intention-to-treat cohort analysis could be considered to review side effect and adverse event data that may not be included in this study. Certainly, further study and comparison of compounds with brand name medications will be necessary for clarity regarding safe and appropriate use. Lastly, a similar study assessing results of patients utilizing tirzepatide formulations would give broader context to the overall benefit of the protocol. The addition of these investigations to the collection of research would result in a more complete understanding of the role of the protocol and GLP-1 medications in weight reduction.

8. Conclusion

The results of this study indicate the clinical protocol is a novel method to enhance therapeutic medical weight reduction results via a structured, telehealth-based approach for obesity management with GLP-1 therapy. The protocol supported the following:

• ●This study showed a weight reduction of 21.8 % (46.9 lbs) at 68 weeks
• ●The clinical protocols as well as the individual and social support provided to patients play a pivotal role in achieving successful weight reduction outcomes.
• ●The protocol aids in preventing dosing errors of GLP-1 medication, improves medication adherence and improves patient outcomes through a personalized and tailored approach to each individual patient.

Authorship contribution

Authorship and study design was initiated by TK. Statistical analysis was performed by JM. TK, JD, PLS, JN, and ALL manually reviewed data. TK, JD, PLS, EB, CF, JN, and ALL reviewed, edited, and approved the final submission for publication.

Disclosures

All authors have no conflicts of interest to disclose including no personal relationships that influenced the work in this manuscript. All authors except for TK are salaried employees of Ivim Health but have no additional financial interests in Ivim Health. TK is cofounder and CMO of Ivim Health and as such holds financial interests with Ivim Health.

Ethical adherence and review

The greatest level of ethical adherence was taken during this retrospective analysis. Patient confidentiality and ethical treatment of all data was maintained to the highest degree. Unless otherwise stated, responsibility for editorial decisions and peer review process for this article was delegated to non-author Editors or non-author Associate Editors.

Declaration of artificial intelligence (AI) and AI-assisted technologies

During the preparation of this work the authors did not use AI.

Source of funding

Funding for this study was solely provided through Ivim Health. Beyond payment to the research staff by Ivim Health this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Appendix A.

The IVIM Clinical Protocol: Individualized Virtual Integrative Medicine

The IVIM Clinical protocol is rooted in the belief that care should be accessible, holistic and personalized to each individual patient. By fostering a partnership with their team of medical providers, each patient establishes a patient-provider relationship designed to deliver the highest quality of care through compassion, empathy, and personalized therapy that includes safe and effective medications as well as additional support through functional health coaching and a wellness community. Through the use of an integrated technology platform and mobile application, patients have more overall engagement and feedback needed to propel them along their wellness journey. The IVIM Clinical Protocol is comprised of the following 4 Pillars which work in tandem to maximize results, minimize barriers to treatment and create a positive overall patient experience: medical management, functional health coaching and support, a wellness community, and access to a tech-enabled medical platform.

Pre-enrollment into the IVIM program:

Patients considering enrollment in the IVIM clinical protocols are required to complete a dynamic eligibility form to determine eligibility for the medical therapy. Eligibility for the IVIM GLP-1 program requires:

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  Patients to have a BMI:

  • o
    30
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    Or >27 with a metabolic comorbidity
• -Age of 18 or older
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  No absolute contraindications to GLP-1 therapy:

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    Primary family history of medullary thyroid cancer
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    Family history of MEN-2 syndrome
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    Previous diagnosis of gastroparesis
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    Previous diagnosis of pancreatitis (unless the offending reason has been managed, i.e. gallstone pancreatitis status post cholecystectomy)
  • o
    No history of diabetic retinopathy
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    Not currently pregnant or breastfeeding
• -Review of relative contraindications
• -Review of past medical history (including medical, surgical, and relevant family history)
• -Review of medications
• -Review of previous or current medical weight loss treatments
• -Review of non-medical weight loss treatments/programs

Enrollment into the IVIM program:

Enrollment into the IVIM program is determined based on medical provider review of the eligibility form as well as a medical consultation with the prospective patient to determine appropriate therapeutic options. For patients medically qualified to enroll in the IVIM program, the following aspects of medical weight loss therapy are discussed with their medical provider during their first medical consultation:

• -Medical history documented within their intake form
• -Past attempts at non-medical weight loss
• -Past attempts using medical weight loss
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  Available GLP-1 therapies

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    Evidence based assessment of anticipated medical weight loss results
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    Discussion regarding potential side effects and rates of occurrence
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    Discussion regarding potential adverse events and rates of occurrence
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    Socioeconomic variables regarding cost of therapy

    • ⁃
      This includes an insurance assessment for potential coverage

      • •
        Benefits verification and prior authorization submission for patients eligible for GLP-1 coverage through their insurer
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  Lifestyle elements focused on throughout the IVIM program

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    Nutritional elements:

    • ⁃
      Minimal focus on calorie counts and caloric restriction
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      Heavy focus on macronutrient profiles

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        High protein dietary preference
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        High fiber dietary preference
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        Minimizing simple sugars
    • ⁃
      Dense macronutrient foods to counterbalance reduced dietary intake while on GLP-1 therapy
    • ⁃
      Hydration goals based on gender and body weight
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      Supplement optimization based on individual dietary preferences
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    Exercise elements:

    • ⁃
      A core focus on enhancing overall activity and increasing over time based on the patient's baseline
    • ⁃
      Recommendation for combination of both cardiovascular exercise and strength training with focus on enjoyable, convenient activity to maximize adherence
    • ⁃
      No stringent or defined requirement for exercise activity
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    Sleep and mental health

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      Raising awareness on the impact of sleep and stress levels as it relates to weight maintenance optimization
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  Utilization of the technology platform to enhance results

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    Mobile application downloads with brief training and teaching on utilization of the mobile app for tracking, nutritional advice, and access to the IVIM care team
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    Encouragement for patient tracking of weight loss and lifestyle components for enhanced coaching
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    Easy access point for scheduling appointments and communicating with the medical care team
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  Utilization of the community for emotional support and enhanced accountability

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    Enrollment into the IVIM community
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    Emotional support features and identification of common groups (PCOS, diabetes, hypothyroidism, etc.)
• -What to expect while on the IVIM program
• -Selection of medical therapy and dosing
• -Dosing and administration instructions
• -Guidance on injectable therapies

Active monitoring on the IVIM protocol:

All patients enrolled in the IVIM protocol received access to active monitoring throughout the duration of the program. This was done to ensure patient safety and appropriate medication utilization. Active monitoring while on the IVIM protocol includes the following:

• −
  Contact with medical team at least every three months to evaluate for adherence, progress, and tolerability of current medication regimen which includes:

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    Dosage of medication and date last taken ensuring medication taken as prescribed
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    Most recent weight, effects noted from medication, and any desire for change in dose.
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    Disclosure of any side effects including severity
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    Report of any other comments or medical history changes the patient may have had since the previous interaction
• −Weekly prompted check-ins through the IVIM mobile app to assess program and ensure side effect mitigation
• −Access to the IVIM mobile app and patient dashboard to easily initiate real-time chat with dedicated patient experience team members

Side effects, adverse events, and medical escalations on the IVIM protocol:

The IVIM protocol outlines a procedure for medical escalations to thoroughly and expediently triage and manage any patient with severe side effects, dosing errors, or adverse events. Medical escalation protocol is initiated in the following circumstances:

• -A patient has had a severe side effect or adverse event
• -A patient has dosed or titrated inappropriately on more than one occasion
• -An order error has occurred regardless of patient outcome

If any of the above occurs, the provider who is conducting the visit with the patient or reviewing the asynchronous message from the patient initiates the medical escalation protocol which includes:

• -Notifying the lead nurse practitioner or physician for the patient's state
• -Creating a Medical Escalation appointment for the patient
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  Nursing team follow up

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    Call patient 24 and 48 h after visit to follow up on patient progress, any in person evaluation or testing that was done
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    Nursing team reports back to lead nurse practitioner or physician with follow-up information

For any patient who presents for a visit or sends an asynchronous message to notify a provider that they have had an emergency room visit or a hospitalization, regardless of reason or diagnosis the following steps are taken:

• -Medical escalation protocol above is initiated
• -
  Tracking form is completed

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    Tracking form includes all relevant patient information, GLP-1 medication, most recent dose and details regarding ER visit/hospitalization, any testing or consultations that were performed and any diagnoses made
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    Tracking form populates to a tracking board for further review
• -
  All ER visits and hospitalizations are reviewed by a Clinical Manager and the Medical Director on the tracking board twice a day. This is done to:

  • o
    Provide additional guidance and instructions for follow-up or continuation of care as needed
  • o
    Contact patient or schedule additional follow-up visit if needed
• -All ER visits and hospitalizations are reviewed by the Medical Director and Chief Medical Officer weekly

The core components of the IVIM protocol:

The IVIM protocol is based on four pillars of support:

• 1.Medical Management
• 2.Functional Health Coaching Support
• 3.Wellness Community
• 4.Technology Platform

The four pillars of the IVIM protocol are integral to the therapeutic strategy selected and continued therapeutic optimization throughout the course of the patient's medical therapy. Patients on the IVIM protocol have access to the four pillars at all points in time of their therapeutic program. Not only is it critical for these variables to be available, but also readily accessible to offer the right solution at the right time for the patient. Details of execution of these four pillars are proprietary to Ivim Health™.

• 1.Medical management: Every patient is provided with a medical care team to support their health and wellness journey. The medical care team consists of a board-certified obesity medicine physician as well as a team of board-certified nurse practitioners.

Patients can schedule an unlimited number of 15-min video consultations with a member of their medical care team. In addition, patients have access to a virtual waiting room during normal business hours to immediately connect with a member of the medical team. Each virtual consultation focuses on the core concepts proposed in the enrollment section while also engaging with patients to answer questions related to both their medical therapy as well as lifestyle components.

• 2.Functional Health Coaching Support: Functional health coaching aims to identify the root-cause and lifestyle components which may be contributing to the patient's cardiometabolic syndrome. Through this root-cause approach, functional health coaches discuss nutrition, exercise, stress, and overall mental health with each patient to identify methods of incorporating small, incremental lifestyle change to achieve greater success within their medical program.

Nutrition coaching focuses on balanced, nutrient dense eating while limiting focus on caloric restriction. Exercise is primarily focused on enhancing movement throughout the day, picking up at the patient's current physical activity level and engaging in small, incremental increases in physical activity recommendations. Education is provided on the impact stress and optimizing mental health can have on weight loss success and maintenance. Sleep is a key component, focusing on appropriate sleep hygiene and being aware of current stress levels.

By incorporating small lifestyle changes over time, patients are more likely to achieve greater weight loss results while also being able to maintain those weight loss results over time. The functional health coaching program focuses on small, incremental changes to achieve lasting results.

• 3.Wellness Community: Research has shown greater weight loss success stories for patients who have a support system in place to both encourage them and hold them accountable to their weight loss program. Patients on the IVIM protocol are enrolled in and may engage in a community of patients on a similar weight loss journey. In addition, patients can find groups of patients with similar medical comorbidities or other conditions. Patients can engage with other individuals on the program, discuss medical weight loss results, ask questions, and obtain support throughout their medical program. In addition, weekly live question and answer sessions are held with a member of the functional health coaching team to provide education and training. The community is overseen by patient experience representatives and functional health coaches who help engage with patients, moderate groups, and escalate any medical issues noted within the community.
• 4.Technology Platform: Each patient enrolled in the IVIM protocol does so through a tech-enabled platform. This platform records every engagement of the patient within the IVIM program while also providing direct access to the medical care team, functional health coaches, insurance authorization team, and patient experience specialists.

Integral to the technology platform is a mobile application. Within this application, patients can connect biometric devices and wearables (Apple health and Android devices/apps), track program progress (weight, macronutrients, water intake, etc.), utilize a daily questionnaire to assess program adherence, and access nutritional, exercise, and programmatic resources to fully engage with their medical program.

The goal of the IVIM clinical protocols for GLP-1 therapy is to optimize outcomes while mitigating and limiting potential side effects and adverse events. Patients enrolled in the IVIM program have unlimited accessibility to their medical care team through optimal means of communication, such as virtual video consults, while also having access to best-in-class medication options. Through personalized support, enhanced access to the medical team, functional health coaching providing a root-cause analysis to optimize lifestyle modification, an optimized patient experience through a tech-enabled platform, and access to gold standard medical therapies, patients on the IVIM GLP-1 protocol have the core components required to provide maximal weight loss outcomes.

Appendix B. List of Exclusions

Reason for Exclusion	Reason for Exclusion
Failure to adhere to the protocol due to gap in treatment	12
Failure to maintain treatment for at least 52 weeks	14
Presence of inaccurate or redundant data resulting from duplicate charts	2
Failure to adhere to the protocol due to modified dosing	12
Presence of inaccurate or redundant data resulting from human error	2
Total	42

Appendix C. Supplementary data

The following are the Supplementary data to this article: