Obesity is a widespread and complex health issue with significant health and economic consequences. Multiple weight loss interventions have been developed during the past decades. Semaglutide, a glucagon-like peptide-1 receptor agonist, has emerged as a promising treatment option. This article delves into the effectiveness of semaglutide for weight loss, examining clinical trial data, real-world evidence, and practical considerations for individuals considering this medication.
Understanding Semaglutide
Semaglutide is a medication initially approved to treat type 2 diabetes. It functions as a glucagon-like peptide-1 (GLP-1) receptor agonist. Subcutaneous injection doses of 0.25, 0.5, and 1 mg are administered once weekly, and oral doses of 3, 7, and 14 mg are administered once daily. In June 2021, the FDA approved subcutaneous semaglutide for long-term weight management, with higher doses of 1.7 and 2.4 mg once weekly. Semaglutide Treatment Effect in People With Obesity (STEP) trials have demonstrated the efficacy of semaglutide for the treatment of obesity.
Clinical Trial Evidence: The STEP Trials
The Semaglutide Treatment Effect in People With Obesity (STEP) trials have shown the efficacy of semaglutide for the treatment of obesity. In large RCTs, patients receiving semaglutide, 2.4 mg, lost a mean of 6% of their weight by week 12 and 12% of their weight by week 28. These trials demonstrated that participants experienced significant reductions in body weight, often exceeding 10 to 15% of their starting weight. The magnitude of weight loss achieved with semaglutide was unprecedented among pharmacologic interventions for obesity, making it a game-changer in the field of obesity management.
In a 68- and 72-week clinical trial studying Wegovy (2.4 mg) and Zepbound (15 mg) in patients without diabetes and with BMI ≥30, or BMI ≥27 with a weight-related condition, the average weight loss was 15% and 20%, when paired with diet and exercise changes (compared to 2.4% and 3.1%, respectively, with diet and exercise alone).
Real-World Effectiveness: A Retrospective Study
To assess the effectiveness of semaglutide at the doses used to treat obesity (ie, 1.7 and 2.4 mg), a retrospective review of the electronic medical records (EMRs) of patients in the Mayo Clinic Health System using semaglutide between January 1, 2021, and March 15, 2022 was performed.
Read also: Transformations with Ozempic
The study included patients who had at least a 3-month follow-up documented in the EMR with a BMI of 27 or more who were prescribed weekly semaglutide subcutaneous injections of 0.25, 0.5, 1, 1.7, and 2.4 mg with the primary goal of weight loss. Patients with a history of bariatric procedures (ie, surgical or endoscopic), taking other FDA-approved AOMs, or with an active malignant neoplasm or pregnancy were excluded. Owing to high insurance denials and the national shortage of semaglutide, those patients were subsequently excluded from the analysis.
Key Findings
A total of 175 patients were included in the final cohort for analysis. The study revealed that patients lost approximately 6.7 kg at 3 months and 12.3 kg at 6 months, equivalent to 5.9% of weight lost at 3 months and 10.9% of weight lost at 6 months. These results suggest the effectiveness of semaglutide for patients aiming to lose weight.
Of the 102 patients who were followed up at 6 months, 89 (87.3%) achieved weight loss of 5% or more, 56 (54.9%) achieved weight loss of 10% or more, 24 (23.5%) achieved weight loss of 15% or more, and 8 (7.8%) achieved weight loss of 20% or more.
Comparison with Other Weight Loss Medications
Considering the scarcity of AOMs, choosing the most suitable and individualized therapy is important. In a 2021 systematic literature review, it was shown that 14% to 58.6% of patients achieved weight loss of 5% or more within 3 to 6 months when using orlistat, phentermine-topiramate, naltrexone-bupropion, phentermine, and liraglutide. However, in the retrospective study, 53.7% of patients at 3 months and 87.3% at 6 months had at least 5% weight loss.
A network meta-analysis comparing the weight loss outcomes of different glucagon-like peptide-1 receptor agonists demonstrated the following weight loss trends, from highest to lowest weight loss achieved: subcutaneous semaglutide, 2.4 mg weekly, −9.9 kg; subcutaneous liraglutide, more than 1.8 mg daily, −4.5 kg; subcutaneous semaglutide, less than 2.4 mg weekly, −4.3 kg; oral semaglutide (3, 7, and 14 mg) daily, −2.7 kg; subcutaneous liraglutide, 1.8 mg or less daily, −2.7 kg.
Read also: Comprehensive guide: Tirzepatide and Semaglutide for weight management
Factors Influencing Semaglutide Effectiveness
Several factors can influence the effectiveness of semaglutide for weight loss. These include:
Dosage
At 3 months, patients who received the highest doses (1.7 and 2.4 mg) achieved a mean weight loss of 6.9%, compared with a mean weight loss of 5.1% for patients receiving lower doses (0.25, 0.5, and 1 mg).
Presence of Type 2 Diabetes
Patients with type 2 diabetes had a lower mean percentage weight loss compared with those without type 2 diabetes at 3 months (3.9% vs 6.3%) and at 6 months (7.2% vs 11.8%). This difference was also seen in previous studies with semaglutide and in other studies in which patients with type 2 diabetes had a weight loss inferior to that of matched patients without type 2 diabetes. A possible explanation could be a greater decrease in energy expenditure among patients with type 2 diabetes compared with those without type 2 diabetes.
Lifestyle Interventions
It's important to note that semaglutide is not a quick fix for weight loss, and it should be used as part of a comprehensive weight management plan that includes lifestyle changes, such as a healthy diet and regular physical activity. A comprehensive and inclusive systematic review suggests that behavioural weight loss interventions result in improvements in a number of mental health outcomes, including body image concerns, depression, mental health-related quality of life, self-efficacy, exercise self-efficacy, and diet self-efficacy.
Duration of Treatment
When using semaglutide injections for weight loss, it is generally recommended to continue the treatment for an extended period, as maintaining weight loss can be challenging. The duration of semaglutide treatment for weight loss can vary, but many healthcare providers recommend a minimum of 12 to 24 months for chronic weight management.
Read also: Semaglutide Without Diet Changes
Individuals can expect to lose approximately 15 to 17% of their baseline body weight on average after one year of treatment with the 2.4mg once-weekly semaglutide injection when combined with lifestyle interventions. For most people, the weight loss achieved with semaglutide starts to plateau around 9 to 12 months of treatment if the individual adheres to the medication and lifestyle recommendations.
Individual Response
How long you take a weight-loss drug depends on whether your body is responding to it. If you’ve lost adequate weight and aren’t struggling with side effects, your prescribing provider may suggest that you take the drug long-term. Since the medications often help by decreasing your appetite, they can be beneficial in both losing weight and maintaining weight loss. If you haven’t lost at least 5% of your body weight after taking the full dose of a drug for three to six months, your provider may discontinue or change your weight loss treatment.
Potential Side Effects and Considerations
As you just read, all medications come with the potential for side effects. Some people don’t experience any side effects whereas others might find them to be overwhelming. If you’re finding your medication is more bothersome than you can bear, especially if it is interfering with your daily life and activities, let your health care team know. Your prescribing provider might be able to adjust the medication dosage to reduce your symptoms.
In placebo-controlled trials, the most common adverse reactions reported in ≥5% of patients treated with Ozempic® are nausea, vomiting, diarrhea, abdominal pain, and constipation.
In the retrospective study, adverse effects were reported in approximately 50% of the cohort during follow-up. Gastrointestinal symptoms were the most reported adverse effects. Nausea and vomiting were the most encountered adverse events (64 patients [36.6%]), followed by diarrhea (15 patients [8.6%]) and fatigue (11 patients [6.3%]).
Other potential side effects of Wegovy® include:
- Possible thyroid tumors, including cancer. Tell your healthcare provider if you get a lump or swelling in your neck, hoarseness, trouble swallowing, or shortness of breath. These may be symptoms of thyroid cancer. In studies with rodents, Wegovy® and medicines that work like Wegovy® caused thyroid tumors, including thyroid cancer.
- Inflammation of your pancreas (pancreatitis). Stop using Wegovy® and call your healthcare provider right away if you have severe pain in your stomach area (abdomen) that will not go away, with or without nausea or vomiting.
- Gallbladder problems. Wegovy® may cause gallbladder problems, including gallstones. Some gallstones may need surgery.
- Increased risk of low blood sugar (hypoglycemia), especially those who also take medicines for diabetes such as insulin or sulfonylureas. This can be a serious side effect. Talk to your healthcare provider about how to recognize and treat low blood sugar and check your blood sugar before you start and while you take Wegovy®.
- Dehydration leading to kidney problems. Diarrhea, nausea, and vomiting may cause a loss of fluids (dehydration), which may cause kidney problems. It is important for you to drink fluids to help reduce your chance of dehydration.
- Severe stomach problems. Stomach problems, sometimes severe, have been reported in people who use Wegovy®.
- Increased heart rate. Wegovy® can increase your heart rate while you are at rest.
- Depression or thoughts of suicide. You should pay attention to any mental changes, especially sudden changes in your mood, behaviors, thoughts, or feelings.
- Food or liquid getting into the lungs during surgery or other procedures that use anesthesia or deep sleepiness (deep sedation). Wegovy® may increase the chance of food getting into your lungs during surgery or other procedures.
Additional Considerations
- Many weight-loss medications require that you inject yourself with the medication. You may face challenges such as needle phobia or have difficulty with proper injection techniques. Injection site reactions such as redness, swelling or itching can also be a deterrent. While these reactions are usually mild and transient, they can still be uncomfortable. Contact your provider to ensure you have thorough training on proper injection techniques to ensure a confident, accurate and comfortable self-injection. A different type of needle also may help reduce discomfort during injections.
- Weight-loss medications can be costly, and they’re not always paid for by insurance or covered long-term. You might consider exploring financial assistance programs as some pharmaceutical companies offer patient assistance programs or co-pay assistance programs to help reduce the cost of the medications.
- It may be necessary to stop the medication if you have a change in health conditions. That’s why it’s important to have ongoing conversations with your health care team to assess your medication. Keep in mind that a lifestyle intervention program, like the Mayo Clinic Diet, can continue to support you on your weight-loss journey regardless of whether you’re taking a weight-loss medication.
- Wegovy® may harm your unborn baby.
- Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Wegovy® may affect the way some medicines work and some medicines may affect the way Wegovy® works. Tell your healthcare provider if you are taking other medicines to treat diabetes, including sulfonylureas or insulin.
The Importance of a Holistic Approach
Semaglutide can be a valuable tool for weight loss, but it is most effective when combined with a holistic approach that includes lifestyle modifications, nutritional guidance, and ongoing support from healthcare professionals.
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