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September 28, 2023
Losing weight can be one of the most challenging things to take on, especially the older we get. Fortunately, a lot of research and development has gone into facilitating that process, and some of the best ways to boost weight loss come in the form of a fat-burning supplement or weight loss drug.
Out of your options, two of the most effective weight loss drugs today are semaglutide and phentermine. These two weight loss medications work very differently, but both have helped countless people on their weight loss journey. In this article, we will break down semaglutide vs. phentermine to help you determine the best option for your weight loss goals.
Table of Contents
Semaglutide is a compound part of a class of medications called glucagon-like peptide-1 (GLP-1) receptor agonists. GLP-1 is a naturally occurring hormone produced in the intestines and released into the gastrointestinal tract as a response to eating.
The primary role of semaglutide is to increase insulin production, which lowers blood sugar levels. As such, semaglutide was initially designed to treat type 2 diabetes mellitus. However, during clinical trials, they noticed it had remarkable weight loss properties, which led to its use for obesity and chronic weight management.
Semaglutide also reduces glucagon, a hormone that increases blood sugar levels. Increased insulin and reduced glucagon work in tandem to regulate blood sugar, which helps the body burn body fat more efficiently. In higher doses, semaglutide can decrease hunger and help you feel full longer. This is why users seeking weight loss typically take higher doses than those with diabetes.
As of this writing, three semaglutide medication brands have been FDA-approved: Ozempic, Rybelsus, and Wegovy. All are made by Novo Nordisk, a Danish-based pharmaceutical company that specializes in diabetes medications.
Ozempic is approved for weight loss and diabetes treatment, whereas Rybelsus is only approved for treating type 2 diabetes mellitus. Ozempic is also used to help reduce the risk of heart attack, stroke, or death in patients with heart disease or type 2 diabetes mellitus.
When comparing options, Ozempic and Wegovy are both injected once a week in similar doses. However, Weygovy is the only medication prescribed strictly for weight loss therapy, so Wegovy often has higher dosages to help suppress appetite and increase satiety.
In contrast, Rybelsus is a daily tablet created as an alternative to Ozempic injections to appeal to a broader part of the population. Rybelsus is the only oral GLP-1 receptor agonist available. Although Rybelsus is only approved for type 2 diabetes treatment, it is commonly used for weight loss.
Semaglutide works by mimicking the actions of the GLP-1 glucagon-like peptide-1 (GLP-1) hormone in the body.
At first, semaglutide causes the pancreas to release insulin, which helps regulate blood sugar levels and break down fats. This extra insulin also helps glucose enter cells to be used as energy. In addition to releasing insulin, GLP-1 also reduces the release of glucagon, a hormone that increases blood sugar levels and prevents glucose from entering the bloodstream. By inhibiting those responses, GLP-1 keeps levels in check for diabetics and those trying to lose weight.
In addition to stabilizing blood sugar levels, GLP-1 helps slow down the rate at which food enters the small intestine during digestion. This allows nutrients to be absorbed gradually, which keeps you feeling full longer.
In higher doses, semaglutide can also trigger the brain to suppress appetite and increase satiety. (1) These mechanisms fight hunger and fat, making semaglutide for weight loss highly effective.
To learn more about semaglutide and its possibilities, check out our article: How Much Weight Can You Lose On Semaglutide?
Phentermine is a type of weight loss medication that belongs to the anorectics class, or drugs that suppress appetite.
Phentermine is also referred to as a sympathomimetic amine, meaning it is a central nervous system (CNS) stimulant that triggers neurotransmitter release in the brain. The primary purpose of phentermine is to suppress appetite to treat obesity.
While semaglutide is used to treat other medical conditions, phentermine is used strictly as a weight-loss medication. Phentermine is available as an oral tablet for people struggling with obesity or weight-related health issues. It's meant to be a short-term solution to weight loss, approved for use up to 12 weeks, with regular exercise and calorie restriction.
The FDA approved phentermine in 1959, making it the oldest weight loss medication still available. Phentermine was commonly combined with other weight loss drugs, most notably Fen-Phen, in the 1990s. Fen-Phen was extremely popular for weight loss but was eventually discontinued for its deadly effects on heart valves. The focus then shifted to phentermine hydrochloride (HCl) as a standalone medication.
Due to its close resemblance to amphetamine, phentermine is available today in the United States as schedule IV controlled substance drug under several brand names. Some of the most common brands include Fastin, Acxion, Adipex-P, Duromine, Elvenir, Ionamin, Lomaira, Suprenza, Panbesy, Razin, Redusa, Sentis, and Terfamex.
The key to phentermine for weight loss lies in its ability to trigger our central nervous system and brain. Phentermine is a central nervous system stimulant, increasing the activity of certain neurotransmitters, like norepinephrine, in the brain.
Norepinephrine is responsible for several processes, including our "fight or flight" response and appetite control. While the exact method of appetite suppression is not fully understood, most researchers agree that the increase in norepinephrine, dopamine, and serotonin may suppress appetite in the hypothalamus (the part of the brain that controls hunger).
Norepinephrine binds to the receptors of the hypothalamus, which tricks the brain into feeling fuller and decreases hunger. Elevated dopamine levels help improve overall mood and well-being, which helps motivate people to stick to their diets.
Phentermine is very similar to amphetamines, as they are sympathomimetic amines that affect the same neurotransmitters, mainly dopamine and norepinephrine. Like amphetamines, phentermine can boost energy, which is helpful for weight loss. In addition to appetite suppression, phentermine also stimulates the release of epinephrine, better known as adrenaline, which helps break down stored body fat. (2)
Semaglutide can be used for short- or long-term to promote weight loss, whereas phentermine is meant for short-term use, with a maximum of 12 weeks, so we compared results for similar periods.
A study in Korea measured weight loss from phentermine in 795 obese participants over 12 weeks. The average weight loss was 3.8 kg (8.4 lbs), and more than 45% of participants lost at least 5% of their total body weight. (3)
Anecdotal evidence from the sub-Reddit r/loseit has a post, "Phentermine and weight loss experience," that shares several success stories. User Comfortable-Level-56 shared, "I just finished my 3rd month on phentermine. I have lost 33 pounds and gone down two pant sizes." (source)
A comparable study for semaglutide measured weight loss at three- and six-month intervals in 175 obese patients. After three months, the average weight loss was 6.7 kg (14.7 lbs), or roughly 5.9% of total body weight loss. After six months, the average weight loss was 12.3 kg (27 lbs), equivalent to roughly 10.9% total body weight loss. (4)
Anecdotal evidence from the sub-Reddit r/Semaglutide has a post "Average weight loss" that shares several amazing transformations. Most users agree that you drop several pounds in the first few weeks and then average roughly one pound per week. User Ok_Cow_8235 posted, "In the beginning first two months, I was 4-5 lbs a week, then it slowed down to 1-2 lbs." (source)
Based on results from three months' use, semaglutide is slightly better at weight loss, with an average loss of 14.7 pounds compared to 8.4 lbs with phentermine.
Both medications have potential side effects to monitor as a way to determine if a dose increase is appropriate. If you experience rare side effects, you should contact a healthcare professional.
Phentermine common side effects:
Phentermine rare side effects:
Semaglutide common side effects:
Semaglutide rare side effects:
Semaglutide is widely available in subcutaneous injection and oral tablet form, whereas phentermine is only available orally.
In both Ozempic and Wegovy, semaglutide is a once-weekly injection, which can be done any time, as long as it's the same day of the week. They both start at 0.25 mg for the first month to assess the body's response. From there, users can increase the dose as needed, with a maximum dose of 2.4 and 2 mg, respectively. The most common injection sites are the upper arm, thigh, and stomach, which users rotate each injection.
The oral version of semaglutide, Rybelsus, is a daily tablet with a strict administration protocol. Rybelsus must be taken with water first thing in the morning at the same time every day, 30-60 minutes before eating. Users start Rybelsus at 3mg for the first month, then slowly increase to 7 or 14 mg daily.
Phentermine is available in various oral forms, including a tablet, capsule, or disintegrating tablet, which all have dosing protocols. Oral tablets come in 8 or 37.5 mgs, such as Adipex-P. Both oral capsules and disintegrating tablets come in 15, 30, and 37.5 mg.
Regardless of the brand, users should take the first dose in the morning, one hour before breakfast, or one to two hours after. Users should take their last dose at least 8-10 hours before bedtime due to the stimulant effect.
As far as overall length of medication goes, semaglutide has been proven safe for 68 weeks, so people may benefit from staying on longer. Phentermine, in contrast, is only approved for 12 weeks due to tolerance-building, potential for abuse, and side effects.
Little research exists to determine if you can take semaglutide and phentermine together, leading to lots of mixed opinions.
While there are no interactions between the two drugs, there are also no studies, so we don't know if it's safe. The consensus is that if your healthcare provider approves and your body can handle both medications without side effects, it will be beneficial and increase weight loss.
In the sub-Reddit r/Semaglutide, a post titled "Semaglutide AND Phentermine" has a mix of positive results and overwhelming side effects.
User MandeetheNurse posted, "I haven't had any issues with the combo. So far, in about 4 months, I've lost 48 pounds." (source)
However, user smaldogs shared, "I am on my 3rd week. The second week the lightheadedness really kicked in and then followed the constipation so I'm just wondering what adventures lie ahead." (source)
Each drug works great individually, so ideally users should try to stick to one or the other unless you are struggling to lose weight. Another thing to consider is that phentermine can only be used for 12 weeks, so you can't take both long-term. If you struggle to lose weight with just one medication and can handle the side effects, you may benefit from both.
Avoid taking semaglutide if you have any of the following:
People who should avoid taking phentermine include those with the following:
In case we missed anything, below are the most common questions related to semaglutide and phentermine.
Yes, phentermine is a scheduled IV controlled substance and requires a prescription.
No, semaglutide is not insulin, but it does increase insulin release. The increase in insulin helps lower blood sugar levels and combat fat storage.
Studies show that semaglutide is slightly more effective at weight loss, with an average weight loss of nearly 15 lbs in three months compared to 8.5 lbs in the same time using phentermine. (2) (3)
The exact location of fat loss on the body is highly dependent on genetics and body type, but yes, semaglutide helps reduce belly fat and all body fat.
Some of the reasons you may not be losing weight include too low dosage, not being on a low-calorie diet, having been on long enough, not exercising, using alcohol or drugs, not drinking enough water, dose administration issues, or it's possible you simply do not respond to the drug.
If you struggle with obesity, several weight loss supplements and medications can help transform your body. Of your options, some of the best weight loss medications available are phentermine and semaglutide.
Phentermine is an oral tablet for short-term use that triggers the brain to suppress appetite, break down body fat, and increase energy. Semaglutide comes in either an oral tablet or subcutaneous injection that increases insulin and reduces glucagon to stabilize blood sugar levels, use stored fat for energy, and help suppress appetite.
Both medications have proven effective for sustained weight loss efforts, although semaglutide has a slight edge due to long-term safety. The decision comes down to personal preference, your health status, and a conversation with your healthcare provider.
If you want to learn more about the differences in semaglutide products, check out our article Ozempic vs. Rybelsus: Which One Is Better? If you want to compare semaglutide to another popular fat burner, check out our articles on Liraglutide vs. Semaglutide, Tirzepatide vs Semaglutide, and Semaglutide vs Metformin.
Chao, Ariana M, et al. "Clinical Insight on Semaglutide for Chronic Weight Management in Adults: Patient Selection and Special Considerations." Drug Design, Development and Therapy, vol. Volume 16, Dec. 2022, pp. 4449–4461, https://doi.org/10.2147/dddt.s365416.
Kim, Kyoung Kon, et al. "Effects on Weight Reduction and Safety of Short-Term Phentermine Administration in Korean Obese People." Yonsei Medical Journal, vol. 47, no. 5, 2006, p. 614, https://doi.org/10.3349/ymj.2006.47.5.614.
Kim, Hyun Ok, et al. "Postmarketing Surveillance Study of the Efficacy and Safety of Phentermine in Patients with Obesity." Korean Journal of Family Medicine, vol. 34, no. 5, 2013, p. 298, www.ncbi.nlm.nih.gov/pmc/articles/PMC3791337/, https://doi.org/10.4082/kjfm.2013.34.5.298.
Ghusn, Wissam, et al. "Weight Loss Outcomes Associated with Semaglutide Treatment for Patients with Overweight or Obesity." JAMA Network Open, vol. 5, no. 9, 19 Sept. 2022, p. e2231982, jamanetwork.com/journals/jamanetworkopen/fullarticle/2796491?resultClick=1, https://doi.org/10.1001/jamanetworkopen.2022.31982.
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