The rise in popularity of GLP-1 medications for weight loss and diabetes management has sparked a significant interest in understanding how these drugs work and what alternatives exist. This article aims to provide a comprehensive overview of GLP-1 medications, explore potential alternatives, and discuss important considerations for those seeking weight management solutions.
Understanding GLP-1 and Its Role in Weight Management
Many people hadn’t even heard of GLP-1 before a couple of years ago. And yet we’ve had it in our bodies all along. GLP-1, or glucagon-like peptide-1, is a natural hormone produced in the gut that is released after we eat. It plays a crucial role in regulating appetite and blood sugar levels. GLP-1 stimulates the release of insulin, a hormone that helps transport glucose from the bloodstream into the body's cells for energy.
Prescription GLP-1 medications, such as semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro, Zepbound), mimic the effects of this natural hormone. They slow down digestion and promote a feeling of fullness, leading to reduced food intake and subsequent weight loss, says Supriya Rao, MD, a doctor in internal medicine, gastroenterology, obesity medicine, and lifestyle medicine in Boston. These medications have been game changers in both obesity and diabetes management.
How GLP-1 Medications Work
GLP-1 medications work through several mechanisms:
- Slowing Gastric Emptying: They delay the movement of food from the stomach to the small intestine, prolonging the feeling of fullness.
- Appetite Regulation: They act on the brain's appetite control centers, reducing hunger signals and food cravings.
- Insulin Production: For individuals with diabetes, GLP-1s stimulate insulin production when blood sugar levels are high, while also reducing the liver's glucose production.
The Satiating Nutrient Trifecta
Medications might increase GLP-1, but you can also do that with food that fills you up and keeps you satisfied, says Tara Collingwood, a sports dietitian and American College of Sports Medicine (ACSM)-certified personal trainer in Orlando. The trifecta of satiating nutrients is protein, fat, and fiber. These all slow the movement of food through the digestive tract and are foods that increase GLP-1. “This is the not-so-secret secret,” Collingwood says. Eating whole grains, fruits, vegetables, and lean proteins will activate that fullness factor. In fact, research shows that fiber stimulates the release of GLP-1 to reduce hunger and appetite, which may be one reason why fiber can lead to weight loss. But although these nutrients support weight loss and maintenance, they don’t amplify GLP-1 the way medication does.
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Reasons for Seeking GLP-1 Alternatives
Given the excitement surrounding them, social media is full of food concoctions and supplements touted as “natural GLP-1s” or “nature’s Ozempic.” But do they really work and are they even safe?
While GLP-1 medications have proven effective, several factors may prompt individuals to seek alternatives:
- Cost: GLP-1 medications can be expensive, and insurance coverage may be limited. The Kaiser Family Foundation estimates the annual net price of Wegovy at $13,600.
- Supply Shortages: High demand has led to ongoing supply shortages, making it difficult for some patients to obtain their prescriptions consistently.
- Side Effects: While generally well-tolerated, GLP-1 medications can cause gastrointestinal issues like nausea, vomiting, diarrhea, and constipation.
- Insurance Coverage: Many insurance plans restrict coverage to patients with diabetes, denying coverage for those seeking it primarily for weight loss.
Prescription GLP-1 Alternatives
Searching for Ozempic alternatives can feel overwhelming when facing high costs or limited availability. While Ozempic effectively manages diabetes and weight, several other GLP-1 medications offer similar benefits, potentially at lower prices. Ozempic belongs to a class of medications called glucagon-like peptide-1 (GLP-1) receptor agonists. These drugs work by mimicking the natural hormone GLP-1, which helps regulate blood sugar levels and appetite.
Several prescription medications offer similar effects to Ozempic, either through the same mechanism of action (GLP-1 receptor agonists) or through alternative pathways.
- Rybelsus (oral semaglutide): Contains the same active ingredient as Ozempic but is available as a daily pill, making it a suitable option for those who prefer to avoid injections.
- Mounjaro (tirzepatide): A newer medication that works on both GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors, leading to greater A1C reduction and weight loss compared to Ozempic in clinical trials.
- Trulicity (dulaglutide): Another once-weekly injectable option with proven cardiovascular benefits similar to Ozempic.
- Victoza (liraglutide): Requires daily injections but also offers established cardiovascular benefits.
- Bydureon BCise (exenatide): A once-weekly injectable that was the first FDA-approved GLP-1 medication.
- Byetta (exenatide): Requires twice-daily injections before meals.
- Wegovy (semaglutide): Contains the same active ingredient as Ozempic but at higher doses specifically approved for weight loss.
- Saxenda (liraglutide): Uses the same active ingredient as Victoza but at a higher daily dose for weight loss.
- Zepbound (tirzepatide): The most powerful FDA-approved medication for weight loss, targeting both GLP-1 and GIP receptors.
Comparing Effectiveness
- Diabetes Management: Mounjaro (tirzepatide) appears more effective than Ozempic at reducing A1C levels.
- Weight Loss: Zepbound (tirzepatide) produces greater average weight reduction than semaglutide medications like Ozempic and Wegovy.
Important Considerations
- All of these medications start with lower doses that gradually increase over several weeks or months to minimize side effects.
- These medications work best as part of a comprehensive approach that includes dietary changes, regular physical activity, and behavioral modifications.
- Individual responses vary, and side effect profiles differ. Some patients may respond better to one medication than another.
Natural Approaches to Boosting GLP-1 and Supporting Weight Loss
Medications might increase GLP-1, but you can also do that with food that fills you up and keeps you satisfied, says Tara Collingwood, a sports dietitian and American College of Sports Medicine (ACSM)-certified personal trainer in Orlando.
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In addition to prescription medications, several natural strategies can help support weight loss and potentially boost GLP-1 levels:
- High-Protein Diets: High-protein diets help manage weight and reduce food cravings by increasing satiety hormones and slowing digestion. Protein requires more energy to digest than carbohydrates or fats, boosting metabolism slightly. Good protein sources include lean meats, poultry, fish, eggs, dairy, beans, and nuts.
- Fiber-Rich Foods: Fiber-rich foods add bulk without calories while slowing digestion to control hunger. Soluble fiber forms a gel-like substance in the digestive tract that delays stomach emptying, similar to GLP-1 medications' effect. Studies show that increasing dietary fiber supports weight loss and helps people adhere to calorie-restricted diets.
- Regular Exercise: Regular exercise temporarily suppresses appetite by reducing hunger hormones and increasing satiety hormones. Particularly vigorous exercise appears to reduce ghrelin, the primary hunger hormone. Beyond its immediate effects on appetite, exercise improves insulin sensitivity, supports healthy metabolism, and helps maintain weight loss long-term. Research shows that a single exercise session, as well as long-term training, can enhance GLP-1 levels in the body for those who have type 2 diabetes, according to one review and meta-analysis. (But as the review points out, some research is conflicting.) Exactly what’s going on needs further study. But it’s all the more reason to get the widely recommended amount of exercise for general health: 150 minutes (or more) of moderate-intensity exercise and 2 days of resistance training per week.
- Stress Management: Stress management helps control emotional eating triggered by elevated cortisol levels. Chronic stress increases cravings for high-calorie, high-fat "comfort foods" while potentially promoting abdominal fat storage.
- Quality Sleep: Quality sleep regulates hunger hormones that drive appetite. Insufficient sleep disrupts ghrelin and leptin levels, increasing hunger and cravings, particularly for high-carbohydrate foods.
- Balanced Eating Patterns: Balanced eating patterns rather than restrictive diets help maintain consistent energy and blood sugar levels.
The "Oatzempic" Trend
One of the great things about oats is that they’re rich in fiber, specifically a type called soluble fiber. “When oats are combined with water, they can be filling,” Collingwood says. Social media took this a step further by introducing "oatzempic," a blended concoction of a half cup of oats, one cup of water, and lime juice. Here’s the reality check: “Drinking oats this way may raise GLP-1 in the body slightly, but it’s not anything like these injections,” Rao says. The drink isn’t harmful. But it may not be tasty, either, Collingwood notes. “I’d rather just eat a bowl of oatmeal.”
Supplements as Potential GLP-1 Alternatives
In the conversation about how to increase GLP-1 naturally, there’s often talk about supplements.
Some supplements have been touted as potential "natural Ozempic alternatives," though it's important to note that they lack the robust clinical evidence supporting prescription GLP-1 medications.
- Berberine: Berberine, a compound found in several plants, has garnered attention as a potential “natural Ozempic alternative.” And a meta-analysis of 12 randomized, controlled trials shows that taking berberine leads to about a 4.5-pound weight loss and a 1-centimeter reduction in waist circumference. Some research indicates berberine might boost GLP-1 levels naturally, though evidence remains preliminary. The catch is, all these trials use different doses (from 300 to 1,500 milligrams per day) and duration (1 to 24 months), so it’s tough to know exactly what happens when you take berberine. On the other hand, the clinical trials on semaglutide (Wegovy) for weight loss have been clear: On average, people taking that medication lose 15% of their body weight over 68 weeks compared to 2.4% of body weight in those taking a placebo.
- Glucomannan: Glucomannan, a dietary fiber from konjac root, absorbs water to form a bulky fiber in the stomach, potentially increasing fullness.
Important Considerations
- These supplements may cause side effects or interact with medications, making healthcare provider consultation essential before starting any supplement regimen.
- Supplements may rely on preliminary or incomplete data, so it’s less clear what effect they will have on you.
- Unlike prescription medications, supplements don’t have to prove that they’re safe and effective, and the FDA doesn’t regulate them the same way.
- If your doctor supports you trying a supplement, look for one that’s third-party certified, which ensures that the product is labeled accurately and is free of contaminants.
Navigating Compounded GLP-1 Medications
Given the soaring demand for GLP-1s has created shortages across the country. In response, semaglutide and tirzepatide were added to the FDA Drug Shortages Database, allowing compounding pharmacies to produce generic versions. In turn, telehealth companies began selling the drugs at prices far lower than the average $1,300 per month paid for brand-name GLP-1s.
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The FDA is aware that some patients and health care professionals may look to unapproved versions of GLP-1 (glucagon-like peptide-1 (GLP-1) receptor agonists) drugs, including semaglutide and tirzepatide, as an option for weight loss. This can be risky for patients, as unapproved versions do not undergo FDA’s review for safety, effectiveness and quality before they are marketed.
A compounded drug might be appropriate if a patient’s medical need cannot be met by an FDA-approved drug, or the FDA-approved drug is not commercially available. However, compounded drugs are not FDA approved. This means the agency does not review compounded drugs for safety, effectiveness or quality before they are marketed. The agency has identified some areas of concern for compounded GLP-1 drugs. FDA is working with its state regulatory partners and will continue to communicate with compounders regarding these concerns.
Potential Risks of Compounded GLP-1 Drugs
- Improper Storage: Injectable GLP-1 drugs require refrigeration. The FDA has received complaints that certain compounded GLP-1 drugs have arrived warm or with inadequate ice packs.
- Counterfeit Products: The FDA has found compounded drugs that contain false information on the product label.
- Dosing Errors: The FDA received multiple reports of adverse events, some requiring hospitalization, that may be related to dosing errors associated with compounded injectable semaglutide products.
- Unapproved Ingredients: The agency is aware that some semaglutide products sold by compounders may be the salt forms. These salt forms, including semaglutide sodium and semaglutide acetate, are different active ingredients than are used in the approved drugs.
Recommendations for Consumers
- Carefully check labels of compounded GLP-1 drugs for warning signs such as spelling errors or incorrect addresses and ensure your medicine is provided by a licensed pharmacy and prescribed by a licensed health care provider.
- If you receive a product with a licensed pharmacy name on the label that you think might be fraudulent, contact the pharmacy to ask if it is their product.
- Talk to your doctor if you have questions about your medicines.
The Importance of a Comprehensive Approach
While medications, both prescription and over-the-counter, can play a significant role in weight management, they are most effective when combined with lifestyle modifications.
- All weight loss medications work best in the context of a healthy eating plan and exercise.
- Prescription GLP-1 medications work most effectively alongside dietary changes and regular physical activity.
- Natural approaches like high-protein diets, regular exercise, stress management, and quality sleep can enhance medication effectiveness while potentially allowing for lower medication doses.
Consulting with Healthcare Professionals
Navigating the landscape of GLP-1 medications and alternatives requires careful consideration and consultation with healthcare professionals.
What to Discuss with Your Doctor
- Reasons for Seeking Alternatives: Clearly explain why you’re seeking alternatives. Whether facing supply shortages, insurance denials, intolerable side effects, or cost concerns, being specific helps your provider identify suitable options.
- Treatment Goals: Share your treatment goals explicitly. Are you primarily focused on diabetes management, weight loss, cardiovascular protection, or a combination?
- Preferences: Discuss your preferences regarding administration method. Would you prefer an oral medication over injections? Can you manage daily medications, or do you need a once-weekly option?
- Natural Approaches and Supplements: If considering natural approaches or supplements, ask about evidence supporting their use and potential interactions with your current medications.
- Monitoring Plan: Discuss a monitoring plan to evaluate how well any alternative works for you.
The Future of Weight Loss Medications
With fervent consumer demand for weight loss medications, combined with rising obesity rates, more medications are bound for the market in the coming years. Pharmaceutical platform Ozmosi predicts one to two GLP-1 launches annually starting in 2026. specifically for obesity. Lilly is developing at least two new options. The first, orforglipron, is an oral GLP-1 inhibitor that completed a Phase 3 clinical trial in early 2025. It could provide a welcome alternative for people who do not want injections. Phase 3 results expected soon. at 36 weeks. The other, retatrutide, targets GLP-1, GIP, and glucagon. At this writing, it is in Phase 3 clinical trials. In Phase 2, participants lost up to 24.2% of body weight at 48 weeks. Amgen is developing MariTide, a monoclonal antibody designed to increase GLP-1 receptor activity while reducing GIP receptor activity. The once-monthly injection entered Phase 3 clinical trials in March 2025. Researchers continue to study hormones that play a role in appetite for other ways to target obesity with medication. Those of interest include not only GLP-1, but also peptide tyrosine-tyrosine (PYY) and cholecystokinin (CCK). With more options available, doctors will be increasingly able to personalize treatments.
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