Volume 14 · Issue Z1 · 2022

Semaglutide is a new long-acting glucagon-like peptide-1 receptor agonist (GLP-1RA). Compared with traditional GLP-1RA, the half-life is extended to 7 days. The author reviews the molecular structure and mechanism of action, hypoglycemic, cardiovascular protective effects, weight loss, renal protective effects, and therapeutic progress in non-alcoholic fatty liver disease and neurodegenerative diseases. In addition to the significant effects of lowering glucose and weight loss, semaglutide can also achieve cardiovascular and cerebrovascular protection from many aspects, including protecting vascular endothelium, lowering blood pressure, improving blood lipids, reducing inflammation, improving microcirculation, etc., and is well tolerated. At the same time, semaglutide can also reduce albuminuria, protect the kidney, and reduce the risk of renal composite endpoint events in patients with type 2 diabetes, and can be used for the prevention and treatment of diabetic nephropathy. Semaglutide also has the role of improving insulin resistance in the liver and brain, protecting the liver, reducing the fat content in the liver, improving cognitive ability and protecting nerves. It is also a treatment option for non-alcoholic fatty liver disease and neurodegenerative diseases.

The increasing incidence of diabetes has become a worldwide public health problem. More than 60% of diabetic patients die from cardiovascular disease. In order to reduce related risks, the treatment concept of diabetes is constantly changing. Glucagon-like peptide-1 receptor agonist (GLP-1RA) has a significant effect on improving cardiovascular outcomes in diabetic patients in addition to its significant effects in lowering glucose. The author reviews the application of GLP-1RA liraglutide in diabetic patients, its cardioprotective and renal effects and other benefits. Liraglutide hypoglycemic therapy is both effective and safe, and it also has obvious weight loss advantages, and its therapeutic status has been continuously improved in major guidelines.

Blood glucose monitoring is an important part of diabetes management. 1,5-Anhydroglucitol (1,5-AG) is an indicator that can better reflect the average blood glucose level 1~2 weeks before detection. It has a good application prospect in the screening, diagnosis and prediction of chronic complications of diabetes mellitus. The author reviewed the detection methods, limitations and clinical significance of 1,5-AG. 1,5-AG is another index that can better reflect the abnormal glucose metabolism after blood glucose, urine glucose, glycosylated hemoglobin and glycosylated albumin. 1,5-AG can make up for the shortcomings of traditional detection indexes to a certain extent, and its in-depth biological significance and clinical value need to be confirmed by further research and more evidence-based medical evidence.

Glucagon-like peptide-1 is a polypeptide secreted by small intestinal L cells, which can increase the synthesis and secretion of insulin, suppress appetite, delay gastric emptying, and have other functions in human body besides controlling blood sugar. Glucagon-like peptide-1 receptor agonist (GLP-1RA) has a good effect of lowering blood sugar and glycosylated hemoglobin, lowering body weight and improving insulin resistance, and has a low risk of hypoglycemia, which can improve insulin resistance, protect β cell function and significantly reduce visceral fat. In addition to improving metabolism, it can also have direct and indirect effects on myocardial infarction, heart failure, blood pressure and heart rate in the cardiovascular system. The author reviewed the effect of GLP-1RA on the cardiovascular system, and focused on the evidence of the effect of liraglutide.

Cardiovascular disease is the leading cause of death in diabetic patients in China. With the increasing evidence of cardiovascular outcome trials, the diabetes management pathway guidance of major guidelines began to shift from hypoglycemic to individualized treatment, where priority is given to patients with cardiovascular disease. For patients with atherosclerotic cardiovascular disease (ASCVD), it is recommended to use glucagon-like peptide-1 receptor agonist (GLP-1RA) with cardiovascular benefits, which takes into account both hypoglycemic and cardiovascular outcomes. Semaglutide is the first and only weekly preparation of GLP-1RA with cardiovascular indications in China. It can not only effectively reduce sugar, but also significantly reduce weight, reduce blood pressure, improve blood lipid profile, and reduce the risk of major cardiovascular adverse events, thereby improving patient compliance and quality of life.

Pyroptosis is a form of inflammatory programmed cell death. Inflammasomes are activated, and then mediate the activation of the downstream mediator Caspase family, and finally command pyroporin D (GSDMD) to perform the punching effect, which is an indispensable link in the process of pyroptosis. Pyroptosis plays an important role in the occurrence and development of diabetic nephropathy. The author reviewed the inflammasome NLRP3, Caspase family, GSDMD and related effective drugs, in order to provide new ideas for clinical treatment of diabetic nephropathy. However, the research on the role and significance of cell death induced by pyroptosis in the occurrence and development of diabetic nephropathy is still in the experimental stage. It is necessary to conduct extensive research to further explore the specific mechanism and potential role of cell death induced by pyroptosis and inflammasome in the occurrence and development of diabetic nephropathy.

Type 2 diabetes mellitus (T2DM) is a common clinical chronic disease, which seriously affects the quality of life of patients and shortens the life expectancy of patients. With the emergence of more and more evidence-based medical evidence, the concept of diabetes treatment is constantly changing, from strengthening hypoglycemia to taking into account individual differences, and then emphasizing comprehensive management of metabolic multifactors. Glucagon-like peptide-1 receptor agonist (GLP-1RA) drugs are also becoming more and more important in the guidelines. The author mainly discusses the latest long-acting GLP-1RA semaglutide listed in my country based on work practice. The clinical application efficacy and multiple benefits of peptide. In addition to powerful hypoglycemia, semaglutide also has the effects of cardiovascular protection, kidney protection, weight loss and improvement of abnormal lipid metabolism, and the risk of hypoglycemia is low. In clinical work, the author also has a deep understanding of this. The application of semaglutide in China is still short, and it is necessary to accumulate more clinical experience and conduct research on the mechanism.

Diabetic nephropathy is one of the main complications of diabetes and the main cause of end-stage kidney disease. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are currently widely used in the treatment of patients with type 2 diabetes. A series of basic experimental results show that GLP-1RA can exert renal protective effects independent of hypoglycemic effects by inhibiting oxidative stress, inflammatory response, alleviating renal endothelial dysfunction and promoting urinary sodium excretion. Combination therapy of GLP-1RA with sodium-glucose cotransporter 2 inhibitors may also produce renal protective synergy, providing more choices for clinical medication in patients with diabetic nephropathy.

Sixty obese patients with hyperinsulinemia who attended Zhengzhou Hospital of Traditional Chinese Medicine from May 2021 to May 2022 were selected. According to the random number table method and the order of patients' enrollment, the patients were divided into an experimental group and a control group, with 30 cases in each group. The control group was given pioglitazone and metformin tablets (1 tablet, 2 times/d) oral treatment based on diet and exercise therapy. Based on diet and exercise therapy, the experimental group was treated with subcutaneous injection of semaglutide (0.25 mg, once/week) + pioglitazone metformin tablets (1 tablet, twice/day) orally. The subcutaneous dose was adjusted according to the fasting blood glucose level and gastrointestinal reaction status of the patient. After 1 week of medication, the patient did not experience hypoglycemia and gastrointestinal reaction intolerance, and the subcutaneous dose was adjusted to (0.5 mg, once/week). The comprehensive treatment effect of the two groups was analyzed and observed. It was found that the effective rate of the experimental group was 93.3% (28/30), which was better than that of the control group (63.3% (19/30), and the difference was statistically significant (χ²=11.61，P=0.009）。 The results of this study show that the combination of semaglutide and pioglitazone metformin tablets in the treatment of obesity complicated with hyperinsulinemia has obvious effect, the treatment plan is safe and the weight loss effect is remarkable, and it is a good treatment choice.

Middle-aged male patients. The main reason was "found to have increased blood sugar for 5 years and poor blood sugar control for half a year" and admitted to hospital. He has a history of coronary heart disease and old myocardial infarction for 4 years, a history of hypertension for 4 years, and a history of smoking and drinking. The admission diagnosis was type 2 diabetes mellitus with retinopathy, lower extremity arteriosclerosis obliterans, coronary heart disease, old myocardial infarction, post-coronary stenting status, cardiac function grade I (NYHA grade), hypertension grade 3 (very high risk), obesity, fatty liver. Comprehensive treatment such as lifestyle intervention, hypoglycemic, hypertensive, lipid-lowering, anti-platelet aggregation, circulation improvement and nerve nourishment were given. Metformin sustained-release tablets 1.0 g (twice/d), semaglutide 0.5 mg (once/week), dapagliflozin 10 mg (once/d) combined with hypoglycemic therapy, fasting blood glucose was controlled at about 6 mmol/L, and blood glucose was 7-8 mmol/L 2 hours after prandial. After 3 months, the glycosylated hemoglobin was reexamined at 6.5%, and the body weight was reduced by 7 kg.

The course of treatment with semaglutide was retrospectively analyzed and the literature was reviewed in a patient with type 2 diabetes in the Second Affiliated Hospital of Suzhou University. The patient was a 38-year-old male who was admitted to hospital due to "dry mouth, poly-drinking for more than 6 years, aggravated for 1 week". Insulin pump combined with oral hypoglycemic drugs was given. After blood glucose control stabilized, the gradual simplified regimen was semaglutide 0.5 mg, once/week, insulin deglucin 16 U, once/d, metformin 1 g, twice/d, dapagliflozin 10 mg, once/d, and blood glucose control was good. In addition to lowering glucose, semaglutide can also reduce weight, blood pressure, improve blood lipids, and reduce the risk of cardiovascular events. Moreover, it is convenient to be injected once a week, improves patient compliance, is suitable as a means of long-term treatment, and is helpful to achieve long-term stable control of blood sugar.

A patient with type 2 diabetes mellitus complicated with Down syndrome was diagnosed and treated with insulin combined with liraglutide and dapagliflozin to control blood glucose in Chongqing Seventh People's Hospital. Patient, male, 41 years old. He was admitted to hospital for polydipsia, polydipsia and polyuria for 4 years, increased creatinine for 3 years and increased nocturia for 1 week. Down syndrome was diagnosed at an early age and diabetic nephropathy 3 years ago. One week before admission, the patient had increased nocturia with paroxysmal dizziness and discomfort without obvious trigger, and the blood glucose level was significantly higher than the target value. From the perspective of safety and efficacy, the patient's hypoglycemic treatment regimen was adjusted. On the first day of admission, insulin combined with dapagliflozin 10 mg (once/d) to reduce glycemic acid was started, and liraglutide 0.6 mg (once/d) subcutaneous injection was added on the third day after unsatisfactory effect. After 7 days of admission, the fasting blood glucose was 5.0 mmol/L, and the blood glucose fluctuated from 5.6 to 6.5 mmol/L at 2 hours after meal. There was no hypoglycemia, and the symptoms of nocturia and paroxysmal dizziness were significantly improved. Liraglutide combined with dapagliflozin can protect heart and kidney function, effectively control glucose, reduce the risk of hypoglycemia, and delay the progression of diabetes-related complications.

A case of newly diagnosed type 2 diabetes mellitus was treated with insulin pump combined with liraglutide for intensive hypoglycemic therapy in the Department of Endocrinology of Cixi People's Hospital of Zhejiang Province. The patient was a young male who saw the doctor for "polydipsia, polyuria, and 1 month of emaciation". All examinations were completed after admission, body mass index 34.08 kg/m²Fasting blood glucose was 18.4 mmol/L, glycosylated hemoglobin was 11.3%, diabetes-related triple antibodies were not abnormal, corticotropin-cortisol series tests were not abnormal, and the diagnosis was type 2 diabetes, hyperlipidemia, fatty liver, hepatic insufficiency, and hyperuricemia. After admission, the patient was given continuous subcutaneous injection of insulin pump with a total dose of 20 U before meals and a total basal dose of 22 U, combined with liraglutide 0.6 mg (once/d) subcutaneously. After 3 days of intensive treatment, the patient's blood glucose was controlled within the target range. After 1 week of intensive treatment, the insulin pump was withdrawn, and the dose of liraglutide was adjusted to 1.2 mg (once/d) subcutaneously, combined with metformin 0.5 g (twice/d). The patient's blood glucose was stable, and there was no obvious gastrointestinal adverse reaction. He was discharged for outpatient follow-up. After 3 months of follow-up, the patient's fasting blood glucose ranged from 5.0 to 6.0 mmol/L, 2 h postprandial blood glucose ranged from 5.0 to 8.0 mmol/L, weight loss was 11.5 kg, and glycosylated hemoglobin was 6.1%.

A patient with type 2 diabetes mellitus (T2DM) who was treated in the Department of Endocrinology and Metabolism of Qiandongnan Prefecture People's Hospital of Guizhou Province and had long-term poor blood glucose control combined with arteriosclerotic cardiovascular disease (ASCVD) was retrospectively analyzed. The diagnosis and treatment process of effective blood glucose control with semaglutide optimized hypoglycemic regimen was reviewed and the literature was reviewed. The patient was a 59-year-old male who was admitted to the hospital because "blood sugar was found to be elevated for more than 10 years and blood sugar control was poor for more than 2 months" and was definitively diagnosed with T2DM. After evaluating the patients with cardiovascular high-risk factors such as coronary heart disease, obesity, dyslipidemia, etc., the previous hypoglycemic regimen of insulin aspart 30 injection (32 U subcutaneous injection in the morning and evening), combined with acarbose capsules (100 mg, 3 times/d) and metformin hydrochloride (0.5 g, 2 times/d) was adjusted on the basis of retaining metformin treatment, and combined with semaglutide injection (0.5 mg, 1 time/week subcutaneous injection) to control blood glucose. After simplifying the hypoglycemic method, blood glucose control was good, and the patient was satisfied. Glucagon-like peptide-1 receptor agonist semaglutide is glucose-dependent and hypoglycemic, which can effectively reduce blood sugar, with low risk of hypoglycemia and high safety. At the same time, it has a good effect on cardiovascular benefit and weight loss.

The clinical data of a patient with type 2 diabetes mellitus and overweight admitted to the Sixth Affiliated Hospital of Guangzhou Medical University treated with semaglutide were retrospectively summarized, and related literatures were reviewed. This patient was a middle-aged man with poor blood glucose control with oral drugs in the past and overweight. On the basis of oral metformin, acarbose combined with insulin glargine treatment, the fasting blood glucose and body weight decreased by 5 kg after subcutaneous injection of liraglutide once a day was adjusted to subcutaneous injection of semaglutide once a week. Clinically, the use of semaglutide in patients with type 2 diabetes and overweight can effectively control blood sugar and reduce weight. Patients with type 2 diabetes can be treated with semaglutide in combination with their clinical characteristics.

A patient with type 2 diabetes mellitus who was newly diagnosed in the Department of Endocrinology of Hainan Cancer Hospital was retrospectively analyzed after being switched to sequential therapy with glucagon-like peptide-1 receptor agonist (GLP-1RA) after intensive insulin treatment. The 47-year-old male patient was admitted to the hospital due to "dry mouth and poly-drinking for 6 years". After admission, all relevant examinations were completed, and the diagnosis of type 2 diabetes, moderate fatty liver, hyperlipidemia, and hypertension grade 1 (high risk) was confirmed. Intensive insulin therapy was given, combined with oral drug therapy to control blood sugar (insulin was gradually reduced, and the total course of treatment was 19 days, and then GLP-1RA treatment was switched to control blood sugar. Finally, the simplified regimen was semaglutide injection 0.5 mg, subcutaneous injection once a week. The patient's blood sugar control was satisfactory, blood lipids, weight and blood pressure were improved to varying degrees compared with before, and liver fat was significantly reduced.

A newly diagnosed obese patient with type 2 diabetes mellitus admitted to the Department of Endocrinology of Taiyuan Central Hospital was retrospectively analyzed after intensive insulin therapy, converted to sequential treatment with semaglutide injection, and finally stopped taking hypoglycemic drugs to achieve clinical remission. The patient was a middle-aged man with abdominal obesity, mainly due to "polyuria, dry mouth, and polydipsia for more than 40 days, aggravated for 2 days". After admission, relevant laboratory tests were completed, and the diagnosis of type 2 diabetes was confirmed. The blood glucose level was significantly increased at the beginning of the disease. Considering the glycotoxicity period, subcutaneous insulin pump was given to intensify hypoglycemic treatment in the early stage, and the insulin dose was gradually reduced. The sequential adjustment was made to semaglutide injection 0.5 mg (increased from 0.25 mg to 0.5 mg), once per week, combined with long-acting insulin once a night in the early stage, and then treated with single semaglutide injection. After the blood glucose control was stable, the drug dose was gradually reduced until discontinued. After discontinuation of hypoglycemic drugs for 3 months, the patient's blood glucose remained within the target range, suggesting that type 2 diabetes was remitted. Semaglutide has a remarkable weight loss effect, and at the same time has the effect of improving the function of pancreatic islet β cells.

This article reports the diagnosis and treatment process of a type 2 diabetic patient who was treated in the Department of Endocrinology of the Second Hospital of Traditional Chinese Medicine in Guangdong Province after intensive insulin therapy and switched to semaglutide therapy and reviews the literature. The patient was a 34-year-old male who was admitted to the hospital due to "repeated dry mouth, poly-drinking for more than 5 years, aggravated for 1 month". After admission, various examinations were completed and type 2 diabetes was clearly diagnosed. After discharge, the patient was treated with insulin pump combined with oral hypoglycemic drugs. After discharge, the patient was changed to semaglutide (0.5 mg, once a week) combined with insulin glargine (subcutaneous injection 18 U before breakfast) and dapagliflozin (10 mg, once a day). The blood sugar was well controlled. After that, the patient gradually reduced the dose of insulin and oral drugs. Now, semaglutide alone is used to reduce blood sugar, and the blood sugar control can be achieved. Semaglutide is a glucagon-like peptide-1 receptor agonist that can be used in combination with insulin and other oral hypoglycemic drugs to smoothly reduce glucose, and can be used for maintenance therapy after intensive therapy.

This article reports the diagnosis and treatment of a newly diagnosed obese type 2 diabetic patient. The patient presented with dry mouth, polydipsia, polyuria, obesity, dyslipidemia, abnormal liver function and fatty liver. After admission, all tests were improved to confirm the diagnosis of type 2 diabetes. The patient was 185 cm in height, 98.5 kg in weight and 28.79 kg/m in body mass index²Obese, treated with semaglutide combined with dapagliflozin tablets. Follow-up six months later, it was found that the patient had good blood sugar control, no hypoglycemia symptoms, weight loss, normal liver function indexes, and fatty liver disappeared. Therefore, for newly diagnosed type 2 diabetes patients with obesity, if there is a contraindication of metformin, glucagon-like peptide-1 receptor agonist can be considered as the first choice for treatment.