When people think about prescription weight loss medications today, GLP-1 medications like Wegovy, Zepbound, and Saxenda tend to dominate the conversation — and for good reason. They are highly effective and generally well tolerated. But GLP-1s are not the only tools available, and they are not the right fit for every patient.
Long before GLP-1 medications existed, physicians were already treating obesity as a chronic medical condition using FDA-approved medications. At Missouri Metabolic Health, we regularly use these "first generation" obesity medications — phentermine, Qsymia, and Contrave — on their own, in combination with each other, or alongside GLP-1 therapy. If you're managing obesity, prediabetes, metabolic syndrome, PCOS, or type 2 diabetes, understanding these options can help you and your provider choose the most effective, affordable, and sustainable treatment plan for you.
What Obesity Medicine Is Actually Trying to Achieve
Before diving into specific medications, it helps to understand the goal of obesity treatment. Obesity medicine isn't about achieving a number on the scale for its own sake — it's about reducing excess body fat enough to prevent and treat weight-related health conditions like type 2 diabetes, PCOS, fatty liver disease, high blood pressure, and sleep apnea.
Clinically, we generally look for at least 5% total body weight loss after three months on a maximally tolerated dose as a sign that a medication is working. Many patients want — or medically need — more than that, and greater weight loss (10%, 20%, or more) often brings even greater metabolic benefit. Newer GLP-1 medications can produce 15–20% total body weight loss for many patients, but the medications below remain valuable options, especially when cost, side effects, medication shortages, or personal preference make GLP-1 therapy less practical.
Phentermine: The Original FDA-Approved Weight Loss Medication
Phentermine was the very first obesity medication approved by the FDA, back in 1959, and it's still widely used today.
How it works: Phentermine is a stimulant medication that helps suppress appetite. Because it's a controlled substance, it requires a prescription, though its potential for misuse is considered very low.
What to expect:
- Taken orally, once daily, in the morning (taking it too late can interfere with sleep)
- Very affordable — often available for around $20/month or less in generic form, even without insurance
- Technically FDA-approved for short-term (three month) use, but commonly prescribed longer-term by obesity medicine and primary care physicians, since obesity is a chronic condition
- Average weight loss in the range of 5–10% of total body weight
Common side effects include headache, dry mouth, a racing heart, and occasionally anxiety or irritability — effects similar to a stimulant like caffeine. Patients who don't tolerate phentermine well sometimes do better on a related medication, diethylpropion, which is shorter-acting and can be dosed with meals throughout the day.
Who should avoid it: Phentermine isn't appropriate for people with uncontrolled high blood pressure, a history of heart disease (including stroke, heart failure, or atrial fibrillation), glaucoma, or uncontrolled hyperthyroidism.
Qsymia: A More Powerful Combination Option
Approved by the FDA in 2012, Qsymia combines phentermine with topiramate, an anti-seizure medication that also affects appetite regulation. The combination has an additive effect, and many patients lose 12–15% of their total body weight — meaningfully more than phentermine alone.
What to expect:
- Works through similar appetite-suppressing pathways in the brain, enhanced by topiramate
- FDA-approved for long-term use, with no state restrictions on prescribing duration
- Brand-name Qsymia can be expensive, but manufacturer delivery programs can bring costs down to roughly $89 for a 30-day supply (about $70/month with a 90-day supply)
- A more affordable alternative: some physicians prescribe phentermine and topiramate separately, at slightly different doses, which can lower out-of-pocket cost
Side effects specific to the topiramate component include an increased risk of kidney stones (stay well hydrated), fatigue or drowsiness at higher doses, a metallic or altered taste (which many patients notice most with carbonated beverages — helpful if you're trying to cut back on soda), and occasional tingling sensations in the fingers or toes, which resolve after stopping the medication.
Important safety note: Topiramate is teratogenic, meaning it can cause birth defects such as cleft lip and cleft palate. Anyone who could become pregnant should be on effective contraception while taking Qsymia.
Contrave: Targeting Cravings and Emotional Eating
Approved in 2014, Contrave combines bupropion (also known by the brand name Wellbutrin) with naltrexone. Rather than primarily suppressing appetite, Contrave is often most helpful for patients struggling with food cravings, food noise, and emotional eating, because it targets the brain's food reward pathway.
What to expect:
- Bupropion is also used to treat depression, anxiety, ADHD symptoms, and can support smoking cessation
- Naltrexone blocks opioid receptors and is commonly used to reduce alcohol cravings
- Can be a strong option for patients who also want support with mood, smoking, or alcohol intake
- Brand-name-only, though delivery programs can bring the cost down to around $99/month, and generic components can be prescribed separately for additional savings
Common side effects include nausea (especially when starting), headache, palpitations, and mild stimulating effects from bupropion, which is why it's best taken earlier in the day.
Who should avoid it: Contrave is not appropriate for anyone with a history of seizures, since bupropion can lower the seizure threshold. It also cannot be combined with opioid medications — including over-the-counter kratom or 7-OH products — as this combination can trigger precipitated withdrawal and severe flu-like symptoms.
How These Medications Fit Alongside GLP-1 Therapy
It took from 1959 to 2014 for the FDA to approve these three oral obesity medications — a stretch of more than 50 years. By contrast, the last decade alone has brought a wave of GLP-1 medications, including Saxenda, Wegovy, oral Wegovy, higher-dose Wegovy, and Zepbound, with more (like cagrilintide-based combinations and retatrutide) on the way.
That doesn't mean phentermine, Qsymia, and Contrave are outdated. In practice, we use them in several situations:
- As an add-on to GLP-1 therapy for patients who've plateaued and want additional support toward their health goals
- As a bridge or maintenance strategy for patients who can't afford long-term GLP-1 treatment — starting with a GLP-1, then transitioning to a first-generation medication for maintenance
- During medication shortages, when GLP-1 supply is limited
- As a first-line option for patients who prefer an oral medication, have a specific contraindication to GLP-1s, or want to address cravings, mood, or cost first
Obesity is a multifactorial, chronic condition, and having multiple tools in the toolbox — rather than a one-size-fits-all approach — is what allows treatment to be personalized.
An Honorable Mention: Metformin
Metformin isn't officially classified as an obesity medication — it doesn't suppress appetite, reduce food noise, or increase fullness. But it does treat the underlying insulin resistance that plays a role in weight struggles for many patients, which makes it a valuable adjunct for improving overall metabolic health. It's generic, inexpensive, and has decades of safety data behind it, which is why it's often part of a broader treatment plan for patients with prediabetes, PCOS, or metabolic syndrome.
Finding the Right Medication for Your Metabolic Health
There is no single "best" weight loss medication — the right choice depends on your health history, your goals, your budget, and how your body responds to treatment. Whether you're managing PCOS, prediabetes, metabolic syndrome, type 2 diabetes, or obesity, a thoughtful, individualized plan matters more than chasing the newest medication on the market.
At Missouri Metabolic Health, we specialize in treating and preventing metabolic conditions through a combination of lifestyle optimization and safe, effective medical treatment — including phentermine, Qsymia, Contrave, metformin, and GLP-1 medications, used alone or in combination based on what's right for you.
Ready to explore your options? [Schedule a telehealth consultation with Missouri Metabolic Health] to build a personalized plan for lasting metabolic health.
This article is provided for general educational purposes and is not a substitute for personalized medical advice. Please consult your physician or a qualified obesity medicine provider before starting or changing any medication.
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