Dr. Ahmed
Rybelsus and phentermine/ Topiramate (Qsymia) are two oral medicines that have got FDA approval for two separate indications – Diabetes and Obesity.
Rybelsus is the oral formulation of Semaglutide. It has been approved by the FDA for the treatment of diabetes as monotherapy or in combination with metformin or other diabetes drugs.
Phentermine/ Topiramate (Qsymia) is an FDA-approved weight loss medicine. It has no direct effects on blood glucose.
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Can You Take Phentermine and Semaglutide Together?
Rybelsus is oral Semaglutide. Although it has not been approved for weight loss, it is associated with significant weight loss. In fact, higher dose formulations of up to 50 mg per day of Rybelsus are currently being studied for the management of obesity in non-diabetic individuals.
Phentermine/ Topiramate available by the brand name Qsymia is only approved for the treatment of obesity.
Since both drugs are associated with significant weight loss, it is logical that combining Rybelsus and Phentermine/ Topiramate will result in rapid and sustained weight loss.
Since Rybelsus is not approved for use in non-diabetic patients, its weight-loss effects have mostly been studied in obese individuals with diabetes.
When used in diabetic patients, Rybelsus resulted in clinically significant weight loss compared to placebo in doses of 7 mg and 14 mg.
| Baseline Weight | Weight after 26 weeks | Mean Weight Loss | |
| Placebo | 88.6 | 87.2 | -1.4 kgs |
| Rybelsus 7 mg | 89 | 86.7 | -2.3 kgs |
| Rybelsus 14 mg | 88.1 | 84.4 | -3.7 kgs |
Rybelsus monotherapy compared to placebo resulted in significant weight loss after 26 weeks.
Compared to the placebo, there was a mean difference in weight loss of 2.3 kgs after 26 weeks.
Phentermine/ Topiramate, unlike Rybelsus, is only approved for the treatment of obesity in diabetic and non-diabetic individuals.
In nondiabetic individuals, Qsymia in a dose of 15/92 mg has been associated with weight loss exceeding 5% and 10% in 67% and 47% of the individuals.
In individuals with diabetes or other weight-related complications, Phentermine/ Topiramate (Qsymia) has been associated with a weight loss of 70% (>5% or more weight loss) and 48% (10% or more weight loss) when administered in a dose of 15/92 mg per day.
Thus, it is logical to use Rybelsus and Phentermine/ Topiramate in obese diabetic individuals where both drugs have been approved.
However, like metformin, Rybelsus can also be used off-label with phentermine/ topiramate for the treatment of obesity in non-diabetic individuals.
Compared to metformin, Rybelsus is associated with greater weight loss. The weight loss effects of Rybelsus have been comparable to Jardiance (Empagliflozin) and Liraglutide (Victoza and Saxenda) and are superior to Januvia (Sitagliptin).
The weight loss effects of Rybelsus were compared with Sitagliptin (Januvia). Rybelsus in a dose of 7 mg and 14 mg resulted in significantly greater weight loss compared to Sitagliptin 100 mg.
| Baseline Weight | Weight after 26 weeks | Mean weight loss | |
| Sitagliptin 100 mg | 90.9 | 90.3 | -0.6 kgs |
| Rybelsus 7 mg | 91.3 | 89.1 | -2.2 kgs |
| Rybelsus 14 mg | 91.2 | 88.1 | -3.1 kgs |
The mean weight loss in the Rybelsus groups was significantly greater compared to Sitagliptin (Januvia).
Compared to Januvia, there was a mean of -1.6 kgs and -2.5 kgs greater weight loss in the Rybelsus 7 mg and 14 mg groups respectively.
Rybelsus in a dose of 14 mg was compared with Liraglutide in a dose of 1.8 mg. Significant weight loss was observed after 26 weeks in the Liraglutide and Rybelsus groups compared to the placebo.
| Baseline Weight | Weight after 26 weeks | Mean weight loss | |
| Placebo | 93.2 | 92.7 | -0.5 kgs |
| Liraglutide 1.8 mg | 95.5 | 92.4 | -3.1 kgs |
| Rybelsus 14 mg | 92.9 | 88.5 | -4.4 kgs |
The mean weight loss was significant in the liraglutide and Rybelsus groups compared with the placebo medicine.
It can be observed here, that Rybelsus, although not FDA-approved for weight loss in non-diabetic patients, it seems superior to Liraglutide (an FDA-approved weight-loss drug).
Furthermore, Rybelsus is available as an oral pill. Thus, it may be preferred to Liraglutide which is an injectable medicine.
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How Much Weight Loss Is Expected with Rybelsus and Phentermine/ Topiramate Together?
Rybelsus has been associated with a weight loss of about 4 kgs over 6 months. Phentermine/ Topiramate (Qsymia) use has resulted in a weight loss ranging from 3 to 7 kgs over 6 months to one year.
It is expected that Rybelsus and Phentermine/ Topiramate together may cause a weight loss of 8 to 10 kgs (17 to 22) over 6 months to one year.
This much weight loss has only been seen with Wegovy and Tirzepatide (Mounjaro). It is interesting to note that Wegovy is the same drug as Rybelsus except that Rybelsus is given orally while Wegovy is administered into the skin.
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Side effects of combining Rybelsus and Phentermine/ Topiramate:
Rybelsus is associated with gastrointestinal side effects. Patients feel full all the time and may develop severe constipation (or diarrhea). Abdominal pain, nausea, and bloating are common side effects of Rybelsus.
Phentermine is a stimulant drug. It is contraindicated in patients with angina or heart diseases. It is also associated with significant neuropsychiatric side effects.
Common side effects of Phentermine/ Topiramate (Qsymia) include:
- Fatigue and getting tired easily
- Lethargy
- Numbness and tingling sensations
- Lack of focus and concentration
- Palpitations and apprehension
- Impaired sleep and thought processes
- Impaired coordination
- Abnormal bowel habits especially constipation [Ref]
Side effects that are common with both Rybelsus and Phentermine/ Topiramate include gastrointestinal side effects, palpitations, and depression.
It is important to watch for neuropsychiatric symptoms, especially suicidal ideation. Loss of appetite may make the patient intolerant to the combination of these drugs.
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In Summary:
Rybelsus and Phentermine/ Topiramate (Qsymia) may be used in combination as both drugs are associated with significant weight loss. The combination may multiply the weight loss results.
However, it is important to watch for the side effects as the risk of GI-related and neurological side effects may also increase significantly.
