Phentermine is a widely prescribed weight loss medication that has been around for a long time and it was approved by the Food and Drug Administration (FDA) in 1959 for the short-term treatment of obesity in adults. However, due to its potential side effects and risk of addiction, many individuals seek alternatives. This article explores prescription drugs, over-the-counter options, herbal remedies, and lifestyle changes that can serve as effective substitutes for phentermine.
What is Phentermine?
Phentermine, commonly known by its brand name Adipex-P®, is a sympathomimetic amine and part of a drug class called anorectics. It's a central nervous system (CNS) stimulant that suppresses your appetite. Phentermine may help reduce your food cravings as an appetite suppressant and increase your metabolic rate so you burn body fat. It’s also chemically related to amphetamine and is a schedule IV controlled substance because of the potential risk for addiction.
Patients prescribed phentermine for weight loss must have a body mass index (BMI) of 30 or greater or a BMI of 27 or greater and at least one weight-related condition like high blood pressure (hypertension), diabetes, or high cholesterol. Because phentermine is a controlled substance with a risk of abuse and dependence, those with a history of substance abuse disorder can’t take it at all. It also comes with a host of potential side effects, like increased heart rate, hypertension, restlessness, agitation, dry mouth, headache, and insomnia, that may make you a bit hesitant about trying the popular obesity drug.
Prescription Alternatives
GLP-1 Receptor Agonists
Glucagon-like peptide-1 receptor agonists (GLP-1s) are a class of drugs that mimic the GLP-1 incretin hormone, which controls appetite and hunger. They also help manage blood sugar levels by supporting the pancreas in making enough insulin after you eat. GLP-1s work to slow digestion, making you feel full longer, which reduces calorie intake and suppresses appetite.
Wegovy® (Semaglutide)
Wegovy, a brand name for semaglutide, is a once-weekly prescription injectable medication approved by the FDA in June 2021 for long-term weight management in adults and children aged 12 years or more with obesity (BMI ≥30 for adults, BMI ≥ 95th percentile for age and sex for children) or some adults with excess weight (BMI ≥27) who also have weight-related medical problems. Manufactured by Novo Nordisk, Wegovy has demonstrated significant weight loss results in clinical trials.
Read also: Weight Loss Approaches in Sacramento
In a 68-week double-blind trial published in The New England Journal of Medicine in 2021, participants who received a once-weekly 2.4 mg dose of semaglutide lost an average of 14.9% of their body weight compared to the placebo group’s 2.4%. Moreover, the semaglutide group showed improvement in risk factors of cardiovascular events like heart attack and stroke.
Common side effects of semaglutide include nausea, diarrhea, vomiting, constipation, stomach (abdomen) pain, headache, tiredness (fatigue), upset stomach, dizziness, feeling bloated, belching, gas, stomach flu, and heartburn.
Food may affect the absorption of semaglutide when taken orally. Talk to your doctor before using alcohol together with semaglutide.
Ozempic® (Semaglutide)
Ozempic may be a more familiar name to some patients.
Saxenda® (Liraglutide)
Saxenda, or liraglutide, is another injectable medication in the GLP-1 drug class, also manufactured by Novo Nordisk. Approved by the FDA in 2014 for treating obesity in adults and, in 2020, for children 12 years and older with obesity, Saxenda is intended for long-term weight management.
Read also: Safe Diet Pills
A review of five randomized, placebo-controlled trials published in 2017 found that liraglutide, when taken with a reduced-calorie diet and increased physical activity, consistently resulted in about a 9- to 13-pound weight loss.
Common side effects of liraglutide include nausea, diarrhea, constipation, vomiting, injection site reaction, low blood sugar (hypoglycemia), headache, tiredness (fatigue), dizziness, stomach pain, and change in enzyme (lipase) levels in your blood.
Trulicity® (Dulaglutide)
Dulaglutide, the active ingredient in Trulicity, is a GLP-1 receptor agonist approved for diabetes management and to reduce cardiovascular events in adults with type 2 diabetes. While primarily a diabetes medication, Trulicity can be prescribed off-label for weight loss in adults with overweight or obesity.
In a 52-week study published in 2021, patients with inadequately controlled type 2 diabetes who were given once-weekly injections of dulaglutide lost about 10 pounds compared to those on a lower dose.
Common side effects of Trulicity include nausea, diarrhea, vomiting, abdominal pain, decreased appetite, indigestion, and fatigue.
Read also: Comprehensive Study: Metformin and Phentermine/Topiramate
Important Note about GLP-1s
GLP-1s come with a black box warning due to the risk of thyroid C-cell tumors, which developed in mice during testing. They should not be used if you or a family member has a history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2).
GIP and GLP-1 Receptor Agonists
Zepbound® (Tirzepatide)
Zepbound, contains tirzepatide and is approved to treat obesity in adults with a BMI of 30 or greater. It is both a GLP-1 and a GIP receptor agonist. Like semaglutide, it works by reducing appetite and is meant to be used in combination with diet and exercise to lose weight.
Mounjaro® (Tirzepatide)
Mounjaro, another injectable medication containing tirzepatide, is currently FDA-approved to treat type 2 diabetes. However, healthcare professionals often prescribe it off-label for weight loss due to its effectiveness. Tirzepatide belongs to a drug class called a glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like peptide 1 (GLP-1) receptor agonist. It mimics both the GLP-1 and GIP hormones, working in two ways to help control blood-sugar levels.
In a 72-week phase 3 clinical trial, participants lost up to 22.5% of their body weight on tirzepatide. Of those on the 15 mg dose, 63% achieved at least 20% body weight reductions.
Common side effects of tirzepatide include nausea, diarrhea, decreased appetite, vomiting, constipation, indigestion, and stomach (abdominal) pain. It can also decrease the efficacy of oral birth control pills, so alternative birth control methods should be discussed with a healthcare provider.
Phentermine-Topiramate (Qsymia)
Topiramate can be combined with phentermine to decrease appetite and cravings. Adults with migraines and obesity are good candidates for this weight-loss medication. Some patients may lose an average of 5-10% of body weight. Daily doses with four strengths start at 3.75 mg/23 mg to 15 mg/92 mg. Side effects include abnormal sensations, dizziness, altered taste, insomnia, constipation, and dry mouth.
Naltrexone-Bupropion (Contrave)
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. Start with a daily dose of one 8/90 mg tablet and gradually increase to four tablets a day. The most common side effects include nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth, and diarrhea.
Setmelanotide
Setmelanotide is 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.
Over-the-Counter Options
Orlistat (Alli®)
Orlistat, sold under the brand name Alli®, is the only FDA-approved over-the-counter (OTC) weight loss aid for adults 18 and older with a BMI of 25 or more. Alli belongs to a class of drugs called lipase inhibitors, blocking the intestines from absorbing about 25 percent of the fat you eat. The unabsorbed fats are then eliminated through bowel movements.
Orlistat is an oral pill typically taken within an hour of a meal up to three times a day. Common side effects include stomach pain, upset stomach, oily anal discharge, gas, oily stools, increased bowel movements, headaches, back pain, and menstrual changes.
Plenity
A medical device rather than a medication, Plenity was FDA-cleared in 2019 for people with a BMI of 25 to 40. It 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 Phentermine Alternatives and Supplements
While many supplements claim to curb sugar cravings, trigger fat loss, or offer a money-back guarantee, these claims are often unsubstantiated. Weight-loss supplements that boast fat-burning, appetite-suppressing, and metabolism-boosting properties may do more harm than good.
Be cautious of OTC diet pills that include thermogenic ingredients like cayenne pepper, green tea extract, green coffee, vitamin B6, and guarana. Studies on the safety and effectiveness of natural supplements for weight loss suggest that they are unlikely to contribute to meaningful weight loss and in some cases may be harmful.
The FDA regulates supplements, but they do not need to pass through the same strict drug guidelines as prescription medications before being marketed, it’s important to talk to a health care professional before beginning any new supplement, especially those that profess to be natural appetite suppressants or over-the-counter phentermine alternatives.
Other natural ingredients to be cautious of include L-theanine, glucomannan, L-tyrosine, chromium picolinate, garcinia cambogia, phenylalanine, and rhodiola rosea. Be wary of name-brand weight-loss pills that claim to increase energy levels and have fat-burning abilities, such as PhenGold, PhenQ, Phen24, PrimeShred, Leanbean®, and Trimtone.
Lifestyle Changes
A treatment plan for obesity can comprise multiple forms of treatment, including medications, diet, exercise, and/or surgery. All weight loss medications work best in the context of a healthy eating plan and exercise.
The Future of Weight Loss Medications
With fervent consumer demand for weight loss medications and rising obesity rates, more medications are expected to enter the market in the coming years. Pharmaceutical platforms predict one to two GLP-1 launches annually starting in 2026 specifically for obesity.
Lilly is developing orforglipron, an oral GLP-1 inhibitor that completed a Phase 3 clinical trial in early 2025, and retatrutide, which targets GLP-1, GIP, and glucagon. Amgen is developing MariTide, a monoclonal antibody designed to increase GLP-1 receptor activity while reducing GIP receptor activity.
Researchers continue to study hormones that play a role in appetite for other ways to target obesity with medication, including peptide tyrosine-tyrosine (PYY) and cholecystokinin (CCK). With more options available, doctors will be increasingly able to personalize treatments.
Important Considerations
Insurance Coverage
Insurance coverage varies and will affect many patients’ choices about going on weight loss medications. GLP-1s are notoriously costly. The Kaiser Family Foundation estimates the annual net price of Wegovy at $13,600 and are not covered by insurance.
Counterfeit Medications
The FDA warns against buying medications from any source other than a state-licensed pharmacy. In April 2025, they banned the sale of “counterfeit” semaglutide and tirzepatide, which are compounded medications not made or packaged by the original manufacturers.
Vitamin and Mineral Support
While no specific vitamin or supplement is considered a “treatment” for obesity or overweight, certain ones help support metabolic health. For example, studies suggest that calcium and vitamin D may play a role in regulating belly fat.
Antidepressants and Weight
Some antidepressants are associated with weight gain, while others are weight-neutral or even weight-negative. Bupropion (Wellbutrin) is considered weight-negative and is prescribed both to assist in weight loss and to treat depression.
tags: #phentermine #alternatives