New findings on metformin.👀👀👀

Every once in a while, new benefits of metformin are discovered. Earlier this
year, a large cohort study conducted by researchers from the University of Southern Denmark in Denmark and Stanford University in the United States also found new findings on metformin. The study noted that men took metformin in the three months before conception (during sperm development). His male offspring will be more prone to reproductive organ defects at birth. The incidence of severe defects of the genitals or urinary tract was 3.39 times that of the control group. They also found that a man taking metformin for a year before or after the 90 days window period for sperm production did not affect his male offspring. However, it is worth noting that the findings of this study are only preliminary and observational and require further confirmation. Men who are taking metformin do not need to stop taking metformin before trying to conceive. In fact, many reasons for miscarriage are due to problems with men's sperm. It takes about 90 days for sperm to develop, form and finally mature in the epididymis. Therefore, men should also prepare for pregnancy three months in advance to improve the quantity and quality of sperm.

Mechanism of action of metformin.

Metformin reduces postprandial blood glucose levels by delaying intestinal absorption of glucose, increasing GLP-1 levels, reducing peripheral insulin resistance, and increasing muscle tissue uptake and utilization of glucose. It also reduces fasting blood glucose levels by reducing hepatic insulin resistance and reducing hepatic glucose output. The reduction in postprandial blood glucose and fasting blood glucose results in a reduction in HbA1c.

Common adverse reactions of metformin.

Common adverse reactions to metformin are headache, nausea, vomiting, bloating, indigestion, abdominal discomfort, diarrhea and fatigue. Most patients experience adverse reactions within the first 10 weeks of treatment. These adverse reactions generally will be gradually tolerated or disappear with the extension of treatment time. 

Therapeutic dose of metformin.

The minimum recommended dose of metformin is 500 mg per day and the optimal effective dose is 2000 mg per day. The maximum dose for adults in ordinary tablets is 2550 mg per day and the maximum recommended dose in extended-release formulations is 2000 mg per day. Switching to metformin sustained-release preparations, starting with small doses and gradually increasing the dose are all effective ways to reduce the occurrence of adverse reactions. In addition, long-term use of metformin may affect the absorption of vitamin B12, resulting in a decrease in vitamin B12 levels in the patient's body.

Other effects of metformin.

Cardiovascular protection.

Insulin resistance in diabetic and non-diabetic patients is improved by metformin. This reduces basal and post-load insulin levels, which directly and indirectly protects the cardiovascular system.

Improve blood lipid levels.

Fat synthesis and metabolism are improved by metformin. Studies have shown that metformin can significantly reduce triglyceride, LDL-cholesterol and total cholesterol levels in patients with type 2 diabetes, but it did not significantly alter the effect of HDL-cholesterol.

Improve the effect of non-alcoholic fatty liver.

Generally, patients with nonalcoholic fatty liver disease can safely take metformin. Unless the patient has significant hepatic impairment (such as serum transaminases greater than three times the upper limit of normal), hepatic insufficiency, or decompensated cirrhosis.

Treatment of polycystic ovary syndrome.

Polycystic ovary syndrome is a heterogeneous disorder characterized by polycystic ovary morphology, ovarian dysfunction, and hyperandrogenism. Its pathogenesis is unclear. Patients usually have varying degrees of hyperinsulinemia. There is medical evidence that metformin reduces androgen levels, plasma insulin levels and increases estradiol levels. It can improve menstrual regularity, improve hirsutism and induce ovulation in polycystic ovary syndrome patients.

Antitumor effect.

Diabetes may be a risk factor for a variety of tumors, including breast, pancreatic, colorectal, and endometrial cancers. Several studies have shown that metformin inhibits tumor initiation and progression. It reduces the risk of breast, lung, rectal, prostate and other cancers.

Other potential effects of metformin.

Alter gut flora.

A study found that the gut microbiome of patients with type 2 diabetes was favorably changed by metformin.

Reduce the risk of Parkinson's disease in patients with type 2 diabetes.

Metformin promotes the growth of new neurons and repairs damage to the nervous system.

Reversal of left ventricular hypertrophy in non-diabetic patients.

Studies have shown that metformin can improve vascular endothelial cell function, delay myocardial cell apoptosis, inhibit ventricular remodeling, and reduce patient weight. These effects may reverse left ventricular hypertrophy in non-diabetic patients.

Prevent age-related macular degeneration.

A study found that people with type 2 diabetes who took metformin had a significantly lower incidence of age-related macular degeneration. This may be related to the antioxidant and anti-inflammatory functions of metformin.

Reversal of pulmonary fibrosis.

Studies have shown that the use of metformin can re-sensitize myofibroblasts to apoptosis. And in mouse models, metformin can speed up the ablation of already fibrotic tissue.

Promote hair growth.

Studies have found that metformin can stimulate telogen hair follicles to enter the growth phase and promote hair growth in mice.

Reduce the risk of blood clots caused by haze.

There are animal studies showing that inflammation caused by smog is prevented by metformin. It inhibits the formation of arterial blood clots, thereby reducing the risk of cardiovascular disease.

Reduce adverse effects of glucocorticoid therapy.

Some studies have shown that patients treated with glucocorticoids and metformin have the possibility of reversing the adverse effects of glucocorticoids.

Finally, metformin can cause fatal lactic acidosis. Therefore, metformin should be used under the guidance of a doctor or pharmacist. Although new effects of metformin are frequently discovered recently, few of them are certified by medical guidelines.

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What should patients pay attention to when taking aspirin for a long time?📝📝📝

Aspirin is a classic and commonly used antithrombotic drug. In clinical, its application is very extensive. It can be used to prevent and treat cerebral thrombosis, cardiopulmonary infarction, angina pectoris, ischemic heart disease, etc. It plays an important role in the prevention of primary and secondary cardiovascular disease. Therefore, aspirin needs to be taken by many patients for a long time. The best results for these patients can only be achieved by taking aspirin correctly. The following will tell about the correct way to take aspirin.

When is it better to take aspirin?

Is it better for patients to take aspirin in the morning, noon, or evening? Some experts pointed out that there is controversy about the time of taking aspirin in the current research. Studies have shown that platelet activity increases in the morning. Therefore, from six o'clock to twelve o'clock in the morning is the high incidence time of cardiovascular events, so patients are advised to take aspirin in the morning. However, other studies have suggested that patients take aspirin at night to lower their blood pressure better, so they are advised to take it at night. In fact, the mechanism of action of aspirin is that the peak blood levels of the drug are not reached until several hours after taking the drug. Its antiplatelet effect can also last for several days after repeated administration. Therefore, whether aspirin is taken in the morning or in the evening, its antiplatelet effect persists after repeated doses. Therefore, it is generally more important to recommend that patients take aspirin regularly for a long time.

Different dosage forms of aspirin have different doses.

Different dosage forms of aspirin have different effects when taken before or after meals. If a patient is taking aspirin as a regular tablet, this dosage form causes it to be broken down in the stomach. Therefore, this form of aspirin should be taken after meals to reduce its damage to the gastric mucosa. If a patient is taking aspirin as an enteric-coated tablet, it will only dissolve in alkaline intestinal fluids and not in acidic gastric fluids. Taking this form of aspirin after meals can delay its absorption. Moreover, the alkaline content of food may cause the enteric-coated tablet to dissolve in the stomach and cause damage to the gastric mucosa. Therefore, it recommends that enteric-coated tablets should be taken 30 to 60 minutes before meals.

Patients should avoid missing to take aspirin.

Missed doses occasionally occur in patients taking long-term medication. What are the effects of missing an aspirin? Although the activity of existing platelets can be effectively inhibited by a single low-dose aspirin, the human body generates 10-15% of platelets every day. Therefore, patients need to take regular daily aspirin to keep these new platelets suppressed. If the patient occasionally misses an aspirin, it has little effect on the antithrombotic effect. However, frequent missed doses increase the risk of blood clots. It is recommended to take the medicine at a fixed time each day to avoid missed doses. If the patient misses a dose and is close to the next dose, there is no need to make up the dose and do not double the dose to avoid increasing adverse reactions. If the patient misses a dose and it is long before the next dose, make up the dose immediately.

Do not drink alcohol while taking aspirin.

First, the activity of an alcohol metabolizing enzyme (alcohol dehydrogenase) is inhibited by aspirin. It slows the metabolism of alcohol and causes more alcohol to accumulate in the body. Alcohol intoxication can become more likely. In addition, alcohol also increases the risk of gastric mucosa and liver damage. Therefore, alcohol should be avoided while taking aspirin. If the patient must drink alcohol, the patient should separate the medication time and alcohol consumption to reduce the interaction between the two.

Who is more likely to experience gastrointestinal adverse reactions when taking aspirin?

The patient's medication compliance is often affected by the adverse reactions of the medication. If a patient develops stomach pain after taking aspirin, it is easy for them to stop taking the drug. Digestive tract adverse reactions are more likely to occur in patients with a history of smoking and drinking, taking high-dose aspirin, taking anticoagulants at the same time, age > 65 years, or previous history of gastrointestinal diseases. These patients may need to take stomach-protecting drugs to reduce the occurrence of gastrointestinal adverse reactions.

Patients who develop aspirin resistance should be reassessed and adjusted their medication.

Aspirin resistance refers to the inability of patients to prevent blood clots after taking aspirin. When this occurs, the patient needs to be reassessed and assessed for factors that affect the efficacy of aspirin. Such as blood pressure, blood sugar, blood lipids are not effectively controlled. Does the patient take medication regularly? Are there any interactions between other drugs (such as NSAIDs) and aspirin? If the patient does not have the above factors, consider increasing the aspirin dose or switching to other antiplatelet drugs.

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What is the difference between alogliptin, linagliptin, saxagliptin, sitagliptin and vildagliptin?📊📊📊

Dipeptidyl peptidase-4 (DPP-4) inhibitor is a new type of oral hypoglycemic drug with the fastest growing clinical use recently. Alogliptin, linagliptin, saxagliptin, sitagliptin and vildagliptin all belong to this class of drugs, but what exactly is the difference between them?

What is the mechanism of action of DPP-4 inhibitors?

Intestinal cells are stimulated by food (especially carbohydrates) to secrete hormones (such as GIP and GLP-1) that increase insulin secretion. And 70 to 80% of the incretin activity is produced by GLP-1.

DPP-4 in the human body can easily degrade GLP-1. It results in a half-life of GLP-1 in plasma of less than two minutes. Concentrations of endogenous GLP-1 are elevated two to threefold by the efficacy of DPP-4 inhibitors in inhibiting DPP-4. The effects of promoting insulin secretion and inhibiting glucagon secretion of GLP-1 are glucose concentration-dependent. Therefore, DPP-4 inhibitors do not increase the risk of hypoglycemia and are therefore suitable for use in the elderly.

What is the difference in chemical structure between DPP-4 inhibitors?

Alogliptin

Linagliptin

Saxagliptin

Sitagliptin

Vildagliptin

What is the difference between the dosage of DPP-4 inhibitors?

1. Alogliptin: It is a DPP-4 competitive inhibitor. It binds non-covalently to the active site of DPP-4. Therefore, its half-life is relatively long, up to 21 hours. Alogliptin is taken once a day, 25 mg each time.
2. Linagliptin: It is a DPP-4 competitive inhibitor. It binds non-covalently to the active site of DPP-4. Therefore, its half-life is 12 hours. Linagliptin is taken once a day, 5 mg each time.
3. Saxagliptin: It binds covalently to the active site of DPP-4. Therefore, its dissociation and association will be slower. This makes its half-life only 2.5 hours, but its hypoglycemic effect lasts longer. Saxagliptin is taken once a day, 5 mg each time.
4. Sitagliptin: It is a DPP-4 competitive inhibitor. It binds non-covalently to the active site of DPP-4. Therefore, its half-life is about 12 hours. Sitagliptin is taken once a day, 100 mg each time.
5. Vildagliptin: It is also covalently bound to the active site of DPP-4. Its half-life is 3 hours. Vildagliptin is taken twice a day, 50 mg each time.

Food does not affect the absorption of the above DPP-4 inhibitors.

Precautions for use in patients with renal insufficiency.

1. Alogliptin: It is rarely metabolized in the body and its metabolites are also active. Its bioavailability can reach 100%. It rarely interacts with other medicines. About 76% of alogliptin is excreted through the kidneys. Therefore, its dosage should be adjusted when it is used in patients with renal insufficiency.
2. Linagliptin: It is rarely metabolized in the body. Its metabolites are inactive. Its bioavailability is about 30%. It rarely interacts with other medicines. Less than 5% of the administered dose of linagliptin is excreted by the kidneys. Therefore, it does not require dose adjustment when used in patients with renal insufficiency.
3. Saxagliptin: It is metabolized by CYP3A4/5. Its metabolites are active. Its bioavailability is about 67%. It rarely interacts with other medicines. Its usual dose is 5 mg once a day. However, when it is co-administered with potent CYP3A4/5 drugs such as itraconazole, clarithromycin and atazanavir, the dose of saxagliptin should not exceed 2.5 mg per day. About 75% of saxagliptin is excreted through the kidneys. Therefore, its dosage should be adjusted when it is used in patients with renal insufficiency.
4. Sitagliptin: It is rarely metabolized in the body. Its metabolites are inactive. Its bioavailability is about 87%. It rarely interacts with other medicines. About 79% of sitagliptin is excreted by the kidneys. Therefore, its dosage should be adjusted when it is used in patients with renal insufficiency.
5. Vildagliptin: It is not metabolized by CYP enzymes, but inactivated by hydrolysis. Its bioavailability is about 85%. It is less likely to interact with other drugs. About 85% of vildagliptin is excreted through the kidneys. Therefore, its dosage should be adjusted when it is used in patients with renal insufficiency.

What are the common adverse reactions of DPP-4 inhibitors?

It is possible that DPP-4 inhibitors increase GLP-1 levels. This can be associated with delayed gastric emptying and appetite suppression. Therefore, DPP-4 inhibitors can cause stomach upset. Their main adverse reactions are upper respiratory tract infection, nasopharyngitis and headache. Less common adverse reactions are hypersensitivity reactions and angioedema. 

In addition, alogliptin and saxagliptin have the potential to increase the risk of heart failure hospitalization events. Therefore, when a patient has risk factors for heart failure, the patient should be observed for symptoms and signs of heart failure during treatment.

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