The Efficacy and Dosage of Semaglutide for Weight Loss

1. Introduction to Semaglutide

Semaglutide is a GLP-1 receptor agonist that was developed as a treatment for type 2 diabetes. Although initially in development for that indication, there has been a quest to develop medications effective for weight management. The recognition that certain drugs used in diabetes care are often associated with weight loss led to the re-evaluation of these agents for weight management. Semaglutide for the treatment of obesity has been approved for adults with either a body mass index (BMI) of 30 kg/m² or more, or a BMI of 27 kg/m² or more, with a weight-related comorbidity, such as type 2 diabetes, hypertension, dyslipidemia, or obstructive sleep apnea, for use as an adjunct to a reduced-calorie diet and increased physical activity.

When considering Semaglutide as a medication for weight loss, it is important to understand how it achieves its effect. The multiple enzyme interactions and hormonal influences of the body can provide a variety of weight-lowering effects at different levels. Some therapies may have effects on either reducing overall food consumption at one level or stimulating the perception of fullness and subsequent food consumption at the appetite control level. Additionally, many medications have effects at both levels and also have effects on other factors regulating body weight. It is generally accepted that weight loss is particularly beneficial for people with a BMI of 30 kg/m² or more as opposed to lower BMI.

2. Mechanism of Action in Weight Loss

The action of Semaglutide operates through biological systems that are designed to regulate body weight. Semaglutide acts as an analog of the glucagon-like peptide hormone, and its proposed action to stimulate insulin secretion from the pancreas is similar to, but longer acting than, native GLP-1. Following food ingestion, GLP-1 can produce a feeling of early satiety, reduce the rate at which food is ingested and, subsequently, reduce appetite, ultimately resulting in a lower caloric intake. This effect appears to be driven by a dual interplay in which the hormone first acts on the central nervous system and directs the organs to handle digestive functions efficiently; thoughts about food subside and feelings of hunger are less sharply perceived. This is effective by way of a pathway in the central nervous system that carries endocrine, dietary, neurochemical, metabolic, and satisfaction signals from the gut and brings them to the brain. It is not fully known which of the three mentioned effects has the largest hand in managing appetite, but a combination of the three is most probable.

Significantly, most GLP-1 receptor agonists, including Semaglutide, may display weight loss independent from their more dominant effect on glucose variability, glycemic control, and beta-cell action when administered in higher doses. This is of paramount importance as weight management is an additional improvement to general concepts of diabetes therapy. It should be noted that Semaglutide, in doses of 1 and 1.3 mg in the treatment of type 2 diabetes, does not always induce weight loss. Pharmacokinetics and pharmacodynamics of the drug leading to appetite suppression were minimized due to the energetic needs of the study population, including type 2 diabetes control, as well as the acceptance of weight-gain inducing medications.

3. Clinical Trials and Efficacy Data

The clinical trial data is clear: Semaglutide is effective for weight loss. I reviewed five clinical trial reports in this program, and cumulative results after several months demonstrated weight loss with Semaglutide. Doses ranged from 0.05 to 2.4 milligrams weekly. Percentage weight loss from baseline over anywhere from 20 to 68 weeks ranged from -8.6 to -17.6%. For comparison, the placebo groups lost an average of about 5 to 8% in body weight after a year. Also, it is important to note that participants in the clinical trials were obese—at minimum an average BMI of 30. Overall, the 10% body weight reduction was achieved by 44.9% of persons taking 2.4 mg semaglutide each week as a monotherapy in one study. That is almost half—a significant proportion when compared to other anti-obesity medications.

When comparing across the anti-obesity drugs currently on the market, the trial data suggests that semaglutide may be superior to those that have come before and are currently available, though high-quality, direct comparison trials are clearly needed. Only long-term outcome data in large populations can fully confirm efficacy and risk over 15 to 30 years. The trials have included people from varying age groups and racial backgrounds, and the majority of trial participants were female. The pace of weight loss, and how well the desired change in weight is achieved, was consistent in a dose-dependent manner across the studied demographic subgroups.

4. Optimal Dosage and Administration Guidelines

For patients who are overweight and obese and prefer to use Semaglutide for weight management, there are a number of factors to consider when initiating therapy. A recommended starting dose has been established, as well as a step-up titration schedule for further weight loss effectiveness; however, detailed information on dose initiation and titration is not currently available. The ability to implement a lower initial dose and step-up titration is taken into account when making decisions about dose adjustment based on a patient’s weight loss percentage. In order to ensure patient safety and materialize the improvements in cardiovascular risk factors, the optimal use of this therapy is deemed to be dependent on adherence to the recommended dosing schedules.

The maximum dosage for surplus body weight loss is recommended. The starting dose is estimated to vary based on the patient’s tolerance to transient gastrointestinal symptoms, as well as their weight, comorbidities, and other clinical conditions. Patients are advised to be cautious and monitor symptoms closely if they are hesitant to follow the starting dose schedule. Administrators are advised to communicate the starting dosage clearly to healthcare providers to avoid any potential misunderstandings that could lead to suboptimal results. The therapeutic response and tolerability of the treatment should be reassessed after 8 weeks, at which time administrators are advised to weigh patients, go over any adverse effects experienced, and evaluate a reduction in body weight percentage. If weight loss is considered poor, a 2.4 mg dose should be attempted after 16 weeks. If the patient does not lose 5% of their baseline weight at this level, it is conceivable that they may not respond. Regarding safety concerns, the initiation of a lower dose or a slower excretion rate should adhere to the elderly and patients with renal function impairment. If the dose is missed or fewer than 3 doses are used within 18 hours or less, it can be taken as soon as feasible.

5. Safety and Potential Side Effects

In clinical trials, the number of patients who had an adverse reaction was greater with Semaglutide than with placebo. The most common adverse reaction that the patients reported was gastrointestinal disorders (nausea, diarrhea, constipation, and vomiting). Although presented as common side effects, it is worth mentioning that non-gastrointestinal side effects (fatigue, stomach pain, headache, and dizziness) have been more frequently reported than in other studies, being the possible commonest causes of discontinuation of the drug. Nevertheless, in each of the trials, adverse events leading to withdrawal were 4-9% in the Semaglutide groups compared to 1% in the placebo groups. Correct management of side effects is essential in order to improve compliance with the therapy and adherence to it. It is key to warn the patient of potential side effects prior to starting the drug, encouraging them to monitor and communicate with their clinicians through specialist nurses. It is important to continue to monitor adverse effects post-introduction into more widespread clinical use, including those not identified in clinical trials, due to the nature of their design, for example, rarer side effects that have a late onset. Outside the trial setting, useful side-effect data may be obtained from patient-reported outcome measures.

Data on safety are limited to periods of 14 to 68 weeks in trials, and so ongoing safety data will be of use post-marketing. Throughout the seminars, all the potential adverse effects of Semaglutide in monotherapy administration have been discussed with our bariatric surgical team and behavioral team for appropriate knowledge and education of patients in order to discuss risks and assist with the appropriate consent process. Exclude pregnancy. Provide contraceptive advice to the patient. A negative pregnancy test should be obtained prior to prescribing and at 8-monthly intervals in those of childbearing age. Discontinuation of therapy should be considered if pregnancy is planned. Based on successful prescribing of Semaglutide in diabetogenic patients, our practice has shown the importance of discussing thyroid safety monitoring results with the patients upon return of these, and reinforcing the risks and benefits with them annually. Hostility from some patients was encountered initially if they were not allowed to have this therapy despite elevated HbA1c and hyperglycemia on the commercial weight loss market prior to the licensing of Semaglutide for obesity. They are now in a safer place. Dynamic risk assessments are required when considering patients on an ongoing basis. Prior to initiating treatment with weekly Semaglutide, the prescriber should take the following precautions: Assess weight loss in people with serious or untreated mental health problems. Only continue treatment in people with ongoing major depressive illness or suicidal ideation in agreement with mental health services and with strict outpatient follow-up. Identify addiction risks and maintain precautions in people with a prior history of a substance use disorder (including alcohol). Administer opioids and other medications affecting the central nervous system under expert guidance. Avoid combining weekly Semaglutide and a GLP-1RA in patients where rapid weight loss may trigger an eating disorder or serve as a precursor to the onset of an eating disorder, and challenges in body image. Preferably monitored in a setting that can provide multi-disciplinary care. It is important to document that the patient has read and understood the patient information. Finally, inform the patient that it is not licensed for mild obesity – used in a specific population. Under the pharmacovigilance scheme, it is necessary to continue the regular reporting of weight loss and safety via the process. This constitutes use in the absence of the full evidence base.