From the Guidelines
It is not common for Ozempic (semaglutide) to completely stop working for appetite suppression and weight loss at the highest dose (2.4 mg weekly), but some patients may experience a plateau effect over time, as seen in the STEP trials where mean weight loss at 68 weeks was 14.9% and 16.0% in the STEP 1 and STEP 3 trials, respectively 1. This phenomenon, known as tachyphylaxis, can occur where the body develops tolerance to the medication, resulting in diminished effectiveness despite dose increases. If this happens, several strategies may help:
- taking a brief "drug holiday" of 2-4 weeks before resuming treatment,
- combining Ozempic with other weight management approaches like dietary changes or increased physical activity,
- or discussing with your healthcare provider about adding or switching to a different medication class, such as tirzepatide, which has been shown to have a dose-dependent weight-loss benefit in the SURMOUNT-1 trial 1. The plateau effect occurs because GLP-1 receptors that semaglutide targets may become less responsive over time, or because the body activates compensatory mechanisms to maintain energy balance. Most patients continue to see benefits at the maximum dose, but individual responses vary based on genetics, metabolism, and lifestyle factors. If you notice decreased effectiveness, consult your healthcare provider rather than adjusting dosage independently, as they can help determine the best course of action, including potentially switching to a different medication, such as liraglutide, which has been shown to be effective in weight loss in several studies, including the one published in the Journal Gastroenterology 1.
From the Research
Ozempic and Appetite Suppression
- Ozempic, also known as semaglutide, is a medication used for weight management and has been shown to be effective in reducing body weight and improving cardiometabolic risk factors 2, 3.
- The medication works by mimicking the action of a natural hormone in the body that helps to regulate appetite and food intake.
- Studies have demonstrated that semaglutide can produce significant weight loss, with an average weight loss of 15% at 1 year 4.
Efficacy of Ozempic at Highest Dose
- The highest dose of semaglutide, 2.4 mg, has been shown to be effective in producing significant weight loss in clinical trials 2, 3.
- In a study comparing semaglutide to liraglutide, another medication used for weight management, semaglutide was found to produce greater weight loss at 68 weeks 3.
- The mean weight change from baseline was -15.8% with semaglutide vs -6.4% with liraglutide, with a difference of -9.4 percentage points (95% CI, -12.0 to -6.8; P < .001) 3.
Potential for Reduced Efficacy Over Time
- There is limited information available on the potential for Ozempic to stop working on appetite suppression and weight loss at the highest dose.
- However, studies have shown that semaglutide can produce sustained weight loss over a period of 68 weeks, with significant improvements in cardiometabolic risk factors and participant-reported physical functioning 2, 3.
- Further research is needed to determine the long-term efficacy of semaglutide and the potential for reduced efficacy over time.