Development of a Follow-Up Protocol for Patients Treated with Injectable Semaglutide for Weight Loss: Design of a Research Study in Community Pharmacy

Abstract

In 2024, a second brand of injectable semaglutide was marketed, authorized for the indication of weight loss, along with the first tirzepatide. Both are indicated as an adjunct to a low-calorie diet and increased physical activity for weight control, including weight loss and maintenance, in adults with a BMI greater than 27. In Community Pharmacy, we have a Professional Pharmaceutical Service in Nutrition, and it is of interest to study and compare the outcomes obtained by patients using these drugs versus those who only adopt lifestyle changes in diet and physical activity. This is especially relevant after observing that several patients had stopped attending the Nutrition Service, arguing that maintaining diet and increasing physical activity required too much effort, and that they would instead request a prescription for one of these drugs from their primary care physician.

A protocol was therefore designed to conduct a research study during 2026 to allow follow-up of patients treated with injectable semaglutide and tirzepatide, since during the dispensing of these medicines it was detected that patients lacked knowledge regarding possible adverse effects and the dietary and physical activity habits they should maintain during treatment. The most frequent adverse effects are gastrointestinal: nausea, vomiting, diarrhea, constipation, abdominal pain; others may also appear such as headache, dizziness, and fatigue, and cases of retinopathy, hypotension, cholelithiasis, and hair loss, among others, have been reported.

Data collection will take place during 2026 through various questionnaires and/or interviews with patients who agree to participate in the study. Different questionnaires will be developed to collect important information at each phase of treatment, as well as the outcomes obtained in terms of weight loss and lifestyle habits adopted after initiating pharmacological treatment, in order to perform a statistical analysis of the variables.

The main objective of the research will be to assess the results obtained over one year regarding weight loss in patients treated with semaglutide or tirzepatide, as well as adverse effects and, where applicable, rebound effect, and to compare them with the results obtained in other patients from the nutrition service who are not receiving these treatments. With the data obtained, statistical analyses will be carried out to describe the sample, using absolute and relative frequencies for qualitative variables, and means and standard deviations for quantitative ones. Chi-square tests will also be used to compare proportions regarding weight loss, adverse effects, weight maintenance or rebound, and dietary and exercise habits adopted by patients treated with semaglutide or tirzepatide compared with those not using these drugs.

In addition, potential DRPs (Drug-Related Problems) and NMOs (Negative Medication Outcomes) will be studied, and health education will be provided, emphasizing the importance of acquiring healthy dietary and physical activity habits.

INTRODUCTION

In 2020, 17.5% of the adult population in the Canary Islands was classified as obese (1). Although these figures have remained stable, the proportion continues to be high, and community pharmacies must play an active role in providing health education on healthy lifestyle habits with the goal of reducing rates of overweight and obesity.

Obesity is associated with comorbidities such as type 2 diabetes, hypertension, and cardiovascular disease (2), as well as a significant health and economic impact (4). These conditions entail substantial healthcare expenditure, and reducing their prevalence could not only improve individuals quality of life but also alleviate the financial burden on the National Health System.

In 2024, a second pharmaceutical formulation of semaglutide was approved in Spain for the indication of weight loss. Semaglutide is a GLP-1 analogue, sharing 94% homology with human GLP-1, and acts as an agonist of its receptor. This mechanism promotes a reduction in caloric intake by increasing satiety, decreases appetite by modulating hypothalamic centers involved in eating behavior regulation, and contributes to improved glycemic control —making it particularly valuable for patients with overweight and obesity. Clinical trials have demonstrated its efficacy in reducing body weight, improving cardiometabolic parameters, and maintaining weight loss long-term.

Tirzepatide is a dual agonist of the GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 receptors, representing an innovative mechanism of action compared to isolated GLP-1 analogues. This combined action enhances the incretin effect, promoting caloric reduction by increasing satiety and decreasing appetite, while also improving insulin secretion and sensitivity, thereby contributing to glycemic control. Clinical trials from the SURPASS and SURMOUNT programs have demonstrated superior efficacy compared with other GLP-1 agonists in reducing body weight, accompanied by improvements in cardiometabolic parameters —including glycemia, lipid profile, and blood pressure— with sustained long-term weight reduction.

From the community pharmacy, implementing a structured follow-up protocol allows for the evaluation not only of the efficacy and safety of treatment with semaglutide and tirzepatide, but also of the acquisition of healthy eating and physical activity habits —an essential aspect for sustaining results and preventing relapse.

OBJECTIVES

Main objective

To evaluate weight loss, the presence of adverse effects, and the occurrence of rebound effect in patients treated with injectable semaglutide or tirzepatide, comparing them with patients receiving nutritional counseling without pharmacological treatment.

Secondary objectives:

• To analyze the evolution of eating and physical activity habits in both groups.

• To study the relationship between sociodemographic variables and weight loss outcomes.

• To identify and classify Drug-Related Problems (DRP) and Negative Outcomes associated with Medication (NOM).

• To describe the dispensing of semaglutide and tirzepatide during the study period.

MATERIALS AND METHODS

1. Study design

This will be a quasi-experimental study in which the results obtained after analyzing the variables will be compared.

2. Study setting

Temporal scope: Data collection will be carried out during the year 2026.

Spatial scope: Community Pharmacy.

3. Study population

Prior to initiation, approval will be requested from the Research Ethics Committee for Medicines (CEIm), as the study involves the collection of clinical data from patients.

Inclusion criteria:

• Patients over 18 years of age who come to the community pharmacy to collect an injectable semaglutide or tirzepatide medication prescribed for weight loss.

• Patients over 18 years of age enrolled in the pharmacy’s Nutrition Service who are not receiving semaglutide or tirzepatide treatment.

• Patients who agree to participate by signing the informed consent and data protection forms.

Exclusion criteria:

Patients with conditions that may hinder the follow-up of the study (e.g., psychiatric disorders).

4. Sampling design

The sample will consist of all patients who come to the community pharmacy during 2026 for the dispensing of any medication containing semaglutide for the indication of weight loss and who wish to participate in the study.

5. Information sources

The questionnaires used have been designed and adapted from models employed in previous studies on nutrition and obesity, allowing standardized data collection on lifestyle habits, medical history, anthropometric measurements, and treatment adherence. The administration of questionnaires will be carried out by a community pharmacist trained in nutrition, ensuring homogeneity and reliability in data collection.

The information required for data analysis and result generation will be obtained from these designed questionnaires.

Visits will be scheduled every 4 weeks until reaching the maintenance dose of 2.4 mg, and at each visit, interventions will be conducted as shown in Table 1.

Depending on the adverse effects experienced by the patients, they may remain at the same dose for a longer period without advancing. In such cases, a follow-up visit will also be conducted to verify the results obtained and perform pharmacotherapeutic monitoring.

Table 1.

Semaglutide Visit Schedule

VISITS	QUESTIONNAIRES
Visit 1. Starting Dose 0.25 mg. Weeks 1–4	Informed consent Data protection Initial interview Anthropometric measurements Pharmacotherapeutic follow-up
Visit 2. Dose 0.5 mg. Weeks 5–8(The dose is only increased if the response is not positive)	Follow-up interview Anthropometric measurements Pharmacotherapeutic follow-up
Visit 3. Dose 1 mg. Weeks 9–13(The dose is only increased if the response is not positive)	Follow-up interview Anthropometric measurements Pharmacotherapeutic follow-up
Visit 4. Dose 1.7 mg. Weeks 14–16(The dose is only increased if the response is not positive)	Follow-up interview Anthropometric measurements Pharmacotherapeutic follow-up
Visit 5. Dose 2.4 mg. Maintenance dose(The dose is only increased if the response is not positive)	Follow-up interview Anthropometric measurements Pharmacotherapeutic follow-up

6. Variables

Table 2.

Variables

Category	Variables
Sociodemographic variables	Age Sex Date of birth Employment status Education level
Lifestyle variables	Sleep habits Time dedicated to physical activity Tobacco use Alcohol consumption
Clinical history variables	Menstrual cycle (in case of women) Pregnancy Bowel habits Blood pressure Current or past diseases Family history Surgeries Pharmacological treatment and/or supplementation
Dietary pattern and eating behavior variables	Dietary pattern and eating behavior variables Diets or eating patterns followed Barriers to healthy eating Emotional state Foods disliked or poorly tolerated Food diary
Anthropometric measurement variables	Weight Height BMI % body fat % body water Muscle mass Hip circumference Waist circumference Bicipital skinfold Tricipital skinfold Abdominal skinfold Suprailiac skinfold
Pharmacotherapeutic follow-up variables	Health problem(s) Medication(s) in use Dosing regimen
Dispensing variables	Active ingredient and dispensed dose Treatment initiation or continuation Review of contraindications Health education provided

Table 3.

Tirzepatide visit schedule

Week	Tirzepatide dose	Observations / Visit
0–4	2.5 mg/week	Start of treatment. Evaluation of tolerance and gastrointestinal adverse effects.
5–8	5 mg/week	Review of weight, adverse effects, and adherence.
9–12	7.5 mg/week	Clinical reassessment and reinforcement of health education.
13–16	10 mg/week	Assessment of efficacy and tolerability. If the desired effects are achieved, this dose may be maintained without further titration.
17–20	12.5 mg/week	Continued follow-up, detection of DRP/NRM. Increase the dose only if goals are not achieved.
21–24	15 mg/week	Global evaluation of efficacy and safety. Maintain only if greater weight loss is required.
>24	Maintenance 5–15 mg/week	Adjust the dose to the minimum effective and best-tolerated level according to response and adverse effects. Periodic reviews.

7. Statistical

The open-access statistical software R-Commander will be used to perform various analyses:

• To describe the sample by calculating absolute and relative frequencies for qualitative variables, and means and standard deviations for quantitative variables.

• To compare the results obtained in patients treated with semaglutide versus those not using the drug, the Chi-square test for comparison of proportions will be applied. To compare mean weights, the Student’s t-test will be used.

A value of p<0,05 will be considered statistically significant.

EXPECTED RESULTS

Sufficient data will be collected to allow statistical analysis and comparison of outcomes in patients treated with the study drugs versus those receiving nutritional counseling without pharmacological treatment for obesity. The following aspects will be evaluated:

1. Clinical efficacy of treatments

• Absolute and relative weight loss (% of initial weight).

• Changes in BMI and nutritional classification.

• Comparison of efficacy: semaglutide vs tirzepatide vs control group.

• Impact on metabolic parameters: blood glucose, lipid profile, blood pressure, uric acid (if laboratory data are available).

2. Safety and tolerability

• Incidence of adverse effects (nausea, vomiting, diarrhea, constipation, reflux, etc.).

• Adherence and persistence to treatment (discontinuation due to adverse effects or lack of efficacy).

• Events related to dose escalation (improved tolerance when maintained at intermediate doses).

3. Lifestyle and health behaviors

• Changes in physical activity: sedentary versus active time.

• Sleep habits: quality, number of hours, awakenings.

• Tobacco and alcohol consumption: evolution throughout treatment.

4. Eating behavior and nutritional adherence

• Changes in meal frequency, quality, and intake of vegetables, fruits, proteins, and processed foods.

• Identification of emotional factors associated with eating (anxiety, boredom, stress).

• Reasons for abandoning previous diets and comparison with the current regimen.

• Impact of medication on hunger and satiety sensations.

5. Quality of life and psychosocial sphere

• Emotional status (stress, sadness, motivation).

• Employment situation and impact of schedules on habits.

• Patient’s perception of treatment success (personal goals achieved).

6. Pharmaceutical outcomes (DRP and NROM)

• Drug-Related Problems (DRP): lack of adherence, dosing errors, incorrect dose.

• Negative Results associated with Medication (NROM): inefficacy, undesired adverse effects, treatment discontinuation.

• Evaluation of pharmaceutical interventions in the prevention and resolution of DRP/NROM.

DISCUSSION

Overweight and obesity represent a major public health problem with high prevalence, associated with increased comorbidities such as type 2 diabetes, hypertension, dyslipidemia, and cardiovascular disease, as well as a substantial economic impact on the healthcare system. The development of follow-up protocols within community pharmacies provides evidence on the applicability of innovative treatments such as semaglutide, integrated into a multidisciplinary approach to obesity.

The expected results of this project will allow assessment, beyond clinical efficacy, of the usefulness of community pharmacy follow-up in terms of detecting Drug-Related Problems (DRP) and Negative Results associated with Medication (NROM), as well as identifying barriers to adherence and preventing adverse effects. The community pharmacist plays a key role in supporting patients in lifestyle modification, emphasizing the importance of a balanced diet and physical activity as fundamental pillars for long-term weight maintenance.

Furthermore, the study will yield valuable insights into the sustainability of weight loss achieved with these treatments, the frequency of rebound effects after treatment discontinuation, and patients’ perceptions of their therapeutic process. All of this contributes to better planning of future interventions from community pharmacies, with both clinical and economic benefits for the healthcare system.

In conclusion, this proposal not only provides data on a highly relevant and current medication but also highlights the value of the community pharmacist in the comprehensive management of obesity, reinforcing their role within the multidisciplinary healthcare team and emphasizing their potential to improve clinical outcomes, patient quality of life, and healthcare system sustainability.

APPENDIX.

Annexes