Editor's note:

In the Third People's Hospital of Luoyang, the treatment and research of endocrine and metabolic diseases are in full swing. As an expert in this field, Professor Tian Junhang has extensive experience in clinical research on metabolic disease drugs. Recently, the Clinical Research Promotion Foundation had the honor to interview Professor Tian. He has his own understanding of the principle of "truth, goodness and beauty" in clinical trials, and believes that the country should start from the top-level design to improve the medical system.

Written by Mao Donglei

Current status and challenges of metabolic diseases in Luoyang

Professor Tian Junhang first introduced the current situation of metabolic diseases in Luoyang. As a medium-level representative of China's overall development, Luoyang is currently dominated by diabetes and obesity in endocrine and metabolic diseases. This is a chronic epidemic and one that is constantly evolving.
 

Professor Tian Junhang, Director of the Department of Endocrinology, Luoyang Third People's Hospital.

He has successively served as a member of the Henan Endocrine Society, a member of the Standing Committee of the Endocrinology Group of the Henan Hypertension Research Association, a member of the Henan Endocrinology Society of Integrated Traditional Chinese and Western Medicine, a vice chairman of the Luoyang Endocrine Society, and a member of the Luoyang Medical Technology and Medical Accident Identification Group.

The incidence of diabetes continues to be at a peak, and obesity is an important prerequisite for it. In recent years, the incidence of obesity in adults is as high as 30%~50%, obesity is now regarded as a disease, it induces diabetes, cardiovascular and cerebrovascular diseases, osteoporosis, and even affects fertility, resulting in premature ovarian failure, decreased libido, abnormal menstruation, sperm quality decline and other disorders, and even obese patients are difficult to find a partner, which has become a psychological and social burden.

Obesity is not only a challenge for individuals, but also for society and the country. At present, there are limited effective methods for the treatment of obesity, and the corresponding drugs have not been included in the scope of medical insurance. This is a source of deep concern for the families of obese patients, and it is also a headache for society.

Medical care and society work together

Professor Tian Junhang believes that it is the most important means to prevent the occurrence of obesity and thus prevent diabetes. It is not enough to speak from the medical level alone, but requires the joint efforts of the state and society, including the comprehensive role of medical care, education and other factors. Improving environmental factors or slowing the development of these chronic epidemics. Apart from pharmaceutical and medical interventions, there are relatively few interventions at the social level. Professor Tian believes that it is important to educate patients to improve their lifestyle and bad habits, and it is often futile to rely only on drug intervention and ignore psychological counseling and lifestyle adjustment.

When it comes to hypoglycemic and weight-loss drugs, metformin has been regarded as a "miracle drug" for more than a decade. It has a mild appetite improvement and weight loss effect. In addition, metformin can also improve insulin resistance and reduce the symptoms of polycystic ovary syndrome. Metformin is used as a first-line drug in major global guidelines.

However, metformin has not been shown to definitively prevent the development of diabetes. The pathogenesis of diabetes mellitus is complex, and considering the rapid development of current biomedical technology, especially the progress of molecular biology, insulin has evolved from human insulin to insulin analogues. These technologies also include the biosynthesis of anti-lipid metabolism drugs such as GLP-1, GIP, and GCG, and GLP-1 single and dual receptor drugs including insulin have been synthesized in large quantities.

Since the advent of insulin hypoglycemic technology, the main adverse reaction is hypoglycemia, which is an unavoidable problem for all insulin varieties. It would be of great significance to develop a technology that can lower blood sugar without producing resistance. At present, emerging technologies such as small molecule peptides, such as GIP, are receiving widespread attention.

These techniques have been shown to improve glucose and lipid metabolism and weight loss. They can promote insulin secretion and lower blood sugar during high blood sugar; When the blood sugar is normal or low, it does not participate in the release of insulin, and at the same time can improve other metabolic abnormalities, such as acting on the gastrointestinal tract, increasing satiety, promoting lipid metabolism, reducing appetite, and thus playing a role in weight loss. This mechanism of action is equally effective for normal people without affecting blood glucose concentrations. Semaglutide, as a representative drug of this type of technology, is still in short supply despite its high price.

Among the hypoglycemic drugs, Professor Tian specifically mentioned the DPP-4 target, and sitagliptin, which was first developed by Merck, belongs to this class of drugs. DPP-4 inhibitors regulate insulin secretion by improving the body's natural GLP-1 concentrations. The natural concentration of GLP-1 in the human body is very low and the half-life is very short, no more than 10 minutes. DPP-4 inhibitors allow naturally produced GLP-1 in the body to act longer by inhibiting the enzyme that breaks down GLP-1. These drugs promote insulin secretion and lower blood sugar when blood sugar is high; When blood sugar is low, it reduces insulin secretion or promotes glucagon secretion to keep blood sugar stable.

In China, a new generation of DPP-4 inhibitors, represented by CGeneTech's senagliptin, has been approved for marketing by improving Merck's sitagliptin and carrying out rigorous and high-quality clinical trials. The Third People's Hospital of Luoyang City, as one of the national multi-center participating units, also participated in the phase III clinical trial of the drug.

Professor Tian commented that the hypoglycemic effect of sengliptin is relatively stable and mild, and it is a neutral hypoglycemic drug, and its biggest feature is that it will not cause hypoglycemia, which is especially suitable for the elderly and people with high-risk factors for cardiovascular and cerebrovascular diseases.

During the clinical trial, the investigators established a good friendship with the patients and their families, providing them with various conveniences. At the end of the trial, some subjects presented flowers and pennants to the CRC as a token of their gratitude. CRCs play an important role in clinical trials, and they are grateful for the close bond they have developed with patients and their families, and they are grateful to them for being like friends.

The "Truth, Goodness and Beauty" of Clinical Trials

Professor Tian believes that clinical trials not only provide many medical conveniences for subjects, but also ensure that their rights and interests are fully protected. The Third People's Hospital of Luoyang City has always put the requirements of GCP, that is, the rights and interests of subjects, in the first place.

He further elaborated on the principle of "truth, goodness and beauty" in clinical trials. True, i.e., the authenticity of clinical trials. The investigator should ensure the authenticity and quality of all data, strictly follow the inclusion standards and GCP requirements, and all data can be traced from the enrollment of subjects to the end of the trial. The institute has been verified by the national bureau many times, and all the verification data are true and reliable, ensuring the authenticity of the test.

Goodness, that is, treating subjects well. They always put the principle of protecting subjects first, strictly following GCP requirements, and making friends with patients and subjects, which is essential to improve subject compliance and prevent dropout.

Beauty, that is, the beauty of the doctor's mind. The researcher adheres to the concept of "sometimes to heal, often to help, always to comfort", and regards the patient as his own family. Guided by this famous quote from American physician Justin Trudeau, researchers are committed to executing clinical trials flawlessly, providing the best care and service to their subjects.

Recommendations and prospects for drug development

Finally, Professor Tian gave several suggestions on how to improve the safety and effectiveness of drugs, and even eliminate some complications, from the perspective of drug development.

First of all, in the early stage of drug development, in-depth research and selection of potential targets should be carried out, which is the key to improving drug efficacy. At the same time, the selection of trial endpoints is also crucial to ensure that the therapeutic effect of the drug is accurately reflected.

Second, they expect AI to play a greater role in target selection and drug discovery in the future of new drug development. With the assistance of AI technology, potential drugs can be screened and discovered more efficiently, accelerating the process of new drug development.

Thirdly, precision medicine is an important way to achieve highly individualized treatment. For example, the idea of a smart insulin capsule, which can be implanted with a chip to precisely control the release of insulin, is expected to solve the treatment problem of patients with type 1 diabetes. In addition, precision medicine also involves the precise diagnosis of genes, and in the future, gene therapy may be used to improve the expression of genes, so as to treat diseases caused by abnormal gene expression.

In the process of drug development, attention should be paid to the two-way regulatory effect of drugs to avoid serious adverse reactions, such as hypoglycemia. By precisely modulating the mechanism of action of drugs, safer and more effective therapeutic effects can be achieved.

Professor Tian said that drug development is a complex and lengthy process, which requires comprehensive consideration of target selection, clinical endpoints of trials, intelligent technology, precision medicine and other aspects. He believes that more innovative, safe and effective drugs will be available in the future.
 

A message to young doctors and the improvement of the medical environment

As a clinical doctor for many years, Professor Tian has a deep understanding of how young doctors can continue to advance and develop in this industry. He believes that young people should continue to accumulate experience through clinical practice when learning modern medical concepts, knowledge and techniques. Patients should be treated as relatives, and medical treatment must not be regarded as a means of personal gain. If money is put first and the interests of patients are neglected, the reputation will be damaged, and the gains will outweigh the losses, and it will be difficult to improve medical skills.

As a retired clinician, Professor Tian is deeply happy, but at the same time, he believes that the development of medical care and the growth of individuals need a better environment and the support of national policies.

Nowadays, doctors are under pressure with various indicators that have to spend a lot of time and effort in order to complete them. Therefore, he hopes that the country can improve the medical environment at the macro level, so that doctors can concentrate on treating diseases and saving lives, instead of being distracted by other trivial matters. At the same time, he believes that doctors' income should be decoupled from their workload to avoid overtreatment and save money on medical insurance. Doctors can be given a reasonable subsidy, but the income should not be directly linked to the number of surgeries or outpatient visits.

As a veteran doctor, Professor Tian sincerely hopes that the state can improve the medical environment and system, and provide scientific research funds and due subsidies for medical staff to reduce their burden. "It is necessary for the state to start from the top-level design and formulate a sound system to provide a strong guarantee for the healthy development of the medical industry." He concluded. (Article source: Clinical Research Promotion Public Welfare Fund)