Semaglutide alternatives: what actually works and what to watch for
Semaglutide changed the conversation about weight loss and blood sugar control, but it’s not the only tool. If you’re curious about other options—because of cost, side effects, availability, or medical reasons—this guide lists real alternatives and how they compare in plain language.
Drug alternatives: newer and older options
Tirzepatide (brand names Zepbound/Zynquista) is the closest head-to-head alternative. Large trials such as SURMOUNT showed it can produce greater average weight loss than semaglutide at some doses—people saw roughly mid-teens to around 20% body-weight drops in higher-dose studies. It’s also a diabetes drug, so it helps blood sugar and appetite.
If tirzepatide isn’t right for you, other drug classes can help with weight or diabetes: SGLT2 inhibitors (empagliflozin, canagliflozin) lower blood sugar and reduce heart risk but give modest weight loss. DPP-4 inhibitors (sitagliptin) are gentle on side effects but don’t cause much weight change. Older, cheaper options like metformin can help with weight stabilization and insulin resistance in some people, especially those with prediabetes.
For weight specifically, non-GLP-1 medications still used include orlistat (reduces fat absorption), phentermine-topiramate (appetite suppressant combo), and bupropion-naltrexone. These have different side-effect profiles and work differently from GLP-1s—some affect hunger, others affect fat absorption or reward circuits. Your doctor will weigh benefits versus risks for your case.
Non-drug options and practical issues
Bariatric surgery remains the most effective option for substantial, long-term weight loss and diabetes remission for people who meet surgical criteria. Lifestyle changes—focused, supervised programs that combine diet, exercise, and behavioral counseling—can also produce significant results, especially when paired with medical therapy.
Cost and access matter. Semaglutide and tirzepatide can be expensive and sometimes require prior authorization. Cheaper alternatives like metformin or SGLT2 drugs may be covered by insurance more easily. Avoid buying prescription meds from unverified online pharmacies. Always use a licensed prescriber and a reputable pharmacy—our site has guides on safe online buying.
Side effects differ: nausea and GI upset are common with GLP-1s and tirzepatide. SGLT2s carry a risk of genital infections and, rarely, dehydration. Appetite suppressants can raise heart rate or blood pressure in some people. That’s why reviewing your medical history—heart disease, kidney function, pregnancy plans—matters before choosing a drug.
How to choose: start with your main goal (weight loss vs. blood sugar control), medical history, and budget. Ask your clinician about expected weight loss ranges, side effects, and how long you should try a medication before judging if it works. If you’re switching because of side effects, discuss gradual changes and monitoring plans.
Want help comparing options for your situation? Talk to your doctor or a specialist—endocrinologists and bariatric teams see these choices every day and can match the right option to your goals.

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