Obesity: GLP-1 therapies

Finally, the microbiome has a variety of mechanisms through which it affects obesity, and pre/probiotic therapies could be a helpful addition to a weight loss regimen 58,59. In addition to its effect on body weight, a variety of health benefits have been ascribed to it. Regular physical activity is also recommended as a component of weight loss programs not only for energy expenditure, but for cardiometabolic health as well . In this review, we examine the health risks of obesity and the overall magnitude of the problem. Obesity as defined by The Obesity Society (TOS) is a multi-factorial chronic disease that results from excess fat accumulation that presents a risk to health . In contrast to the already-approved Wegovy, the voucher for Lilly’s orforglipron represents a novel drug approval. We look forward to working with the FDA to bring this fast-tracked option to the obesity community,” said Anna Windle, Senior Vice President, Clinical Development, Medical and Regulatory Affairs, Novo Nordisk. Lilly said earlier this year that they have plans to submit for approval of the drug by the end of the year. Since Wegovy is already FDA-approved, Novo Nordisk announced on November 26th that they have filed their voucher for approval of a higher-dose version at 7.2mg. This article is part of our series on the FDA’s National Priority Voucher program, exploring the therapies selected, their potential impact, safety considerations, and what accelerated review could mean for patients in the US and globally. This initial dose helps your body adjust to the medication and reduces the risk of side effects. This injectable medication is a novel treatment option for people struggling with obesity or overweight issues. Levels of circulating semaglutide determine reductions in HbA1c and body weight in people with type 2 diabetes. “If approved, semaglutide 7.2 mg would bring patients and healthcare professionals a new option for greater weight loss potential, further underlining the efficacy that the semaglutide molecule can bring. Having patients track intake and physical activity has been shown to be helpful. Working with a dietician may help patients alter their food choices, but discussion of decreasing caloric intake is also helpful. Part of the GLP-1 action is to activate metabolism of brown fat and adipose redistribution with decreased visceral fat and relative increase in lower-body subcutaneous fat deposition.8 GIP is also an incretin hormone involved in energy and nutrient metabolism through cell surface receptor signaling in the brain and adipose tissue.2 Fortunately, through research we have a better understanding and way to approach treating obesity. If it were simple to overcome obesity, we would have already done it. GPL-1 therapies are generally long-term treatments, meaning for 6 months or longer. However such risk in humans is still under investigation. GPL-1 therapies are efficacious for reducing weight. They should only be prescribed by a medical practitioner, after taking into account individual health history and clinical indications. Lower blood sugar helps control type 2 diabetes. GLP-1 agonists mimic the way a hormone called glucagon-like peptide 1 works in the body. Tirzepatide (Mounjaro) is a similar kind of medicine called a dual-acting GLP-1/GIP agonist. Incretin-based medications and other anti-obesity medicines target hunger, therefore fostering both weight loss and weight loss maintenance. The landmark GLP-1 drug trial for semaglutide, STEP 1 (semaglutide treatment effect in people with obesity), demonstrates a significant loss of total lean body mass , which has been further corroborated by other investigators . GLP-1 medications have revolutionized weight loss and can reduce body weight in obese patients by between 15% and 25% on average after about 1 year. Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. This medicine is also used to lower the risk of heart attack, stroke, or death in patients with type 2 diabetes, obesity, and heart or blood vessel disease.

GLP-1 Receptor Agonists and Weight Loss

When given in doses between 130 and 250 mg/kg, this herb reduced pain by 50-80% without causing tolerance. Daily administration of morroniside for a week showed consistent pain-relieving effects without developing tolerance. Morroniside, another GLP-1 RA, reduced pain responses in a dose-dependent manner in rats experiencing neuropathic pain. Table 1. Summary of the CVS outcome trials, their primary endpoints, and study populations.

Table 1. Summary of the CVS outcome trials, their primary endpoints, and study populations.

Wegovy and Zepbound are FDA-approved for patients with a BMI of 30 or greater; or a BMI of 27 or more if they have a weight-related complication. Noom doesn’t “necessarily frown” upon people starting and stopping its microdosing program, including losing weight for a wedding or a vacation, Egler says. Still, side effects can occur at any dosage, so it depends on each person’s response to the medication, McGowan adds. Gastrointestinal side effects tend to be less at a lower dose so that’s possible, says Levy who has done consulting work for Novo Nordisk. Emerging data have established that GLP-1 agonist administration has not increased the risk of malignancy outside of the thyroid gland and may in fact reduce the risk of malignancy with potential for preventive applications 203,204. All studies are in agreement that the greatest risk if any does occur in the initial months or year of therapy 200,201,202,203,204. Two trials have supported an increase in the risk of all types of thyroid carcinoma 200,201. The exact risk change with other histological subtypes of thyroid carcinoma is yet to be fully established. Parks and Rosebrough first expressed concerns regarding human safety with liraglutide as early rodent trials demonstrated an increased risk of medullary thyroid carcinoma . If you prefer a needle-free GLP-1 medication, the Wegovy pill can be a good choice. But Wegovy also comes in pill form, providing more options for treatment. GIP is thought to work together with GLP-1 in some ways for additive effects. They may suggest adjustments to one or more of your medications. So it could delay the absorption of oral medications. It’s likely your healthcare team will suggest alternatives if this dosage causes too many side effects. But keep in mind that 5 mg per week is considered the lowest effective dosage for weight loss. But it's not clear exactly how GLP-1 agonists lead to weight loss. When blood sugar starts to rise after a person eats, these medicines cause the body to make more insulin. Other GLP-1 agonists appear to be somewhat less effective for weight loss. In some cases, they may be able to raise it or switch you to a different medication. In this case, your prescriber may have you start with a lower Zepbound dose and slowly work your way up. But each medication’s dosage schedule looks a bit different. The FDA has approved Wegovy (semaglutide) as a treatment option for decreasing the risk of cardiovascular events in overweight or obese individuals, following the promising results of these trials . As mentioned by Lingvay et al., semaglutide has shown promise as a treatment option for non-diabetics with established atherosclerotic disease by reducing their risk of MACE by 20% despite having varying HBA1c baselines . More data and long-term studies are needed to determine the side effect profile and the long-term effects of these medications on the human body . The effects of exogenous GLP-1 after administration to T2DM patients show improved insulin sensitivity, decreased glucagon concentration, slowed gastric emptying, increased satiety, decreased fatty acid concentration, lowered body weight, and overall decreased hemoglobin A1c (HBA1c) levels.

Since Zepbound and Wegovy work in similar ways, this combination could increase the risk of side effects.
Following these initial results, the SOUL trial was commenced to specifically study the efficacy of oral semaglutide on cardiovascular health and find if oral semaglutide can be more beneficial than placebo.
If a woman becomes pregnant while on a GLP-1 drug, it should be stopped immediately, and she should consult her treating physician or an obstetrician as soon as possible.
“The rates of obesity have steadily increased over the past few years with more individuals becoming candidates for this type of treatment,” Dr. Eliud Sifonte, a diabetes and metabolism endocrinologist affiliated with NYU Langone Health, told Flow Space.
Another form of semaglutide is available in a pill that's taken by mouth once a day.
“It really goes against what we're trying to do in the field of obesity and treat chronic illness,” Levy adds.
GLP-1 receptors have been found in both healthy and OA-affected cartilage cells in rat knees.
In January 2024, the FDA announced it was evaluating reports of hair loss and suicidal thoughts in patients taking Ozempic, Mounjaro or Wegovy.

If you miss a dose, and the next scheduled dose is less than 2 days away, skip the missed dose and go back to your regular dosing schedule. If you miss a dose of Wegovy®, and the next scheduled dose is more than 2 days away, use it as soon as possible. If you miss a dose for more than 5 days, skip the missed dose and go back to your regular dosing schedule. If you miss a dose of Ozempic®, use it as soon as possible within 5 days after your missed dose. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. There have also been ongoing shortages of some of the doses of the medications. It should be noted that the cost of future healthcare needed from consequences of obesity is likely to be more than that of the medication. Each of the three medications has coupons on the manufacturer website patients can apply for, however, if they have government insurance, they are exempt from qualifying. Once patients decide to start medication, they should be counseled on side effects and how to take the medication. Liraglutide is a multiple use pen that requires a new needle with each injection and patients dial the pen to their dose, semaglutide and tirzepatide are single use pens.15,16,17 Following the promising results of the REWIND trial, FDA approved Trulicity (Dulaglutide) in those with T2DM who either have cardiovascular disease or are at increased risk of the disease to be used preventively for reduction in MACE . A review by Helmstädter et al. in 2021 outlined these benefits, with liraglutide reducing death of heart-related disease events by 13% as per the LEADER trials and semaglutide demonstrating a 26% reduction in MACE. A comprehensive meta-analysis conducted by Sattar et al. studying the effects of GLP-1 RAs on the heart showed a promising 12% reduction in mortality, with a 14% decrease in the risk of cardiovascular events and an 11% decrease in the rate of hospital admissions due to heart failure. It contains the active ingredient semaglutide, which is a glucagon-like peptide-1 (GLP-1) receptor agonist. In this case, compounded semaglutide may seem like a tempting alternative. Even so, compounded semaglutide products may not disappear completely. Your doctor will determine the appropriate dose based on your health profile and weight loss goals. FDA’s concerns with unapproved GLP-1 drugs used for weight loss. Every medicine for any disease has side effects, and there’s always a risk-to-benefit ratio to consider, Jastreboff added. The most common problems for patients taking blockbuster anti-obesity medications like Wegovy and Zepbound are gastrointestinal issues including nausea, diarrhea and constipation.

Which medication has been proven to reduce the risk of serious cardiovascular events in people with heart disease?

In this review, we explore the current medical therapies for obesity, including all major categories, individual mechanisms of action, pharmacokinetics and pharmacodynamics, adverse effects, risks, and absolute contraindications. This review investigates the various pharmacologic treatments for overweight and obesity in adults, especially glucagon-like peptide 1 (GLP-1) agonists. The right dose, along with proper administration, can help you effectively lose weight and maintain a healthy lifestyle. On average, people can expect to lose around 5-10% of their body weight within 6 months of using GLP-1. However, this should only be considered if you’ve been on the lower doses for a while and need further weight loss support.

Should you track your blood sugar with a continuous glucose monitor?

GLP-1 RAs have shown consistent results in managing blood glucose levels by lowering HbA1c with minimal hypoglycemic risk and increasing insulin production and synthesis. Although, in the last 10 years, the use of GLP-1 RAs, especially semaglutide and liraglutide, has increased, its clinical implications and how it affects metabolic parameters have yet to be fully consolidated. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been developed to manage type 2 diabetes mellitus. Ensuring quality requires regulated distribution and prescription by a qualified health care providers, strong oversight, patient education, and global cooperation to protect public health. Semaglutide subcutaneous route Side effects & dosage

Semaglutide subcutaneous route Side effects & dosage

Kessler says drugmakers should do more to inform patients about the risks of developing eating disorders, and gastroparesis – a chronic condition where gastric emptying slows down significantly. "From what I can tell, many people on these highly effective drugs are eating less than a thousand calories a day, some as low as 600 to 800, and that is a level of semi-starvation," says Kessler. Kessler worries about people taking the drugs going too far in the other direction – from overeating to malnutrition. He says if you're trying to lose weight, with or without drugs, protein is key, because it increases feelings of fullness. The side effects are one reason it's important to work with a physician who can monitor your progress and help you find the right drug at the right dose.

At this time, very little attention is being afforded to the discontinuation of GLP-1 drugs after weight loss has occurred, but this may change if serious consequences of prolonged exposure in young persons are documented.
Always consult a specialist for specific health diagnosis.
If you or your caregiver notice any of these side effects, tell your doctor right away.
GLP-1 receptor agonist drug development began in earnest in 2005 with the approval of exenatide, a synthetic form of a natural peptide hormone isolated from the saliva of the venomous lizard Gila monster .
Variations of Roux-en-Y gastric bypass limb lengths have shown potentially increased weight loss and metabolic benefit, but also, possible early and late significant complications 75,76,77.
Guidance regarding semaglutide-based medications from the Mississippi State Board of Medical Licensure.
Scientists are finding that the drugs may be useful to treat addiction and heart disease.
For instance, the SELECT trial demonstrated the cardiovascular benefit of the GLP-1 receptor agonist semaglutide beyond that of weight loss .

Talk with your healthcare team about these risks before trying it. Compounded medications are not tested for safety and effectiveness like FDA-approved products. It’s common to regain some of the weight you lost after stopping the medication. This helps you adjust to the medication and helps limit side effects. It can be tough to remember medications when you’re not taking them every day. All GLP-1 agonists can help with weight loss. It's also used to control blood sugar and can support weight loss. Since that first seven months, he's been on and off the drug again.

What Is GLP-1 Microdosing and Does It Lead to Weight Loss? Doctors Explain

First, there was a greater overall weight loss of 15% and therefore the weight loss plateau was delayed to around 68 weeks. Similarly, the subcutaneously once weekly formulation of the GLP-1 receptor agonist semaglutide showed equally promising results for weight maintenance . SELECT also showed better cardiovascular outcomes in persons with obesity and without diabetes who had previously undergone coronary artery bypass graft surgery .

Doctors then gradually increase it so a patient’s body can get used to the drug, working up to a maximum dose of 2.4 milligrams a week, according to Novo Nordisk, the pharmaceutical company that makes it.
However, the only truly long-term strategy that has been the most successful for long-term weight loss is surgical weight loss.
"Our study found that patients using GLP-1 receptor agonists are more likely to have inadequate bowel preparation during colonoscopy, even when we account for other comorbidities, such as diabetes, heart failure, inflammatory bowel disease, constipation and use of opioid medications."
However, tirzepatide is a novel dual agonist drug that activates GLP-1 receptors, as well as the GIP receptor.
Wait at least 30 minutes before eating, drinking anything else, or taking other medications.
But you may be more likely to experience side effects.
Admittedly, the lesser potency of these drugs in the initial weight loss phase often overshadows their potential for usage for weight loss maintenance purposes.

This medicine may cause severe stomach and bowel problems. If you think you have become pregnant while using this medicine, tell your doctor right away. Do not put this medicine back in the refrigerator if it has been stored at room temperature. Store your medicine pen in its original carton in the refrigerator. If you miss a dose for more than 4 days, skip the missed dose and go back to your regular dosing schedule. This model of body fat regulation was widely adopted in the 1990s with the discovery of leptin 3,4. He suggested that adipose tissue may produce a signal that may be sensed by the brain to target a “level of body fatness”. The concept that body fat storage may be regulated was first proposed by Kennedy et al. through the concept of a “set point” . Ultimately, understanding the existing forces that occur in a weight-reduced state may help to understand what may drive weight regain 224,225. Additionally, there are those who are attempting to prevent weight regain after already achieving a weight-reduced state. Definitions of weight regain may vary, namely the duration and how much is considered significant. Common adverse effects of GLP-1 agonists and approaches to minimizing these consequences. But the risk of side effects also goes up with higher doses. In clinical trials, the 15 mg dose of Zepbound led to greater weight loss than the 5 mg and 10 mg doses. They’ll check your body weight and ask you about side effects. Despite the overall efficacy of the incretin-based treatments for weight loss, there is a lack of long-term controlled studies beyond about 4 years available 221,222. As with all new medications or those whose use increases due to expanded indication, ongoing monitoring and close surveillance by both patients and clinicians continue to be necessary. Secondarily medically induced weight loss, particularly when totaling in excess of 5% of total body weight has demonstrated effectiveness in improving fertility . The question of whether the ratio between fat mass and lean body mass is disrupted or maintained during weight loss with GLP-1 agonists is still unresolved 183,184. The rapid weight loss can be visualized in many areas of the body and one of these manifestations known as “Ozempic face” occurs when fat pads in the face are rapidly depleted 177,178. Weight loss may not be immediate, but with consistent use of the medication and a healthy lifestyle, long-term results are achievable. GLP-1 is highly effective for weight loss when used as part of a comprehensive weight management plan that includes diet and exercise. The doses of GLP-1 vary depending on the stage of treatment and individual needs. Additionally, these GLP-1 RAs have been explored as an effective means of weight loss, with the STEP clinical trials showing a mean of 5% weight loss at the end of 68 weeks of treatment. This narrative review explores the metabolic effects of GLP-1 RAs in weight management, blood glucose, cardiovascular health, lipid profiles, and blood pressure. While GLP-1 therapies represent the first efficacious treatment option for adults with obesity, the WHO guideline emphasizes that medicines alone will not solve the problem. The weight loss it produces is “profound” and might be a good fit for people with a very high BMI, Levy added. Individual clinical trials also suggest that Zepbound may result in greater weight loss than Wegovy injections and pills. Results showed greater weight loss with Zepbound compared with Wegovy (20% vs. 14%) at 72 weeks (16.5 months). Wait at least 30 minutes before eating, drinking anything else, or taking other medications. Wegovy belongs to a class of medications called glucagon-like peptide-1 (GLP-1) receptor agonists. Such a rapid increase in usage led to multiple drug shortages beginning in 2022 which continued through late 2024 . The newest incretin-based medication is a combined GLP-1 receptor and glucose-dependent insulinotropic polypeptide (GIP) dual agonist known as tirzepatide. In this placebo-controlled trial, subjects were over the age of 45 years, had a BMI of 27 or above, and established cardiovascular disease. However, challenges remain in such multi-agonist receptor treatments, and the focus remains predominantly on energy intake . However, even during active weight loss, metabolic adaptation seems to be set into motion, and in fact may be triggered by achieving 11% of total body weight loss 236,237. For those with untreated obesity and seeking active weight loss, decreasing hunger and achieving caloric restriction is seemingly the primary process that needs to occur. The conceptual framework for weight regain and weight loss maintenance is based on the theory that the human body acts to defend a particular body mass, via the hypothetical “settling point” of weight 226,227,228. This can be attributed to the persistent effects of metabolic adaptation, the phenomena seen in weight regulation that may cause weight regain and potentially a weight loss plateau . GLP-1 Agonists for Weight Loss: Pharmacology and Clinical Implications

GLP-1 Agonists for Weight Loss: Pharmacology and Clinical Implications

According to the American Diabetes Association, the first-line glycemic control therapy focuses on comorbidities, lifestyle modification, and medications such as metformin and combination therapy with GLP-1 RAs and sodium-glucose cotransporter-2 (SGLT-2) inhibitors . With the present data available, it is well established that GLP-1 RAs are effective medications for lowering blood glucose levels and managing T2DM. This narrative review aims to explore the role of GLP-1 RAs in weight management and cardiovascular health, and how they affect metabolic parameters such as blood glucose, lipid profiles, and blood pressure. In conjunction with all the effects, GLP-1 RAs have been found to lower weight and aid in weight management. In this narrative review, we have explored the varying effects of these agents on essential metabolic parameters such as blood glucose, cardiovascular health, weight management, blood pressure, and lipid profile in both diabetic and non-diabetic patients. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), especially semaglutide (famously known as Ozempic® or Wegovy®), have become very popular in recent years for weight loss, even though their initial indication is for the management of the patient with diabetes mellitus. Levy calls the notion of people buying unapproved weight-loss drugs “scary.” Links to NCBI Databases

When starting GLP-1/GIP for weight loss, it’s important to follow the prescribed GLP-1/GIP dosage carefully. GLP-1/GIP is primarily used for type 2 diabetes, but its weight-loss benefits have been proven in clinical trials. It is designed to work by improving insulin sensitivity and suppressing appetite, making it an effective option for people with obesity. Studies suggest that GLP-1 drugs are not a direct cause of depressive symptoms in weight loss . While there is optimism that continuing use of GLP-1 treatments will preserve weight loss, most other anti-obesity strategies, including surgical interventions, generally have weight recidivism . Early case reports called into question appropriate fasting times for pre-procedural and operative fasting due to retained gastric contents and risk of aspiration in patients taking GLP-1 medications and compounds 213,214. It is unclear whether those without type 2 diabetes using GLP-1 for weight loss are at the same risk 197,198. Zepbound (tirzepatide) is one of these medications. Weight-loss medications are all over the news. However, the drugs did improve unspecified markers for Alzheimer’s, which signals it could potentially be helpful for prevention—pending further study. However, Novo Nordisk, Ozempic’s manufacturer, released results from two clinical trials in November 2025 that showed that taking an oral GLP-1 didn’t slow disease progression among people with Alzheimer’s compared to those who took a placebo. Whether the drugs can be used to prevent or treat dementia is also being studied, with mixed results. GLP-1 is a revolutionary medication that has shown great promise in helping individuals lose weight. It is also used to treat moderate to severe obstructive sleep apnea (OSA) in patients with obesity. If you notice any other effects, check with your healthcare professional. Other side effects not listed may also occur in some patients. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. No, there aren’t any recommended Zepbound dosage adjustments for people with certain health conditions, such as kidney or liver disease. This low dosage helps limit digestive side effects, such as nausea and diarrhea, while your body adjusts to the medication. With some medications, such as Zepbound, it can take a few weeks to reach the maintenance (steady) dose. Whyte says the significant reduction in alcohol use can lead to weight loss and overall improved health outcomes. Scientists are finding that the drugs may be useful to treat addiction and heart disease. That’s a wider pool of people than those who normally qualify for a GLP-1 prescription. Noom allows patients with a BMI of 25 or higher to take part in its microdosing program. “It really goes against what we're trying to do in the field of obesity and treat chronic illness,” Levy adds. In a TODAY segment that aired on Nov. 21, 2025, Egler added that whatever motivates somebody to change their life is worth pursuing. Noom’s microdose program starts at $119 for the first three weeks, and costs $199 per month after that, without insurance. But what should you do if you need to switch from compounded semaglutide to Ozempic or Wegovy? They can tell you about their ingredient sources, what’s in your medication, quality control processes, and more. In most cases, your next step would be switching from compounded semaglutide to an FDA-approved product. As mentioned, compounded copies of semaglutide injections have been largely phased out. Working with an experienced, reputable pharmacy can help lower the risk of these potential issues. Noom's microdosing program also offers liraglutide, Egler says, an older generation GLP-1 drug that’s now available in generic form and comes in a pen. Still, pharmacies can distribute compounded versions of GLP-1s if the medication is personalized for the patient’s needs, according to the Center for Medicine in the Public Interest. Before this past spring, many compounding pharmacies were selling copycat versions of GLP-1s, which the FDA permits if a drug is in shortage. Microdosing is considered off-label use, or prescribing an approved drug for an unapproved use, which doctors are allowed to do if they deem it medically appropriate. This is difficult because weight loss activates central and peripheral compensatory mechanisms that counter weight loss and favor weight gain.4 When lifestyle intervention is the sole treatment, weight is typically regained even with continued compliance.6 Treatment requires a comprehensive approach that includes lifestyle interventions, pharmacotherapy and in some instances, bariatric surgery. Many of the effects of obesity can be halted, reversed, and prevented by losing weight. Patients with obesity are at higher risk of mental health disorders, physical and sexual dysfunction.4 Clinical research and studies uniformly demonstrate their ability to contribute to notable weight loss, improve lipid profiles, lower blood pressure, and reduce cardiovascular risk.

Following the recommended Zepbound dosage schedule helps limit common side effects, such as nausea and diarrhea.
They were originally used for managing type 2 diabetes, but are now also approved for treating obesity and weight loss.
Research study on whether semaglutide works in people with non-alcoholic steatohepatitis (NASH) (ESSENCE).
"And that inflammatory state results in organ damage that leads to cardiometabolic disease, kidney disease, diabetes, certain forms of cancer, and potentially certain neurodegenerative changes," says Kessler.
This gives your body time to adjust to Zepbound and find the right dose for you.
When people stop treatment, "rapid weight regain" can happen, a 2026 review of studies found.
He says if you're trying to lose weight, with or without drugs, protein is key, because it increases feelings of fullness.

A BMI (in kg/m2) in the range of 18.5–24.9 is considered normal, 25–29.9 is overweight, and ≥30 is considered obese. Obesity is traditionally defined as an excess of body fat, and is classically categorized in clinical practice in terms of body mass index (BMI). This is also why developing pharmacologic treatments is challenging without clear targets. No, while GLP-1 therapies are used for the treatment of people with obesity, they should not replace other means of weight control. Based on current WHO recommendations, GLP-1 medicines may be used as a long-term treatment option for adults with obesity (body mass index ≥30). They were originally used for managing type 2 diabetes, but are now also approved for treating obesity and weight loss. If you’re ready to start your weight loss journey with GLP-1, consult your healthcare provider to determine the best GLP-1 dose for your needs. Possible complications of the gastric bypass include bowel obstruction and malabsorption, while possible complications of the sleeve gastrectomy include venous thromboembolism and gastroesophageal reflux disease 78,79. The intragastric balloon is an anti-obesity intervention in which a silicone balloon is endoscopically deployed and filled with saline and inflated for 6 months. For instance, the Contrave Obesity Research studies (COR-I, COR II, COR-BMOD, and COR diabetes) were performed over a 56-week period 64,65. Patients are advised to consume a low-fat diet to combat the side effects of oily stool . The weight loss benefits of SGLT-2 inhibitors typically are less than those of GLP-1 agonists. These medicines work in the kidneys where they help take extra sugar out of the blood that then goes out of the body in urine. But the risk of low blood sugar typically only goes up when a person also is taking another medicine that's known to lower blood sugar. More common side effects often improve after taking the medicine for a while. Data were collected by comparing GLP-1 RAs, such as semaglutide, liraglutide, tripeptide, and exenatide, as well as comparing them to a baseline treatment group. The guideline emphasizes the importance of fair access to GLP-1 therapies and preparing health systems for use of these medicines. Beyond its health impacts, the global economic cost of obesity is predicted to reach US annually by 2030. Therefore, treating hyperphagia is the strategy for both weight loss and weight loss maintenance. In this setting, prevention of weight regain may be better-termed weight loss maintenance. It is worthwhile to point out that a weight loss plateau is often stated with the assumption that additional weight loss is desired, but difficult to achieve. The general trajectory of weight loss with initiation of GLP-1 therapy has been well-studied (Table 2) 218,219,220. Although GLP-1/GIP is a useful weight-loss aid, it’s important to comprehend certain important aspects regarding dose. Before altering your drug schedule, always get advice from your healthcare professional. GLP-1/GIP is typically given for long-term use, especially in cases of weight loss. This gives time for your body to become accustomed to the medication and experience its benefits without overwhelming your system.

Missed Dose

The amount of medicine that you take depends on the strength of the medicine. If your dose is different, do not change it unless your doctor tells you to do so. Use this medicine on the same day each week, at any time of the day, with or without meals. Never share medicine pens with others under any circumstances. It is acceptable to inject these in the same body area, but the shots should not be right next to each other. Liraglutide was the first GLP-1 approved for weight loss and was studied in the Satiety and Clinical Adiposity-Liraglutide Evidence (SCALE) trials.9 The initial SCALE study evaluated the efficacy of liraglutide 3mg once daily in individuals with BMI greater than 27kg/m2 with one or more comorbid conditions or BMI greater than 30kg/m2. These medications work by mimicking the natural GLP-1 which is an incretin peptide released from cells in the bowel.5 It enhances insulin secretion in the hyperglycemic state, inhibits glucagon secretion, delays gastric emptying, regulates food preference, and reduces food intake by increasing satiety thru central appetite suppression. Traditionally, weight loss centered around discussions of reduced caloric intake and increased physical activity.

Compounded semaglutide is a medication that’s custom-made for you by a compounding pharmacy.
While the benefits are undeniable, the blockbuster growth and use of GLP-1 drugs has also highlighted potential side effects.
During the approval process, the FDA also evaluated where and how these medications are made.
Avoid buying semaglutide that doesn’t require a prescription.
The metabolic efficacy of bariatric surgery in increasing gut production of GLP-1 to supraphysiologic levels postprandially is considered a major factor in early weight loss .
While there is optimism that continuing use of GLP-1 treatments will preserve weight loss, most other anti-obesity strategies, including surgical interventions, generally have weight recidivism .

As analyzed by the recent meta-analysis of these trials, there is a 32% prevalence of heart-related diseases in T2DM patients. Following these initial results, the SOUL trial was commenced to specifically study the efficacy of oral semaglutide on cardiovascular health and find if oral semaglutide can be more beneficial than placebo. These results showcase the ability of semaglutide to be a treatment option for cardiovascular benefit, notwithstanding the glycemic index. Various CVOT trials, such as the SELECT, SUSTAIN, and SOUL trials, have demonstrated varying effects on heart diseases over the years 13,39,46. Always follow your doctor’s guidance when adjusting your GLP-1 dose. The GLP-1 maintenance dose is often adjusted based on individual needs and response. However, if you need further improvement, your doctor might suggest increasing the dose to 2 mg per week. This medicine may cause dehydration which can lead to acute kidney injury. However, low blood sugar can occur when you use tirzepatide with other medicines, including insulin or sulfonylureas, that can lower blood sugar. The treatment appeared to counteract the abnormal expression of 591 genes in the spinal cord that had been altered by nerve damage, especially those involved in inflammation, including TNF-α and toll-like receptors. This means that GLP-1 could help treat osteoporosis and similar bone issues, particularly in people with T2DM. In osteoporosis, GLP-1 RAs such as exendin-4 can help by increasing osteocalcin levels, a protein essential for bone health. GLP-1 receptors have been found in both healthy and OA-affected cartilage cells in rat knees. So far, there have yet to be any direct studies in humans to show whether GLP-1-based treatments are effective for OA, pointing to a gap in current research. Common side effects are gastrointestinal related and include diarrhea, nausea, and stomach pain. But you may be more likely to experience side effects. If you find yourself needing to change injection days frequently, speak with your healthcare team. With the potential for delayed gastric emptying absorption of other medications should be considered.6 Most of the drug interactions are increased risk of hypoglycemia therefore education about symptoms is important. Given that the gastrointestinal side effects are transient, and patients continue to lose weight it is likely not the side effects causing the weight loss.8 The use of medications for weight loss needs to be an adjunct to diet and lifestyle changes to ensure the weight loss is sustainable. Semaglutide is indicated for weight loss in pediatric patients over the age of 12 with obesity. Up until recently, the medications used to treat obesity were not very effective and had many limiting side effects and contraindications. Because GLP-1 medications completely rewire hunger and fullness cues, there’s a concern about getting proper nutrition while taking them. The most commonly reported side effects of semaglutide include gastrointestinal issues, such as nausea, vomiting, diarrhea and constipation. Data analyzed by Epic Research showed an increase in use of these drugs by 40-fold between 2017 and 2021, estimating that six million Americans are now on either Ozempic or Mounjaro. After four weeks on the initial dose, your healthcare provider will suggest increasing your dose. This low dose helps your body become accustomed to GLP-1 without overwhelming it. For most patients, the starting dose is 0.25 mg once a week. These findings should allow clinicians to prescribe these valuable medications with greater confidence. Given that the increased risk appears to be an artifact of detection bias, these findings do not support implementing routine thyroid cancer screening for patients initiating GLP-1RA therapy. For most patients without a personal or family history of MTC or MEN2, the proven metabolic and cardiovascular benefits of GLP-1RAs appear to far outweigh what this study suggests is a surveillance-driven risk of diagnosis. These successful subjects with weight loss maintenance reported high levels of physical activity, high levels of dietary restraint, low calorie, and fat intake, and low levels of overeating (loss of control of eating or disinhibition) . In this study population, 88% were able to keep 10% of their body weight off at year 5 and 87% at year 10. To participate in the study, weight loss greater than 30 pounds had to have been maintained for more than 1 year at the time of enrollment. It is interesting to note that an extension study of semaglutide was performed to 120 weeks, but treatment was discontinued at 68 weeks. It is worthwhile to note in both studies all participants were prescribed a reduced calorie (500 kcal/day deficit) and increased physical activity 150 min/week) regimen, which was insufficient to help preserve the initial weight loss. “There's a huge pipeline of new medications that are coming,” Dr. Melanie Jay, director of the NYU Langone Comprehensive Program on Obesity Research, tells TODAY.com. FDA approves new medication for chronic weight management. Lilly releases Zepbound (tirzepatide) single-dose vials, expanding supply and access for adults living with obesity. GLP-1 RAs have been widely researched and used as antiobesity drugs in patients with or without diabetes. However, in recent years, there has been a significant rise in the use of antiobesity medications such as GLP-1 RAs with promising results in weight loss and management 22,23. Given their effectiveness in controlling blood glucose and HbA1c levels, with additional weight loss benefits and minimal intrinsic risk of hypoglycemic episodes, GLP-1 RAs are now considered the first-line injectables for optimal glucose control in diabetic patients even before insulin treatment . And the absorption rate of semaglutide in these forms is not well understood. Compounded semaglutide comes in a variety of dosage forms beyond injections. This includes “microdoses” — much smaller doses than those approved by the FDA. When Kessler reached his personal weight-loss target, he was developing some slight abdominal pains, so he decided to stop. Whereas in compounded medicines, the active ingredients are manufactured abroad, shipped in bulk, and distributed to compounding pharmacies through middlemen. "A drug that's been approved by the brand name manufacturers…There are inspections, there's standards to make sure what's in the injectable actually matches what's on the label. The FDA's on top of it," says Kessler.