In 2021, the "Opening Lecture" is divided into three major themes, which lasted five sessions, of which the theme conference of "The 'New' Road Course of Diabetes Management" has just come to an end, and several experts have brought wonderful academic speeches to everyone.
The "new" journey of diabetes management
(Phase 1)
Professor Chen Lulu and Professor Xu Chun were invited to serve as the chairmen of the conference, and Professor Jiang Sheng, Professor Pan Qi, Professor Li Guangwei and Professor Xiao Xinhua were invited as guest speakers.
Gehua stopped, promoting the process of China's exploration of metformin
Professor Jiang Sheng The First Affiliated Hospital of Xinjiang Medical University
Professor Jiang Sheng first briefly elaborated on the evidence-based accumulation of metformin over the past 60 years, and then gave detailed answers to some questions of concern to clinicians (Figure 1):
Figure 1 Common problems encountered by clinicians in the use of metformin
(1) Chinese patients with type 2 diabetes mellitus (t2dm) use metformin, and the hypoglycemic effect is not affected by weight. (2) Patients with t2dm using insulin can get more benefits with metformin therapy without increasing the risk of hypoglycemia. (3) If patients with t2dm have gastrointestinal intolerance after using metformin, they can be improved by the following methods: (1) start with a small dose and gradually reach the optimal dose; (2) replace the ordinary metformin tablets with extended-release tablets (Gehuazhi ®XR), which ®can significantly reduce gastrointestinal adverse events and improve gastrointestinal tolerance. (4) Metformin has a clear cardiovascular benefit, and previous studies have confirmed that patients treated with metformin have significantly reduced all-cause mortality and risk of heart failure.
Diabetes and tumors are right and wrong
Pan Qi is a professor at Beijing Hospital
Professor Pan Qi believes that diseases such as insulin resistance, obesity, and t2dm are related to tumor risk; hyperinsulinemia, glycolipid abnormalities, inflammatory factors, and adipokines may promote tumor cell proliferation. The effect of various hypoglycemic drugs on the risk of tumorigenesis is different, but it is clear that metformin can reduce the overall cancer incidence and mortality, and its anti-tumor mechanism has two main aspects, on the one hand, by activating ampk, the mtor signal decline directly inhibits tumor cell proliferation; on the other hand, by reducing insulin levels and reducing insulin receptor activity, it further affects the pi3k/akt signaling pathway, thereby inhibiting cell proliferation (Figure 2).
Fig. 2 Antitumor mechanism of metformin
Metformin and prevention of diabetes and cardiovascular disease
Professor Li Guangwei is a professor at Fuwai Hospital, Chinese Academy of Medical Sciences
Professor Li Guangwei first emphasized the importance of diabetes management attaching importance to long-term outcomes, and then pointed out that metformin can greatly reduce the risk of all-cause death, cardiovascular death and heart failure in patients with diabetes (Figure 3), and if there is no contraindication or intolerance, early initiation of metformin in t2dm is beneficial to reduce the long-term cardiovascular risk and death risk of patients. It is well known that insulin resistance not only induces t2dm, but is also associated with cardiovascular and cerebrovascular diseases, and metformin improves insulin sensitivity, which fundamentally improves the cardiovascular outcome of patients with t2dm.
Figure 3 Metformin reduces the risk of all-cause death, cardiovascular death, and heart failure in patients with diabetes
The focus and difficulty of hypoglycemia diagnosis and treatment
Xiao Xinhua is a professor at Peking Union Medical College Hospital
Professor Xiao Xinhua pointed out that in the clinic, how to identify the type of hypoglycemia is the focus and difficulty of treating hypoglycemia: patients with postprandial hypoglycemia cannot exclude insulinoma, and imaging examination is required for suspicious patients in time; congenital hyperinsulinic hypoglycemia (chi) does not have tumor problems, and most patients respond to diazazine treatment; insulin autoimmune syndrome (IAS) is manifested in high insulin levels and low c-peptide levels in hypoglycemia Non-islet cell neoplasmic hypoglycemia (NICTH) is characterized by low insulin levels but elevated IGF-2, often associated with tumors.
Q&A and discussion
q1. The incidence of diabetes has soared, and there are new therapeutic drugs on the market in the clinic, is metformin still the main force in reducing diabetes?
Professor Li Guangwei believes that the new hypoglycemic drugs have indeed shown their excellent efficacy, but the control of the basic causes and pathogenesis of diabetes has yet to be confirmed. At present, the status of metformin is still irreplaceable.
Professor Pan Qi further added that in the RCT study of the new drug, about 60% of the subjects used metformin at the same time; in addition, the new hypoglycemic drug has a short clinical application time, and the experience of using metformin has exceeded 60 years, clinicians will be more confident of playing its efficacy to the best, and many studies have found that metformin has benefited multiple organs.
q2.From the current stage, the enlightenment or guiding significance of China's diabetes prevention research (CDPP) to the clinic?
Professor Jiang Sheng said that for the prevention of diabetes, in addition to lifestyle interventions, there is no exact evidence-based drug, which can guide clinicians to apply it to t2dm prevention with confidence and boldness. Future CDPP findings may provide strong evidence that metformin can be applied to diabetes prevention.
q3.For grassroots doctors, how to prevent hypoglycemia in the treatment of diabetic patients?
Professor Xiao Xinhua pointed out that grass-roots doctors should first pay attention to the collection of medical history; secondly, in terms of oral drugs, they should try to choose hypoglycemic drugs with less risk of hypoglycemia, such as metformin; in terms of insulin therapy, insulin regimens should be selected based on the specific conditions of patients.
Summary: Gehuazhi ® has been in the clinic as a classic drug for decades, and as Professor Jiang said, Chinese research has given Gehuazhi ® some Chinese experience, such as avoiding gastrointestinal reactions, drug dose adjustment, etc. It is hoped that in the future, clinicians can exert better efficacy with Gehuazhi ®.
In addition, type 2 diabetes is a high-risk tumor disease, and certain hypoglycemic drugs may increase the risk of tumorigenesis in diabetic patients, and the idea that metformin can reduce the risk of tumorigenesis has been confirmed. Professor Pan's speech provides an extremely favorable direction for optimizing diabetes treatment options in the future clinic.
In the earliest studies of ugpds, metformin was confirmed to have cardiovascular benefits. It is well known that insulin resistance not only induces t2dm, but also closely related to cardiovascular and cerebrovascular diseases, and metformin can improve insulin sensitivity, which is a fundamental improvement in cardiovascular outcomes in patients with t2dm.
Regarding the prevention and treatment of hypoglycemia, Professor Xiao Xinhua explained the key points and difficulties of hypoglycemia diagnosis and treatment in a simple and simple way, from which we learned the identification of various hypoglycemia types, including the way of locating islet cell tumors and the treatment of congenital hypoglycemia.
(Phase 2)
Professor Guo Lixin and Professor Kuang Hongyu were invited to the conference as the chairmen of the conference, and Professors Liao Lin, Xu Chun, Zhang Haohao and Xiao Xinhua made wonderful speeches.
In order to standardize the diagnosis and treatment of diabetes and cardiovascular diseases, this "Open Lecture" academic exchange activity adopts the form of online teaching, combined with wonderful academic interaction, systematic theoretical learning and practical discussion, to help doctors improve their scientific research skills, promote information exchange and talent training.
Look at the reasons for the first choice of metformin from another angle
Lin Liao is a professor at the First Affiliated Hospital of Shandong First Medical University
Professor Liao Lin mentioned that many authoritative guidelines recommend metformin as a first-line hypoglycemic drug for diabetic patients, and the reasons for this are mainly the following three reasons: (1) metformin monopharmaceutical drug can achieve strong hypoglycemic and no risk of hypoglycemia; (2) insulin resistance is the pathophysiological basis of t2dm and cardiovascular disease, and metformin can activate ampk, thereby improving insulin resistance (Figure 4) ;(3) Metformin is the earliest hypoglycemic drug to prove cardiovascular benefits. And there is a growing body of evidence that metformin has the effect of improving cardiovascular outcomes.
Fig. 4 Metformin improves the pathophysiology of insulin resistance
Metformin has multiple advantages beyond hypoglycemic reduction
Xu Chun is a professor at the Third Medical Center of the PLA General Hospital
Professor Xu Chun pointed out that in addition to hypoglycemicity, metformin has many benefits in other areas: (1) metformin has a protective cardiovascular effect on patients with t2dm and is recommended by guidelines as one of the hypoglycemic drugs with cardiovascular protective effects; (2) metformin can treat polycystic ovary syndrome and non-alcoholic fatty liver disease caused by insulin resistance; (3) metformin has an anti-aging effect, and can also reduce the risk of tumors by directly activating ampk and improving insulin resistance ;(4) Metformin is able to improve glucose tolerance by modulating the t2dm intestinal flora.
Metformin is explored for mechanisms that improve insulin sensitivity through hypothalamic mc4r
Zhang Haohao is a professor at the First Affiliated Hospital of Zhengzhou University
Professor Zhang Haohao pointed out that the mc4r gene can increase peripheral energy expenditure and insulin sensitivity, while metformin intervention can significantly upregulate hypothalamic mc4r expression (Figure 5), increase skeletal muscle ampk, sirt1 expression and mitochondrial quantity, thereby improving skeletal muscle insulin resistance.
Fig. 5 Metformin can upregulate hypothalamic mc4r expression
Chinese expert consensus on the optimization scheme of oral hypoglycemic drugs in adult patients with type 2 diabetes mellitus
Professor Xiao Xinhua proposed that diabetes involves multiple pathogenesis, and monotherapy is difficult to cover, so the benefits of early combination drugs are far greater than traditional ladder diagnosis and treatment. The triple regimen represented by metformin + dpp-4i + sglt2i is suitable for most t2dm patients, and at the same time, the triple regimen can achieve synergistic complementarity, optimize glycemic control, comprehensively improve metabolic indicators, have good safety, and the incidence of adverse reactions is not higher than that of single drug or binary regimen (Figure 6).
Figure 6 Recommended content of the triple optimization scheme of oral hypoglycemic drugs in patients with t2dm
q1. In patients with cardiovascular disease and diabetes mellitus, hypoglycemic directly enables sglt2i because it has antihypertensive and cardiovascular prognostic effects. There are also many examples of control successes. No line of metformin added. Do you have any suggestions for this? Is it recommended that metformin, which also has cardiovascular benefits, as recommended by guidelines, be followed by the patient's situation?
Professor Zhang Haohao believes that when doctors prescribe drugs, they should not only consider the factors of blood glucose and comorbidities, but also assess the risk of other diseases that affect the safety of patients' lives, and patients with cardiovascular disease and diabetes mellitus should use sglt2i.
q2. The optimal dose of metformin is 2000mg / day, but the more used in the clinic is 1000 and 1500mg / day, should the patient adhere to the increase or directly add other hypoglycemic drugs when the patient can tolerate it?
Professor Xu Chun believes that if the patient's oral metformin 1000 or 1500 mg / day blood glucose control is not ideal, it is recommended to increase the dose to 2000 mg / day; if the patient really can not tolerate the optimal dose of metformin, other hypoglycemic drugs can be added to the original 1000 or 1500 mg / day.
q3. If t2dm patients treated clinically with the consensus triple regimen have a more pronounced weight loss, higher sensitivity to drugs, or low blood glucose, and the patient is willing to want to return the drug, is there a regression plan?
Professor Xiao Xinhua pointed out that drug regression needs to be analyzed according to the specific situation of the patient, and the drug discontinued should be selected according to the patient's most obvious symptoms (weight loss, gastrointestinal reaction, etc.).
Concluding statement
Through the experts' detailed explanation of metformin from various angles, we have a deeper understanding of metformin. At present, there are many types of drugs on the market, how to apply in the clinic can play the maximum efficacy of the drug, so that patients have greater benefit has become a common topic of discussion, I hope that this activity can provide more help for everyone in the clinical work of the use of metformin.
With the progress of science, people's exploration of diabetes has never stopped, the authoritative guidelines continue to update, promoting the continuous improvement of diabetes treatment, metformin is still the authoritative guidelines unanimously recommended a line of hypoglycemic drugs, it is expected that in the future exploration, metformin will also bring us new surprises.
In the next second meeting, the big coffee will bring you the "Internet Era of Chronic Disease Management", so stay tuned!