Being overweight is more than just a few extra kilos. It's a chronic condition that affects millions of people around the world. A high BMI is associated with serious health problems, even though it's possible to be obese and healthy. Over sixty chronic conditions, including heart disease, stroke, cancer, and type 2 diabetes, have been linked with obesity. In the United States, obesity rates are also disproportionately affected by geography and ethnicity. This can have generational consequences, as children from overweight families are at a higher risk of becoming overweight themselves.

Some people are predisposed to obesity due to genetics, lifestyle, or biology. Many people report that they struggle to lose weight and keep it off even after modifying their diets and increasing their exercise. In previous articles in this series, we have described how our body stores and responds to energy. This is something that is mostly out of our control. In particular, the gut-brain connection has been implicated as a major factor in determining our appetite and cravings.

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People with high BMIs are not to blame for being unmotivated to lose weight. Some people can't lose weight no matter how much they exercise or eat vegetables. Even when you are doing everything right, the body will resist weight loss. It does this by activating counter-mechanics, which increase cravings.

Recent studies show that pharmaceutical interventions, combined with diet and physical activity, can help enhance weight loss. Millions of people who struggle to reach a healthy weight could benefit from medications that promote weight loss. In the past, doctors were discouraged from prescribing weight-loss medications due to the stigma attached to treating obesity as a medical condition.

A new generation of weight-loss drugs targeting the gut and brain weight-regulating systems promises to help people not only lose weight but also reverse other complications, including diabetes. These medications work because they are based on the idea that signals sent by the gut to the brain can either increase or decrease appetite. It is easier to control eating habits and curb cravings by hijacking the brain-gut communication system. Weight-loss medications, which offer similar benefits to bariatric surgeries without the recovery time and with no side effects, are expected to grow into a $50 billion industry within the next 10 years.

The excitement is building for a drug that will be approved by the FDA for weight loss this year. Produced by Eli Lilly and having the dual action of lowering body weight while normalizing blood sugar, tirzepatide is a drug that has gained FDA approval for weight loss. It is a weekly injection that, in combination with diet and physical activity, can promote weight loss.

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Jastreboff et al.  reported that tirzepatide caused substantial and sustainable weight loss without any side effects. Over 2500 adults who had a BMI that was measurably higher than normal received weekly doses of 5mg, 10mg, and 15 mg of tirzepatide or a placebo. All volunteers participated in lifestyle counseling that included regular sessions encouraging exercise and a healthy diet.

The weight loss of those who received tirzepatide was greater than that of the placebo group. This difference was dose-dependent. Participants who received weekly 15-mg injections saw a weight reduction of 20%, whereas those in the control group experienced a 3% change. This is because many other FDA-approved drugs that treat obesity only enhance weight loss by 3.0 to 8.6%.

Jastreboff et al.  found even more impressive results when they looked at the change in body fat. Participants in all groups treated with tirzepatide lost on average 33.9% more fat than those in the placebo group. This treatment is much more effective than just diet and exercise.

Tirzepatide's benefits go beyond weight loss. Nearly all participants who were prediabetic when the trial began had normal glycemic values by the end of week 72. This was true for all three groups. This means that the future risk of chronic kidney disease and cardiovascular disease, as well as fatty liver disease, is significantly reduced. Only 62% of the placebo group experienced similar results.

Is it safe to use? Yes. Only 6.3% of participants reported serious side effects. This percentage was the same for both treatment and placebo groups. Unsurprisingly, a large portion of both theese side effects were cgroups. y Covid-19 infections which occurred independent from the study. The most common side effects were mild gastrointestinal symptoms suchCOVID-19rinfections,ipation and nausindependentlyoofnd co. Al found that increasing dosage did not necessarily increase the constipation,cts. Both the 10-mg coworkerse 15mg groups experienced similar adverse effects, but 15mg showed a significantly greater weight reduction. This indicates that tirzepatide can be taken in higher doses to maximize its effectiveness.

This 72-week study allowed for many participants to reach or be near a plateau in their weight, which indicates that the drug's benefits can last. Participants in this study agreed to be monitored for two years to evaluate the benefits of this treatment.

What is the mechanism of action? The injection targets the hormone system that regulates weight in the gut. Tirzepatide uses a dual-pronged strategy to detect glucose and regulate energy levels. This medication, which was previously approved by the FDA to treat type-2 diabetes symptoms, has been shown to work by binding to receptors called long-acting GLP-1 receptors. These receptors are activated, which stimulates insulin production. Insulin lowers blood glucose and sends signals to the brain that limit food intake. In the gut, food is also slowed down in both the stomach and the intestines. The feeling of fullness lasts longer and occurs more quickly, which helps to prevent overeating.

Tirzepatide also binds to receptors normally targeted by insulinotropic polypeptides (GIPs) that are glucose-dependent. These nutrient-sensing insulin receptors also mediate eating and appetite in the brain. The activation of GIP receptors in both the brain and fat tissue regulates how calories are stored and consumed in the body. Researchers believe that tirzepatide's weight-loss properties are due to its ability to target both GIP receptors and GLP-1.



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