New material reveals what substances compete with insulin, how the glucose warehouse is run, if weight loss drugs can protect against stroke and cause cancer, and what to do if they are broken down in the blood in just a few minutes.
Many became chefs during quarantine, and all bloggers began writing about food. As a result of inactivity and constant proximity to the refrigerator, many gained at least a few pounds, and some even began to develop health problems due to obesity. While some may be motivated to join sports or cut their diets, others may already be considering weight loss drugs. Furthermore, they treat type 2 diabetes, in which insulin sensitivity is reduced, which is a type of diabetes that develops as people age, particularly those who are overweight. The topic for today is a medicine (a medicine, rather than a miracle fitness tea or other dietary supplement) called Saxenda, which has been used for these indications for quite some time.
Where does this come from?
Liraglutide is the active substance that helps regulate glucose in the body. Chemically, it is a glucagon-like peptide-1, a short sequence of amino acids related to glucagon. Glucagon is a peptide hormone produced by cells in the pancreas called the islets of Langerhans. It works by regulating fatty acids and blood sugar by opposing insulin, which stores glucose in cells. When blood sugar levels decrease or demand increases, glucagon acts to release glucose.
Glucagon-like peptide-1 (GLP-1) is derived from the same precursor substance as glucagon. After the pancreas has finished producing glucagon and other peptides, the substance converts into GLP-1 in the brain and intestines. The result is two substances with similar roots that serve different functions in regulating glucose in the body.
It is registered under the brand names Victoza and Saxenda for subcutaneous administration. If it is not injected, the digestive system would split it back up into “bricks” – amino acids, which are not effective individually as the whole peptide.
The inconvenience and high cost are offset by a direct action: the drug enters the bloodstream rapidly. However, if doctors used GLP-1 directly, every second molecule would be broken down within 30 minutes of intramuscular injection and within a few minutes of intravenous administration. Since blood glucose equilibrium is very fragile, it is maintained by several mechanisms that counteract each other from different sides. To prevent excess GLP-1 from going too far in arbitrariness, special proteins rush to break it down. However, this is problematic for medicines. In the case of a large dose, the action would be too sharp, causing the person to lose consciousness due to a decrease in blood sugar (by the way, you can’t administer a double dose of liraglutide if you miss one dose), while in the case of small doses, the injection would be too frequent. Therefore, scientists made a slight modification to it so that liraglutide clings to albumin (blood plasma protein) and travels through tissues and blood vessels, releasing it gradually. By doing so, liraglutide can be extended to 13 hours (after this time, half of its molecules in blood plasma will be split). These data, are almost the same for adolescents.
Risks of cancer and other diseases
The fact that a drug has a working mechanism of action does not negate the need to test it on humans in specially designed studies. Firstly, safety is important for a drug, and since GLP-1 at the head of the glucose warehouse becomes influential, like the Italian mafia, a participant in many processes in different organs and tissues, an eye and an eye is needed. It is equally important that the drug performs its functions while also improving the health of the patient, whether he has diabetes or obesity.
PubMed contains almost 200 articles describing double-blind controlled studies on the safety and efficacy of the drug.
Among the side effects that are directly related to the action of the drug is the sharp drop in blood glucose levels (as a result of an overdose or the use of the drug by someone without diabetes), which can lead to a drop in blood pressure and loss of consciousness due to hypoglycemia. Dizziness is also a possibility.
Furthermore, liraglutide can cause gastrointestinal discomfort, including nausea, indigestion, diarrhea, and constipation. Consequently, these conclusions led researchers to compare the drug with analogs that had a similar chemical structure and a placebo (such as this study). The majority of side effects come from here according to study on obese children. Patients (out of 135 participants) complained about them at almost the same frequency as those taking placebo, but the frequency was higher among those taking liraglutide. Such side effects occur in five percent of patients on average.
The drug is well tolerated in patients with steatohepatitis (liver damage), and it even reduces the risk of heart attacks, strokes, and premature death among those with diabetes. It did not, however, help people with reduced left ventricular ejection fraction of the heart correct the problem, and also threatened to cause dangerous side effects for the heart and blood vessels in participants with heart failure, which is why further research is needed in this area.
Many of these studies were funded by drug manufacturers, so they must be viewed with caution, since the authors could have a financial incentive to not include every side effect.
However, there are also controversial findings about other dangerous effects of taking the drug. Thus, studies on rats have shown that animals may develop thyroid cancer if they receive liraglutide eight times as much as humans do. However, this has not yet been clarified in the public sphere. There is a risk of thyroid cancer of 0.3 for every 1,000 patients multiplied by the number of years of use, according to the US Food and Drug Administration (FDA). Although fewer people participated, there were more predisposed individuals in the drug group than those in the control group (four out of five versus one out of five).
A concern has been raised by the European Medicines Agency and the FDA about the potential for pancreatic cancer and pancreatitis in patients who take liraglutide. A review of 25 clinical trials involving more than 14 thousand patients has not yet given a clear picture of the risks, so for now, liraglutide remains a suspect.
(Not) appearing in the lists
What do we know about the effectiveness of the drug? In many studies, liraglutide injections daily help people lose weight. The study found that 422 patients lost 6% of their weight in 56 weeks, and most of them maintained their weight after stopping the drug treatment by five or more percent. According to the study, their initial body mass index was 27 kilograms/m2 (with complications) or 30 kilograms/m2.
It was reported in another study of 3,731 participants that the liraglutide group lost 5.6 kg more than the placebo group over 26 weeks, and 15 kilograms was achieved by the most fortunate. Other trials have found that this effect varies with dosage: with daily injections of 1.2 mg, patients lose 4.8 kg on average in 20 weeks (slightly more than Orlistat, a competitor), while with 3.0 mg, patients lose up to 7.2 kg. The majority of studies demonstrated persistence of results through 84 weeks of follow-up, although exercise and diet contributed to this outcome in patients, and again there is a funding conflict.
The effect of GLP-1 and derivative medications has also been proven beyond doubt against diabetes, according to a review on the Cochrane Collaboration website examining nearly 7,000 trials. According to the authors, drugs in this group cause the greatest weight loss, as well as less often causing blood glucose to drop to dangerous levels than other diabetes drugs.
Scientists, however, doubt that such drugs can prevent type 2 diabetes. Liraglutide has not yet been proven to reduce non-insulin-dependent diabetes risk, even though a number of studies have shown that it lowers blood levels of certain precursor substances. The long-term effects of the drug on blood pressure in obese patients are also largely unknown.
Because the drug is available by prescription, self-medication shouldn’t be a problem. This is the right thing to do: an increased dosage can lead to dangerous blood sugar levels (this is known as hypoglycemia), leading to fainting or worse. No one canceled the risks associated with an improper injection. A patient is unlikely to experience anything serious: the most common side effects, which occur in about 5% of patients, will not be dangerous, but rather unpleasant, such as nausea or constipation.
In patients with a body mass index over 30, the drug is recommended (or above 27, but with complications). Taking it for the sole purpose of losing a few pounds, moreover if you do not have type 2 diabetes, is not a good idea. However, if your body weight is 90 kg and you are 165 cm tall, such indicators can already be considered justified. Taking this drug will actually help you lose about 6% of your body weight, which is more than most other weight loss medications.
It has been suspected that the drug increases the risk of thyroid and pancreatic cancer, as well as pancreatitis and heart problems, but these suspicions have only been indirectly confirmed.
Those with impaired kidney and liver functions, pancreatitis, gallbladder disease, and suicidal tendencies (this isn’t a fully proven effect, but better to be cautious) should not use Saxenda. The safety for the child during pregnancy and breastfeeding has not been proven, so it is better not to risk it. It is not recommended for patients with palpitations at rest.
You should consult your doctor before combining this drug with other diabetes drugs: it can enhance the effect of some, interfere with others, so be very careful. Warfarin and other derivatives of coumarin should be used with caution.
Also, don’t forget to maintain a healthy lifestyle: the drug can be a good addition to a calorie-deficient diet and physical activity, but without them, you won’t achieve the results you want.
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