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Treatment is "subtraction", efficacy is "addition", and innovative treatment strategies for T2DM patients are seen through real cases

 Last Update: 2023-01-06
 Source: Internet
 Author: User

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With a 20-year course of disease and an HbA_1c of 9.
7%, how to achieve high-quality management that balances effective hypoglycemia, hypoglycemia risk, and weight gain? Look down!

Human understanding of diabetes has a long history, and the pathogenesis of diabetes, mainly based on impaired cell function and β insulin resistance of pancreatic islets, is gradually clarified
.
With the continuous change of drug treatment strategies, more powerful and durable blood glucose control, less hypoglycemic response and weight gain have become clinical demands
.
In March this year, Degludec insulin liraglutide injection (IDegLira) launched in China has become an example
of "addition" and treatment "subtraction" because of its therapeutic advantages of synergistic complementarity between insulin and glucagon-like peptide-1 receptor agonist GLP-1RA.
The case in this article is very honored to invite Professor Li Sheli from the Department of Endocrinology and Metabolism of the Affiliated Hospital of Yan'an University, and we hope to understand the clinical treatment of IDegLira through the treatment
of innovative drugs.

Case data

The patient is a 67-year-old male who complains of high blood sugar for more than 20 years
.

History of present illness

The patient discovered high blood sugar more than 20 years ago, diagnosed with "T2DM (type 2 diabetes)", lifestyle treatment
.
Oral hypoglycemic drugs (OAD) began 14 years ago, combined with insulin glargine 10 years ago, and fasting blood glucose (FPG) 10.
09mmol/L was found in physical examination 2 months ago, blood glucose (2h PPG) 18mmol/L 2 hours after meals, glycated hemoglobin (HbA_1c) 9.
7%, regular diet and exercise, no numbness in the limbs, blurred disregard, no swelling
of the lower limbs.

Anamnesis

History of hypertension for 8 years, currently oral irbesartan tablets 75 mg once daily (QD); Dyslipidemia, currently oral atorvastatin 20mg QD lipid-lowering therapy
.

Family history

Deny a family history of diabetes and deny a history
of other specific diseases.

Patient medication

Basal insulin: Insulin glargine 22U QD
Oral hypoglycemic drugs: empagliflozin 10 mg QD; Metformin tablets 1.
0g twice daily (BID); Sitagliptin 100 mg QD
Other drugs: irbesartan tablets 75 mg QD; Atorvastatin 20 mg QD

General

Body temperature 36.
4°C, breathing 18 breaths/min, heart rate 73 beats/min
.

physical examination

Height 170cm, weight 75kg, body mass index (BMI) 26 kg/m^2, blood pressure (lying position) 135/70 mmHg
.

Laboratory tests

Blood glucose: HbA_1c9.
7%; FPG 10.
09mmol/L； 2h PPG 18.
9mmol/L；
Blood lipids: total cholesterol (TC) 3.
49mmol/L; Low-density lipoprotein cholesterol (LDL-c) 2.
5mmol/L; High-density lipoprotein cholesterol (HDL-c) 1.
62mmol/L; Triglycerides (TG) 0.
56mmol/L;
Liver function: alanine aminotransferase (ALT) 32U/L; Aspartate aminotransferase (AST) 29U/L;
Renal function: blood urea nitrogen 6.
29mmol/L, blood creatinine 54μmol/L;
Urinalysis: urine glucose+, proteinuria-, ketone bodies-, normal microscopy, albumin/creatinine ratio: 10.
7 mg/g
.

Other ancillary tests

ECG: sinus rhythm;
Carotid ultrasound: plaque formation at the beginning of the right subclavian artery, bilateral carotid plaque formation;
Fundus examination: no obvious bleeding and exudation in the fundus;
Abdominal ultrasound and other tests: no abnormalities
.

Table 1 Previous blood glucose monitoring and occurrence of hypoglycemia

Diagnosis of admission

1.
Type 2 diabetes peripheral vascular lesion 2, hypertension grade 2 3, dyslipidemia

Hypoglycemic regimens

IDegLira: 16 doses of QD;
Metformin: 1.
0g BID;
Empagliflozin: 10mg QD
.

After the treatment

During the treatment, the treatment regimen and dose were not adjusted, and the 2h PPG decreased from 18.
2mmol/L to 7.
2mmol/L, and the FPG decreased from 10.
02mmol/L to 5.
5mmol/L
.
No hypoglycemia occurred during treatment, and no weight gain
occurred.
There were gastrointestinal reactions at the beginning of treatment, and gastrointestinal reactions disappeared after that, and no other adverse reactions occurred
.

Table 2 Changes in blood glucose
during treatment of patients Table 3 Hypoglycemia, weight and adverse reactions during treatment of patients

Case summary

The elderly male with diabetes for 20 years successively used OAD sequential treatment, basal insulin + OAD combination therapy for nearly 10 years, monitoring HbA_1c9.
7%, FPG 10.
09mmol/L, 2h PPG 18.
9mmol/L; Patients who have previously had hypoglycemia, overweight, hypertension, and dyslipidemia require comprehensive management
while undergoing effective hypoglycemic therapy.
Considering the need and convenience of treatment, IDegLira 16 dose initiation therapy was applied to the patient, and the dipeptidyl peptidase IV.
-inhibitor (DPP-4i) was discontinued, and after one month of treatment, the patient's FPG was reduced to 5.
5mmol/L and 2h PPG to 7.
2mmol/L, and no hypoglycemia occurred during treatment.
Weight reduction of 3.
5kg, no other adverse reactions, reduction of one OAD, which is a more satisfactory result
for patients and doctors.

Doctor shares

Medical profession

In this case, the patient has a long course of disease and high blood sugar, and when choosing a treatment for such patients, the clinic usually chooses an intensive insulin regimen, what are your considerations for choosing IDegLira?

Director Li Sheli:
The Expert Consensus on Short-term Insulin Intensive Therapy for Type 2 Diabetes Mellitus ^[1] recommends that HbA_1c should be treated with the maximum tolerated dose of ≥ two OADs for more than 3 months Insulin augmentation regimens can be used ≥ 9.
0% of patients or patients who have been treated with basal insulin plus OAD for more than 3 months and have not met the HbA_1c target (≥ 7.
0%)
.
The patient meets the relevant conditions, but considering that the patient is an elderly patient, short-term intensive insulin therapy requires multiple daily (3~4 times) subcutaneous insulin injection, and also needs to cooperate with multiple daily blood glucose monitoring, which is not suitable for this patient
.

At the same time, the increased risk of weight and hypoglycemia that may be associated with exogenous insulin supplementation are all things we want to avoid when choosing a treatment for this patient ^[2-3].
In addition, the patient's metabolic disorders such as overweight, hypertension, and dyslipidemia suggest that GLP-1RA drugs can be used to complement insulin
.
Based on the above points, we need to choose a treatment plan for patients that can not only achieve the hypoglycemic effect of basal + mealtime insulin regimen, but also meet the GLP-1RA component supplementation, and then we think of innovative drugs
such as basal insulin GLP-1RA injection.

In evidence-based medicine, IDegLira regimens have a lower risk of hypoglycemia and weight benefit
compared with basal-mealtime insulin regimens with similar glucose-lowering efficacy.
Randomized controlled studies have shown ^[4] that switching basal insulin+OAD regimens to IDegLira regimens is similar to switching to basal-mealtime insulin regimens (HbA_1c reduction of 1.
5% in both groups).
However, the incidence of severe or confirmed symptomatic hypoglycemia was reduced by 89% in the IDegLiera group and by 92%
in the nocturnal hypoglycemia.
The real-world study EXTRA ^{study [5]} showed that after 6 months of conversion to the IDegLiga regimen with OAD combined with multiple daily insulin injection regimens, patients had a significant decrease in HbA1c levels (0.
7%, p<0.
0001)</b116> The incidence () (p<0.
0001) from baseline<b121>, and the average body weight of patients decreased by 2.
4 kg (

Medical profession

After a patient with 22U insulin glargine U100 for poor blood sugar control, you were given 16 doses of IDegLira (16 U insulin degludec and 0.
6 mg liraglutide) for conversion therapy, are you concerned about the occurrence of uncontrollable blood sugar? What are your thoughts on this?

Director Li Sheli:

First, after switching to the IDegLira regimen, we gave the patient a 16-dose starter, which was based on the recommendations in the drug label
.
The IDegLira label ^[8] suggests that switching to IDegLira from any insulin therapy containing basal insulin components is recommended to start
at 16 doses.
In the DUAL II global [⁹] and DUAL II China [10] studies, the baseline basal insulin dose was 20-40 U and 20-50 U, respectively, and the conversion IDegLira was based on ¹⁶ doses as the starting dose
.
In the DUAL II global study, after 26 weeks of switching to the IDegLara regimen, the average HbA_1c dropped to less than 7.
0 percent, resulting in a lower risk of hypoglycemia and weight benefit ^[9].
In DUAL II China, after 26 weeks of treatment with IDegLira, compared with Degludec insulin, T2DM patients had better control of HbA 1c, FPG, SMBG 9-point blood glucose spectrum, and the average PPG increase was lower, reaching HbA_1c<7% The proportion of patients without concurrent hypoglycemia and weight gain is higher, and the daily dose of insulin is lower ^[10].
The above results suggest that switching from different doses of basal insulin to IDegLira 16 and then adjusting the dose based on the individualization of the patient is beneficial for diabetes management
.

After switching treatment regimens for patients, we closely monitor blood glucose so that IDegLira doses
can be adjusted in a timely manner.
The Chinese Guidelines for the Prevention and Treatment of Type 2 Diabetes (2020 Edition) ^[11] recommends that the FPG target of most adults with T2DM is 4.
4~7.
0mmol/L, and we can adjust the dose in a timely manner based on this goal
.
If the patient's FPG is above the individualized target, the dose is adjusted upwards by 2 doses; If it is below the target value, the dose is lowered by 2; If the target value has been reached, the dose remains unchanged ^[8].
After one week of using IDegLira, the FPG reached 6.
6mmol/L, and then continued to steadily decrease to 5.
5mmol/L, which has reached the target value, so we did not adjust the dose during the
treatment.

In addition, when switching treatment options for patients, we also need to be alert to the risk of
gastrointestinal adverse effects.
The content of liraglutide in 16 doses of IDegLira is 0.
6 mg, and at this regimen dose, the risk of gastrointestinal adverse reactions is low and there is no need to worry too much
.
We see that in this case, the patient only showed symptoms of gastrointestinal-related adverse effects at initiation and the first week of application, and subsequent symptoms disappeared, indicating good
tolerability.

The switch from insulin glargine 22U to IDegLira 16 dose initiation regimen proved appropriate for this patient, who benefited greatly
.

Expert biographyProfessor
Li Sheli

Chief physician, master tutor
Director of Department of Endocrinology and Metabolism, Affiliated Hospital of Yan'an University
Chairman of Diabetic Foot Disease Branch of Shaanxi Health Promotion and Education Association
Member of the Standing Committee of Shaanxi Endocrinology Branch
Vice Chairman of the Endocrinology Branch of Shaanxi Sexual Society
Vice Chairman of the Obesity Professional Committee of Shaanxi Health Care Association
Vice Chairman of Child Growth and Development Committee of Shaanxi Health Care Association
Vice Chairman of the Adolescent Medicine Branch of Shaanxi Medical Association
Chairman of Yan'an Endocrine Society
Member of the Standing Committee of the Endocrinology and Diabetes Branch of the Bethune Spiritual Research Association
Member of the expert group of Shaanxi Endocrine Disease Diagnosis and Treatment Quality Control Center

References[1]Expert consensus on short-term intensive insulin therapy for type 2 diabetes, writing committee.
Chinese Journal of Diabetes,2022,14(01):21-31 [2] Lin Yi.
Drug Evaluation,2014,11(09):45-48 [3]Shafiee G, Mohajeri-Tehrani M, Pajouhi M, et al.
J Diabetes Metab Disord, 2012, 11(1): 17.
[4]Billings L K, Doshi A, Gouet D, et al.
Diabetes Care, 2018, 41(5): 1009-1016.
[5].
Price H, et al.
Diabetes Obes Metab.
2018 Apr; 20(4):954-962.
[6]Linjawi S, et al.
Diabetes Ther.
2017; 8(1):101-114.
[7]Lingvay I, et al.
JAMA.
2016; 315(9):898-907.
[8] IDegLira instructions[9] Buse J B, Vilsbøll T, Thurman J, et al.
Diabetes Care,2014,37(11):2926-2933.
[10]Pei Y,Agner B R,Luo B,et al.
Diabetes Obes Metab,2021,23(12):2687-2696.
[11] Diabetes Branch of Chinese Medical Association.
Chinese Journal of Diabetes ,2021,13(4):315-409

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