How to choose a hypoglycemic plan for patients with type 2 diabetes with multiple complications/comorbidities such as ASCVD?

*For medical professionals to read for reference only.
In the face of patients with a variety of underlying diseases and complications, and comprehensive management of multiple factors, it is very important to choose a hypoglycemic plan that can bring more benefits in addition to hypoglycemia
.

Case patient, female, 75 years old
.

Chief complaint: dry mouth for 22 years, chest tightness, palpitations for 2 months, aggravation and fatigue for 2 days
.

History of present illness: The patient reported that 22 years ago, there was no obvious incentive for dry mouth and polydipsia.
He went to a local hospital for treatment.
The fasting blood sugar was measured to be 13.
6mmol/L, and he was diagnosed with type 2 diabetes.
"Pill" hypoglycemic therapy for more than 4 years
.

Afterwards, he went to a private clinic to take traditional Chinese medicine for 2 years; 16 years ago, due to poor blood sugar control, he was hospitalized in a local hospital.
He was treated with "Insulin Aspart 30" 8U before breakfast and dinner, and 50mg of "Acarbose Tablets" was taken orally.
3 times a day for hypoglycemic therapy; 12 years ago, due to poor blood sugar control, he was hospitalized in a local hospital.
The adjustment plan was "insulin glargine" 20U, "insulin aspart" 8U-8U-8U, "metformin hydrochloride tablet" 0.
5 g Lowering blood sugar 3 times a day so far, the normal blood sugar control is not good; 2 months ago, chest tightness and palpitations occurred repeatedly, especially at night, and gradually relieved after taking "nitroglycerin" orally; during the course of the disease, numbness of the limbs occurred intermittently, accompanied by a lot of Foamy urine, no obvious blurred vision; there was no obvious cause for the aggravation of the above symptoms 2 days ago, and it was accompanied by symptoms of general malaise.
In order to seek further diagnosis and treatment, I came to our hospital.
Department, since the onset of the disease, the patient has been conscious and in good spirits, the diet has not been strictly controlled, the stools are dry, once every 2 days on average, the urine is normal, and the recent weight loss is about 2kg
.

Past history: 5-year history of "hypertension" and 8-year history of "coronary heart disease"
.

Personal history: No significant abnormality
.

Family history: history of type 2 diabetes and pancreatic cancer in younger brother
.

Physical Exam Notes: Body Mass Index (BMI)
.

Body temperature 36.
3 ℃, respiration 19 beats/min, heart rate 89 beats/min, blood pressure 157/67 mmHg
.

Auxiliary examination-laboratory examination-Note: glycosylated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-c), low density lipoprotein cholesterol (LDL-c)
.

-Physical examination-diagnosis 1.
Type 2 diabetic peripheral neuropathy, diabetic retinopathy, stage I diabetic nephropathy, 2.
Coronary atherosclerotic heart disease, sinus rhythm, poor cardiac function, class II (NYHA classification) 3.
Hypertension 3.
Grade (very high risk group) 4.
Bilateral common carotid artery plaque 5.
Bilateral lower extremity arteriosclerosis and plaque 6.
Hyperuricemia 7.
Fatty liver 8.
Binocular senile cataract treatment plan I Phase I: Before admission "Insulin glargine" 20U subcutaneous injection before bedtime, "Insulin aspart" 8U subcutaneous injection before three meals, "Metformin hydrochloride tablets" 0.
5g three times a day, poor blood sugar control, fasting blood sugar 11.
96mmol/L, 2 after meals Hourly blood sugar 24.
23mmol/L, HbA1c10.
3%
.

I Phase II: Insulin aspart 30 16U before breakfast, 14U before dinner, liraglutide injection [0.
6mg (initial), subcutaneous injection once a day (QD)], dapagliflozin tablets during hospitalization 10mg QD orally
.

Then the dose was adjusted according to the patient's blood sugar condition, and the dose of insulin aspart was gradually reduced by 30 units to 10U before breakfast and 8U before dinner, and the dose of liraglutide injection was adjusted to 1.
2mg QD
.

I blood glucose profile I The regimen at discharge was adjusted to: insulin aspart 30 early 8U - late 8U + liraglutide 1.
2 mg + dapagliflozin 10 mg
.

I Phase III: After 3 months of treatment, the regimen of liraglutide 1.
2 mg + dapagliflozin 10 mg (in the case of ideal blood sugar control in patients, the dose of insulin aspart 30 is gradually reduced until insulin is discontinued)
.

I follow-up and treatment for 3 months, the patient's blood sugar has improved significantly.
The blood sugar curve of the patient before and after treatment is as follows: Changes of other data before and after treatment: ★ Doctor interviews with the medical community: When you meet such patients in clinic, how do you choose medication? In this case, how did you consider the final hypoglycemic plan? Dr.
Chen Guojuan: In clinical practice, we often encounter such patients with type 2 diabetes mellitus (T2DM) with multiple comorbidities/complications including atherosclerotic cardiovascular disease (ASCVD).
Calorie calculation and life>
.

"CDS Guidelines 2020" [1] suggests that metformin should be used as a first-line hypoglycemic drug unless contraindications or intolerances are excluded, but due to ischemia and hypoxia in the patient (mild skin ulceration of the foot) , and complicated with diabetic nephropathy, so metformin was not selected
.

In terms of insulin selection, considering that the patient's pre-hospital treatment plan (4 times a day subcutaneous insulin injection) was complicated, and the blood sugar before and after meals were poorly controlled, the patient was found to have severe insulin resistance after completing relevant examinations
.

Therefore, the patient's insulin injection regimen was adjusted, and the starting insulin was calculated according to 0.
5U/kg/d, which was adjusted to premixed insulin aspart 30 16U before breakfast and 14U before dinner to lower blood sugar
.

In addition, considering that the patient also has cardiovascular disease, and the body weight and waist circumference are severely exceeded, according to the "CDS Guidelines 2020" [1]: patients with ASCVD or high risk factors for ASCVD, heart failure or chronic kidney disease (CKD) type 2 For diabetic patients, on the basis of life>
.

In conclusion, according to the characteristics of this patient, liraglutide combined with dapagliflozin and insulin were used to lower blood sugar
.

Liraglutide has been shown to have a significant cardiovascular protective effect in previous cardiovascular outcome trials, and can improve metabolic factors such as hypertension, obesity, and dyslipidemia
.

After treatment, the patient's blood sugar gradually stabilized and reached the ideal blood sugar.
After 3 months of follow-up, the patient's HbA1c, body weight, waist circumference, and blood lipids were significantly improved compared with those before admission.
The patient himself is also very satisfied with the results, but for the improvement of ASCVD, Longer follow-up observations are required
.

Medical community: Based on this case, can you talk about the additional benefits that liraglutide brings to patients in addition to lowering blood sugar? Dr.
Chen Guojuan: Combined with clinical experience and related research [2-9], liraglutide can effectively help patients lose weight, reduce waist circumference, and improve metabolic indicators such as hypertension and dyslipidemia
.

In this case, after the patient applied liraglutide, cardiovascular risk factors such as body weight, waist circumference, and blood lipids were significantly improved, suggesting that liraglutide did bring benefits other than hypoglycemic to the patient
.

At the same time, in the Cardiovascular Outcomes Trial (LEADER study) [10], liraglutide can significantly reduce the risk of major adverse cardiovascular events (MACE) in T2DM patients with cardiovascular disease or high-risk factors for cardiovascular disease, At the same time, it reduces the risk of cardiovascular death and all-cause mortality, and brings cardiovascular benefits to patients
.

Therefore, in the clinical encounter of such diabetic patients with ASCVD or cardiovascular risk factors, the comprehensive metabolic indicators and the patient's economic status can be combined to comprehensively evaluate the patient's hypoglycemic program, so as to ensure that the patient can obtain the target on the basis of the indicators.
Multiple metabolic and cardiovascular benefits improve long-term patient outcomes
.

★ Director commented on the medical community: The patient in this case has abdominal obesity.
After treatment, his blood sugar and waist circumference have been significantly reduced
.

Could you please talk about the improvement of waist circumference, what is the significance of blood sugar control in T2DM patients? Director Ma Mingfu: Abdominal obesity (waist circumference ≥ 90 cm in men and ≥ 85 cm in women) is an external manifestation of visceral fat accumulation, and is also one of the high-risk factors for diabetes and one of the diagnostic criteria for metabolic syndrome [1].
Among Chinese T2DM patients, Abdominal obesity accounts for about half of them.
Under the continuously updated and iterative hypoglycemic concept, more attention should be paid to the treatment of abdominal obesity for the treatment of overweight or obese T2DM [11]
.

Excessive lipids are mainly manifested as abdominal obesity on the outside, but may lead to fat deposition in tissues and organs such as the pancreas and liver, resulting in a decrease in the function of the pancreas to secrete insulin and aggravate insulin resistance at the same time; Deposition in muscle tissue, etc.
, or accumulation of lipids in the pancreas, can also lead to impaired insulin secretion, negatively affecting the progression of diabetes [12]
.

Studies have shown that liraglutide in the treatment of abdominal obesity in T2DM patients is beneficial to reduce the area of ​​visceral fat, improve the patient's insulin secretion function, and improve insulin resistance [13,14]
.

For this case, the patient's waist circumference was 102cm before admission, which is typical of abdominal obesity.
After treatment with liraglutide, the waist circumference was reduced to 96cm, indicating that liraglutide is beneficial to reduce the patient's visceral fat to a certain extent
.

Medical community: Which patients is liraglutide suitable for? From your experience with liraglutide over the years, what would you say about the drug? Director Ma Mingfu: Liraglutide is a type of GLP-1RA, which mainly binds to the GLP-1 receptor on pancreatic beta cells, thereby promoting insulin secretion
.

In addition, it can also inhibit glucagon secretion, delay gastric emptying, suppress appetite, etc.
, through these methods to achieve hypoglycemic, weight loss and other effects
.

At the same time, liraglutide has multiple cardiovascular and renal benefits
.

The Guidelines for Primary Prevention of Cardiovascular Disease in China [15] clearly pointed out that adult T2DM patients with ASCVD risk factors, on the basis of life>
.

Moreover, the "CDS Guidelines 2020" also recommends that in T2DM patients with ASCVD or high cardiovascular risk factors, regardless of whether their HbA1c is up to standard, as long as there are no contraindications, GLP-1RA or GLP-1RA with evidence of ASCVD benefit should be added to metformin.
SGLT2i; in addition, related studies have shown that for T2DM patients without the above diseases, GLP-1RA can reduce the risk of hypoglycemia and avoid weight gain caused by insulin therapy while effectively reducing blood sugar.
It is also a clinical treatment for T2DM.
Preferred [1]
.

It can be said that liraglutide is an "all-star" hypoglycemic drug that integrates hypoglycemic, weight loss, cardiovascular benefits, and renal benefits
.

It is hoped that in the future, with the further implementation of the guidelines and the accumulation of clinical experience, more diabetic patients can achieve multiple benefits such as hypoglycemic, weight loss, and cardio-renal protection through such drugs
.

References: [1] Diabetes Branch of Chinese Medical Association.
International Journal of Endocrinology and Metabolism.
2021; 41(05): 482-548.
[2] Marre, et al.
Diabet Med.
2009; 26; 268–278 (LEAD- 1).
[3] Nauck, et al.
Diabetes Care.
2009; 32; 84–90 (LEAD-2).
[4] Garber, et al.
Lancet.
2009; 373: 473–481 (LEAD-3).
[5] Zinman, et al.
Diabetes Care.
2009; 32: 1224–1230 (LEAD-4).
[6] Russell-Jones, et al.
Diabetologia.
2009; 52: 2046– 2055 (LEAD-5).
[ 7] Buse, et al.
Lancet.
2009; 374: 39–47(LEAD-6).
[8] Pratley, et al.
Lancet.
2010: 375; 1447– 1456.
[9] Zinman, et al.
Diabetes, obesity and metabolism.
2012;14:77-82.
[10]Marso SP,et al.
N Engl J Med.
2016;375(4):311322.
[11]Expert consensus on comprehensive management of type 2 diabetes mellitus with obesity in China[J] ].
Chinese Journal of Diabetes.
2016; 8(11): 662-666.
[12] André Tchernof, et al.
Physiol Rev.
2013; 93: 359–404.
[13] Han Jie, et al.
Sichuan Medicine.
2020; 41 (8): 854-858.
[14] Sun Qian, et al.
Sichuan Medicine.
2020; 41(6): 614-618.
[15] Cardiovascular Branch of Chinese Medical Association.
Chinese Journal of Cardiovascular Diseases.
2020; 48(12):1000-1038.
-End-"This article is only used to provide scientific information to medical and health professionals, and does not represent the platform's position" Contribution / reprint / business cooperation, please contact: pengsanmei@yxj.
org.
cn