Ozempic has become a notable name in both diabetes care and weight loss, but it is not the only option available. Whether you are seeking fewer side effects, better insurance coverage, or a different mechanism of action, there are several scientifically supported alternatives, including both pharmaceuticals and lifestyle changes. The "best" option depends on individual factors such as side effects, insurance coverage, dosing preference (oral vs. injection), and long-term health goals.
Understanding Ozempic
Ozempic is the brand name for semaglutide, a GLP-1 receptor agonist administered via weekly subcutaneous injections. Developed by Novo Nordisk, the medication received FDA approval in December 2017 for managing type 2 diabetes in adults. It mimics the effects of the glucagon-like peptide-1 (GLP-1) hormone, which helps manage blood glucose levels post-meal.
Mechanism of Action
Semaglutide operates by targeting three key physiological processes:
- Stimulates insulin secretion: When blood sugar levels rise, Ozempic prompts the pancreas to release insulin.
- Suppresses glucagon: It reduces the hormone that causes the liver to release stored glucose into the bloodstream.
- Slows gastric emptying: This delays how quickly food leaves the stomach, leading to a feeling of fullness and more stable blood sugar spikes after eating.
FDA-Approved Uses
Currently, Ozempic is approved for:
- Improving glycemic control in adults with type 2 diabetes.
- Reducing the risk of major cardiovascular events like heart attack, stroke, or death in adults with type 2 diabetes and known heart disease.
Patients typically start with a 0.25 mg dose once weekly for four weeks, then escalate to a 0.5 mg weekly dose. Depending on individual glycemic targets, the dosage may increase to 1 mg or even 2 mg per week.
Read also: Transformations with Ozempic
Dual Benefit: Diabetes Management and Weight Loss
While not officially labeled as a weight-loss drug under the Ozempic brand, studies show that patients frequently experience significant reductions in body weight. In the SUSTAIN-7 trial, individuals taking 1 mg of semaglutide lost an average of 4.6 kg (10.1 lbs) over 40 weeks compared to 1.9 kg (4.2 lbs) for those on dulaglutide 1.5 mg.
Off-Label Popularity
Although not FDA-approved for weight loss under the Ozempic label, semaglutide's active ingredient is marketed under another brand, Wegovy, specifically for obesity management. Word-of-mouth success stories have vaulted Ozempic into broader, off-label use for weight reduction, even among people without diabetes. About a quarter of Ozempic prescriptions are prescribed to people without diabetes.
GLP-1 Medication Alternatives to Ozempic
Mounjaro (Tirzepatide)
Developed by Eli Lilly and approved by the FDA in 2022, Mounjaro operates through dual action: it activates both the GIP and GLP-1 receptors. This dual agonist approach has shown amplified effects in both blood glucose reduction and weight loss when compared to single agonist GLP-1 drugs like Ozempic.
In the SURPASS-2 study, Mounjaro 15 mg reduced A1C by 2.3% compared to 1.86% with semaglutide (1 mg) over 40 weeks. Participants lost up to 13.1% of their body weight on Mounjaro 15 mg, versus 6.7% with semaglutide. Weekly injections, similar to Ozempic, and a titration schedule make it familiar to those already on GLP-1 analogs.
Trulicity (Dulaglutide)
Trulicity, also from Eli Lilly, is a once-weekly GLP-1 receptor agonist introduced in 2014. It binds to the same receptors as Ozempic but features a simplified pen that doesn't require dose dialing or needle handling. The AWARD trial series demonstrated A1C reductions between 0.7% and 1.6% depending on dosage and patient background. Weight changes were modest, typically between a 2 to 6 pound loss over six months. It can also lower your risk of stroke, heart attack and other cardiovascular events.
Read also: Ozempic Meal Plan
Rybelsus (Oral Semaglutide)
Rybelsus is the only oral formulation of semaglutide currently available, offering a needle-free alternative to Ozempic with similar efficacy at managing type 2 diabetes. In the PIONEER 4 trial, 14 mg daily doses led to A1C reductions of 1.2%-comparable to Ozempic at standard doses. Avg. weight loss was 8.2 lbs (3.7 kg), closely aligned with injectable GLP-1s. Absorption depends on taking it with water first thing in the morning, followed by a minimum 30-minute fasting period-compliance plays a vital role in effectiveness.
Victoza (Liraglutide)
Approved in 2010, Victoza was one of the earliest daily GLP-1 receptor agonists. Its longevity in the market gives it a strong record of safety, with consistent data on heart health benefits for people with type 2 diabetes. The LEADER trial showed a 13% reduction in major adverse cardiovascular events over 3.5 years. A1C reduction ranges from 0.6% to 1.5%, depending on dose and baseline glucose levels. Although it requires daily injection, its cardiovascular profile and lower cost make it a contender for long-term management.
Bydureon BCise (Extended-Release Exenatide)
Bydureon BCise delivers exenatide, a synthetic version of a hormone found in Gila monster venom. This once-weekly formulation steadily releases medication and was designed to minimize peak-and-trough effects. Phase 3 trials showed an average A1C drop of around 1.1% over 24 to 30 weeks. Patients typically lost between 2 to 6 pounds, with greater effects in combination with metformin. User-friendly auto-injectors and over a decade of real-world data give Bydureon appeal for individuals seeking a stable option with minimal daily decision fatigue. Exenatide, the active ingredient in Bydureon BCise, was the first GLP-1 medication to be approved by the FDA.
Byetta (Exenatide)
Byetta is an injectable GLP-1 medication with the same active ingredient as Bydureon BCise. Unlike Ozempic and other GLP-1 medications which are usually taken once a day or once a week, Byetta is injected twice daily before morning and evening meals to help control blood sugar spikes. Dosing typically starts at 5 mcg twice per day. A 200-person study found that participants taking 5 mcg of Byetta lost about 6 lbs after 6 months, while patients on a 10 mcg dose lost around 7 pounds.
GLP-1 Medication Alternatives Approved for Weight Loss
Wegovy (Semaglutide for Weight Loss)
Wegovy uses the same active compound as Ozempic but at higher doses (up to 2.4 mg weekly) and is specifically indicated for chronic weight management in adults with obesity or overweight plus a comorbidity. Wegovy was also approved by the FDA in 2022 for obesity and overweight. The STEP 1 trial revealed a mean weight loss of 14.9% over 68 weeks in non-diabetic participants. Significant reductions in waistline and blood pressure were recorded, alongside improved glycemic parameters in prediabetic subjects. Though its use hinges on weight-focused outcomes rather than glucose, individuals managing both weight and metabolic health see dual benefits. The standard Wegovy dosage is 2.4 mg per week, while Ozempic’s dosage is a maximum of 2 mg per week.
Read also: Alonso's Health Journey
Saxenda (Liraglutide)
Saxenda is a GLP-1 medication that is prescribed for weight loss. It has the same active ingredient (liraglutide) as the diabetes drug Victoza, but at a higher dose - the maximum dose for Saxenda is 3 mg per day, while the maximum dose for Victoza is just 1.8 mg per day. Patients on Saxenda lost between 5-10% of their body weight during a 56-week clinical trial. Unlike Wegovy and Ozempic, Saxenda requires a daily injection.
Zepbound (Tirzepatide)
Zepbound is a higher-dose version of Mounjaro, but is prescribed for weight loss instead of type 2 diabetes. It can also treat obstructive sleep apnea (OSA) in people with obesity. Like Ozempic, Zepbound is injected once weekly. Unlike Ozempic (which is a GLP-1 receptor agonist), Zepbound targets both GLP-1 and GIP receptors. Typical dosing for Zepbound starts at 2.5 mg and may increase depending on how the patient responds to the medication.
Non-GLP-1 Medication Alternatives
Metformin
Metformin remains the foundational therapy for type 2 diabetes because of its long-standing efficacy, low cost, and extensive clinical history. While it doesn't belong to the GLP-1 class, it's often the first alternative or complement to drugs like Ozempic. It reduces A1C by approximately 1.0% to 1.5% in monotherapy. Evidence from the UKPDS study supports its role in reducing diabetes-related endpoints, including myocardial infarction and all-cause mortality. Available in extended-release and immediate-release versions, Metformin also contributes modest weight reduction or, at a minimum, weight neutrality.
Other Weight Loss Medications
- Phentermine: The oldest and most widely used weight loss medication. It was originally used as a short-term medication to jump-start weight loss, but now newer medical guidelines have added it to long-term therapy.
- Topiramate: Can be combined with phentermine to decrease appetite and cravings.
- Naltrexone-bupropion: Combines an opioid receptor antagonist with an antidepressant to affect the pleasure-reward areas of the brain and thereby decrease cravings and appetite.
- Orlistat: A lipase inhibitor that comes in a capsule. Undigested fat is then passed through the body.
- Setmelanotide: A melanocortin-4 receptor agonist indicated for chronic weight management in adult and pediatric patients six years and older, with obesity due to certain rare genetic disorders.
- Plenity: Consists of a capsule that releases a biodegradable, super-absorbent hydrogel into the stomach. The gel helps to increase satiety, enabling the person to eat less.
Natural Alternatives to Ozempic
If you don’t qualify for Ozempic, don’t want to take medication, are concerned about side effects, or simply cannot with needles, you can consider natural alternatives to Ozempic, Wegovy®, and other glucagon-like peptide-1 receptor agonists (GLP-1 medications.
Lifestyle Changes
- Consuming small, frequent healthy meals and snacks: Consuming small, frequent healthy meals and snacks throughout the day can help you manage hunger cues. It is recommended to consume various foods, including starches, proteins, and fats and advises against swearing off things you love within moderation.
- Intuitive Eating: Tuning into feelings of fullness and eating when you’re hungry can be helpful. A 2024 study suggested that women who followed intuitive eating patterns were more likely to stabilize their weight and display fewer disordered eating habits.
- High-Protein Diet: High-protein diets help manage weight and food noise as proteins keep you feeling full longer and curb cravings. Good ways to add more protein to your diet include lean meats, eggs, beans, and nuts.
- Fiber-Rich Foods: Fiber-rich foods reduce food noise by adding bulk to your meals without extra calories and slowing digestion, which helps control hunger. Incorporating vegetables, fruits, whole grains, and beans into your diet is beneficial for overall health, including weight management and reducing cravings. A small 2023 study of 72 people indicated a link between increasing dietary fiber and weight loss.
- Regular Exercise: Exercise can temporarily suppress your appetite by lowering hunger hormones and boosting the ones that make you feel full. It also helps with stress, which is often a big trigger for food cravings.
- Stress Management: Stress can influence eating behavior, including consuming foods high in fat, sugar, and calories. Mindfulness can be a possible solution. Taking deep breaths, taking a break for a few minutes, or taking a mindful walk can help.
- Quality Sleep: Insufficient sleep could contribute to weight management issues. Reduced sleep quality and quantity can lead to more snacking, higher calorie consumption, and more snacking, especially on foods high in fat and carbohydrates. When you’re tired, your hunger hormones go haywire, making you crave more food. Aim for seven to nine hours of solid sleep, and try to wind down before bed with something relaxing.
Specific Natural Alternatives
- Protein: Eating a high-protein diet can reduce your appetite, help you feel fuller, and reduce cravings. Experts suggest aiming for 100 grams of protein a day when losing weight.
- Fiber: Fiber can dilute calories in a meal, which increases satiety (the feeling of fullness). Fiber has many health benefits beyond weight loss, including gut health, lowering cholesterol, and reducing the risk of heart disease, stroke, and type 2 diabetes.
- Water: Drinking water before a meal can aid weight loss by affecting hunger hormones, helping you feel fuller, and keeping you hydrated.
- Sleep: Aim for at least seven hours of sleep a night to avoid the negative impact of sleep deprivation on hunger hormones.
- Reduced Stress: Lowering stress levels can reduce appetite, cravings, and the tendency to store belly fat.
- Berberine: More research is needed on berberine’s weight loss effects.
- Magnesium: Magnesium deficiency can lead to chronic low-grade inflammation, which may cause obesity, cardiovascular diseases, diabetes, depressive symptoms, and sleep disorders (which are also linked to weight gain).
- Green Tea: Green tea has anti-inflammatory, antioxidant, and anti-cancer properties, and it might play a role in weight management. The combination of caffeine and catechins may increase energy metabolism and lead to weight loss.
The Discovery of BRP
Stanford Medicine researchers have identified a naturally occurring molecule, BRP, that appears similar to semaglutide in suppressing appetite and reducing body weight. The 12-amino-acid BRP peptide suppresses appetite and reduces weight gain in mice and pigs without causing nausea or food aversion. The newly discovered molecule, BRP, acts through a separate but similar metabolic pathway and activates different neurons in the brain. When the researchers tested the effect of BRP on lean mice and minipigs (which more closely mirror human metabolism and eating patterns than mice do) they found that an intramuscular injection of BRP prior to feeding reduced food intake over the next hour by up to 50% in both animal models. Obese mice treated with daily injections of BRP for 14 days lost an average of 3 grams - due almost entirely to fat loss - while control animals gained about 3 grams over the same period.
The Phenomenon of "Food Noise"
"Food noise" refers to constant thoughts about food, even when you’re not hungry. GLP-1 drugs like Ozempic can lower the volume of these signals. They make you feel fuller for longer, slow down how fast food leaves your stomach, and even reduce cravings by acting on parts of the brain that control appetite. Basically, they quiet the chatter about food, so it’s easier to focus on eating when you actually need to. Several healthy habits can help you naturally manage hunger and quiet “food noise” without medication. These include eating high fiber and high protein foods, getting regular exercise and quality sleep, reducing stress, and avoiding extremely restrictive diets.
Important Considerations
- Insurance Coverage: Insurance coverage varies and will affect many patients’ choices about going on weight loss medications.
- Side Effects: Be aware of potential side effects. Switching from Ozempic to another treatment should be done with guidance from your healthcare provider.
- Compounded Medications: The FDA warns against buying medications from any source other than a state-licensed pharmacy and has banned the sale of “counterfeit” semaglutide and tirzepatide.
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