Weight Management Revolution? A Look at the Pros and Cons of New Antiobesity Drugs

According to a review in the Journal of Obesity & Metabolic Syndrome, obesity is a growing health problem. Existing weight-loss medications aren't very effective. Two new injectable drugs, semaglutide and tirzepatide, show promise. Studies in people with diabetes suggest they cause significant weight loss, potentially better than older medications. Both improved blood sugar control too. Side effects like nausea exist, but overall, they seem safe. These drugs offer a new weapon in the fight against obesity, potentially helping people lose weight and improve their health.

Key Findings

This review highlights two new injectable drugs, semaglutide and tirzepatide, showing promise for substantial weight loss in obese patients.

The Problem: Obesity rates are climbing globally, leading to a rise in health complications. Existing weight-loss medications only achieve modest results.

New Hope: Semaglutide and tirzepatide are injectable drugs showing significant effectiveness in promoting weight loss, exceeding older medications.

Focus of the Review: This review compares the effectiveness and safety of semaglutide and tirzepatide based on clinical trials involving patients with type 2 diabetes.

Trial Details:

• The trials included are STEP 2, SURPASS-1, and SURPASS-2.

• All participants had type 2 diabetes.

Key Findings:

• Both semaglutide and tirzepatide led to greater weight loss than placebo in these trials.

• Compared to existing medications, these drugs offer potentially superior weight-loss results.

Specific drug comparisons:

• Weight Loss: Studies suggest tirzepatide may be more effective for weight loss than semaglutide, though some uncertainties remain due to differences in trial design and dosage.

• Glycemic Control: Both drugs improved blood sugar control in patients with type 2 diabetes.

• Safety: Both medications were generally well-tolerated, but side effects like nausea and diarrhea were reported.

Overall Significance:

• Semaglutide and tirzepatide represent significant advancements in the fight against obesity.

• These drugs offer patients a potential tool to achieve substantial weight loss, potentially leading to improved health outcomes

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The global prevalence of obesity has undergone a drastic surge since 1975, transcending boundaries of gender, age, and nationality. In 2016 alone, approximately 39% of adults worldwide were overweight, with 13% classified as obese, accounting for a staggering 1.9 billion and 650 million individuals, respectively. This alarming escalation of obesity is not merely a matter of excess body weight but a profound health crisis associated with a myriad of non-communicable diseases, including but not limited to type 2 diabetes mellitus (T2DM), hypertension, cardiovascular diseases, fatty liver disease, and certain cancers.

Pharmacotherapy as a Solution to Combat Obesity

Recognizing the severity of the obesity epidemic, regulatory bodies such as the U.S. Food and Drug Administration (FDA) have approved pharmacotherapy options to complement dietary and lifestyle modifications. Individuals with a body mass index (BMI) of at least 30 kg/m2 or 27 kg/m2 with obesity-related comorbidities like T2DM or hypertension are eligible for such interventions. The advent of anti-obesity medications (AOMs) has ushered in a new era in the treatment of obesity, offering hope to those struggling to achieve sustainable weight loss.

Semaglutide: A Breakthrough in Obesity Treatment

Semaglutide, an analog of human glucagon-like peptide-1 (GLP-1), has emerged as a promising therapeutic option for obesity management. With structural modifications conferring enhanced stability and prolonged half-life, semaglutide offers the convenience of weekly administration. Its mechanism of action involves glucose-dependent insulin secretion, suppression of glucagon release, and modulation of appetite regulation, culminating in reduced food intake and increased satiety.

Efficacy of Semaglutide in Weight Loss

Clinical trials, notably the Semaglutide Treatment Effect in People with Obesity (STEP) trials, have underscored the substantial weight reduction achieved with semaglutide therapy. In the STEP 2 trial targeting obese individuals with T2DM, semaglutide at a dose of 2.4 mg led to a remarkable 9.6% decrease in body weight over a 68-week period. Moreover, semaglutide demonstrated superiority over alternative doses and placebo, solidifying its position as a frontline AOM.

Tirzepatide: A Novel Therapeutic Approach

Tirzepatide, a dual receptor agonist of glucose-dependent insulinotropic polypeptide (GIP) and GLP-1, offers a unique mechanism of action in combating obesity. Through synergistic effects on appetite suppression and energy expenditure, tirzepatide presents a compelling option for individuals resistant to conventional weight loss interventions.

Evaluating the Weight-Loss Efficacy of Tirzepatide

The SURPASS trials have provided compelling evidence of tirzepatide's efficacy in weight reduction among patients with T2DM. Doses of 5 mg, 10 mg, and 15 mg administered weekly demonstrated dose-dependent weight loss, with the highest dose achieving a remarkable 13.1% reduction in body weight. Notably, tirzepatide showcased superiority over semaglutide in certain instances, suggesting its potential as a formidable contender in the realm of AOMs.

Comparative Analysis of Semaglutide and Tirzepatide

Conducting a comparative analysis of semaglutide and tirzepatide is imperative to inform clinical decision-making and optimize treatment outcomes. While both agents exhibit remarkable weight-loss efficacy, subtle differences in their pharmacological profiles and clinical outcomes warrant careful consideration.

Glycemic Control and Safety Profile

Both semaglutide and tirzepatide help people with diabetes control their blood sugar levels (HbA1c). They achieved this improvement without a big jump in effectiveness at higher doses (except for a small difference). The good news is that a high percentage of people were able to reach their target blood sugar goals with these drugs. However, there is a catch. These medications increased the risk of low blood sugar events (hypoglycemia), especially with tirzepatide. The most common side effects were nausea and other digestive problems, which were more frequent with higher doses of tirzepatide compared to semaglutide. In some cases, these side effects were severe enough for people to stop taking the medication, particularly with tirzepatide. Beyond weight loss, assessing the impact of semaglutide and tirzepatide on glycemic control and safety is paramount. Clinical trials have demonstrated the favorable effects of both agents on haemoglobin A1c (HbA1c) levels, with concomitant improvements in cardiovascular risk factors. However, further research is warranted to elucidate the long-term safety and tolerability of these agents, particularly in diverse patient populations.

Glycemic Control

• Both semaglutide and tirzepatide improved blood sugar levels (HbA1c) in people with diabetes.

• The improvement in blood sugar control was similar between the two drugs at most doses. However, there was a small additional improvement with the highest dose of tirzepatide (15 mg) compared to the highest dose of semaglutide (2.4 mg).

Safety

• Adverse Events:

  • Both semaglutide and tirzepatide increased the risk of side effects, but this was more common with the higher doses of each drug.

  • The most common side effects were gastrointestinal problems, such as nausea and diarrhea. These side effects were more common with tirzepatide than semaglutide and were more likely to be severe enough to cause people to stop taking the medication.

  • In some studies, more people taking tirzepatide stopped taking the medication due to side effects compared to those taking semaglutide.

• Hypoglycemia:

  • Both semaglutide and tirzepatide increased the risk of low blood sugar events (hypoglycemia).

  • This risk was especially high with the highest dose of tirzepatide (15 mg).

Overall

• Both semaglutide and tirzepatide are effective for improving blood sugar control in people with diabetes.

• However, tirzepatide is more likely to cause side effects, which may be severe enough to cause people to stop taking the medication.

• More research is needed to see if these drugs are safe and well-tolerated in the long term, especially for different groups of people.

To Summarize

• Blood Sugar Control: Both semaglutide and tirzepatide effectively reduce blood sugar levels (HbA1c) in people with type 2 diabetes. While both drugs achieve significant improvement, tirzepatide might offer a slight advantage at its highest dose (15mg) compared to the highest dose of semaglutide (2.4mg). However, the additional benefit of tirzepatide is relatively small.

• Side Effects: Both medications come with an increased risk of side effects, especially as the dosage increases. The most common side effects are gastrointestinal issues like nausea, diarrhea, and vomiting. However, tirzepatide is more likely to cause these side effects, and they tend to be more severe compared to semaglutide. In some studies, a higher percentage of participants taking tirzepatide discontinued treatment due to side effects compared to those taking semaglutide.

• Low Blood Sugar (Hypoglycemia): Both semaglutide and tirzepatide can increase the risk of experiencing low blood sugar events. This risk is particularly high with the highest dose of tirzepatide (15mg). It's important for people taking these medications to be aware of the signs and symptoms of hypoglycemia and to have a plan for managing it if it occurs.

Conclusion

Despite recognition of the severe medical and socioeconomic burden of obesity, the weight-loss effects of pre-existing AOMs are insufficient to overcome obesity-associated complications. The recently introduced peptides semaglutide and tirzepatide can be administered once weekly and have demonstrated substantially improved weight-losing effects within a tolerable safety margin in a series of STEP and SURPASS trials. These highly effective medications enable a considerable proportion of their users to achieve sufficient weight loss to alleviate obesity-associated metabolic diseases.
References

Jung, H. N., & Jung, C. H. (2022). The Upcoming Weekly Tides (Semaglutide vs. Tirzepatide) against Obesity: STEP or SURPASS?. Journal of obesity & metabolic syndrome, 31(1), 28–36. https://doi.org/10.7570/jomes22012

Related

https://healthnewstrend.com/high-fat-intake-linked-to-obesity-rise-in-china-new-study

https://healthnewstrend.com/obesity-and-cardiometabolic-risk-why-bmi-isnt-enough

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