"Sugar Control Tool" has been approved for new indications again!

*For medical professionals to read only for reference.
Insulin therapy is one of the important methods of blood glucose management for diabetic patients.
It has a good effect on lowering blood sugar.
It is a commonly used hypoglycemic drug for long-term disease and hospitalized patients.
The risk of weight gain [1].

Moreover, many patients need to receive other oral hypoglycemic drugs when using insulin, so that blood sugar levels can be more fully controlled [2].

For such patients, the choice of oral hypoglycemic agents should try to avoid the occurrence of hypoglycemia in the patient, and comprehensively consider the patient's heart, liver and kidney conditions, weight gain and compliance and other important factors.

Insulin’s official “new partner” hypoglycemic drug dipeptidyl peptidase-4 inhibitor (DPP-4i) can increase endogenous glucagon-like peptide-1 (GLP-1) levels, enhance insulin secretion, and inhibit Glucagon secretion.
Studies have shown that, compared with insulin therapy alone, the treatment of patients with DPP-4i combined with insulin can further improve blood glucose control without increasing the risk of hypoglycemia and weight gain [3].

Linagliptin is a non-peptidomimetic, a highly selective DPP-4 inhibitor, which was approved for marketing in China in 2013.
The previously approved indications were monotherapy, combined metformin, combined metformin and sulfonylureas Class drugs are used in the treatment of type 2 diabetes.

Recently, linagliptin combined with insulin therapy (with or without metformin), a new indication for improving blood glucose control in patients with type 2 diabetes based on diet and exercise has been approved by the National Food and Drug Administration (NMPA).

The approval of new indications has been “a long-planned” 2013 study confirmed that basal insulin combined with linagliptin treatment can improve blood sugar control, improve body weight, and reduce insulin consumption [4].

A total of 1261 patients with HbA1c between 7.
0% and 10.
0% were included in the study. On the basis of basal insulin combined with or without metformin and/or pioglitazone, patients were randomly divided into a combined linagliptin (5 mg once a day) group or a placebo group [4].

After 24 weeks, the linagliptin group could reduce HbA1c by 0.
65% compared with the placebo group.
This advantage continued to the end of the 76-week follow-up (Figure 1).
At 52 weeks of follow-up, the insulin consumption in the linagliptin group was reduced by 1.
6 IU/day ( 2.
6 vs.
4.
2IU/day, P<0.
003), weight loss was 0.
26kg [4].

 Figure 1 The combination of basal insulin and linagliptin reduces blood sugar more significantly.
Similar results were obtained in subsequent studies.
In a clinical phase IV, multi-center, randomized, double-blind, placebo-controlled study [5], 302 cases were included About 75% of elderly patients with T2DM who are ≥60 years old and receive stable doses of insulin therapy have a disease course of more than 10 years.
The patients receive linagliptin (n=151) or placebo (n=151) on the basis of the original treatment regimen (patients HbA1c baseline is 8.
2%).

 The 24-week follow-up results showed that compared with patients in the placebo group, the decrease in HbA1c in the insulin + linagliptin group from baseline decreased by 0.
63% (-1.
01% vs.
-0.
38%, P <0.
001), a significant increase The blood glucose compliance rate (Figure 2, Figure 3) [5].

 Figure 2 HbA1c changes from baseline Figure 3 HbA1c compliance rate In terms of safety, there was no significant difference in the incidence of any hypoglycemia between the two groups (34.
4% vs.
25.
8%); moreover, the linagliptin group had blood glucose standards without hypoglycemia The proportion of patients was significantly higher than that of the placebo group (Figure 4) [5].

It can be seen that in elderly type 2 diabetic patients receiving stable insulin therapy, the addition of linagliptin can improve blood sugar control and increase the high-quality compliance rate (HbA1c<7% and no hypoglycemia) [5].

Figure 4 The proportion of patients with HbA1c reaching the standard and without hypoglycemia.
A study published by Japanese researchers in 2019 showed that the blood glucose of patients in the linagliptin combined with insulin group continued to decrease steadily.
At 52 weeks, the patient's HbA1c decreased by 0.
86% (patient HbA1c baseline was 8.
07%), compared with the placebo group (receiving only basal insulin therapy), HbA1c decreased by 0.
58% (P<0.
0001) (Figure 5), and there were no new adverse safety events [6].

Figure 5 Changes in HbA1c over time during the 1-year follow-up.
In addition, in hospitalized patients with type 2 diabetes, insulin combined with DPP-4i linagliptin also performed outstandingly, a multi-center, observational real-world study [7 ], included inpatients with non-cardiac surgery type 2 diabetes who received basal-meal insulin therapy, and matched patients who received linagliptin + basal insulin therapy.
The results of the study suggest that compared with the basal-meal insulin regimen, Linagliptin-basal insulin has the same hypoglycemic effect, while significantly reducing the total daily dose of insulin (22.
8±7.
5 vs.
32.
5±5.
2 U/d) and the number of daily insulin injections (2.
6±0.
8 vs.
4.
0±0.
0) Times/day) (P＜0.
001), reducing the incidence of hypoglycemia (8.
1 vs.
16.
4 times/100 patients·year, P＜0.
001).

 Linagliptin, which has undergone a lot of evidence-based tests, has been approved by the U.
S.
Food and Drug Administration (FDA) and the European Medicines Agency (EMA) before the NMPA is approved for combined insulin therapy with or without metformin.

Cardiovascular, liver, and kidney safety are guaranteed.
Diabetic patients who use insulin have a relatively longer course of disease and are older.
Such patients usually have more complicated diseases, complicated medications, or accompanied by a certain degree of liver and kidney damage, and require higher The security requirements of [8-10].

Linagliptin in DPP-4i is rarely metabolized by CYP450 enzymes in the liver, and there are few drug interactions.
It is currently the only DPP-4i that does not need to adjust the drug dose according to the patient's liver and kidney function status [11].  It has also been observed in previous studies that linagliptin also has strong evidence-based evidence in terms of cardiorenal safety that is of special clinical concern, such as the well-known cardiovascular safety outcome study (CVOT) CARMELINA study and CAROLINA study.
, Linagliptin did not increase the risk of heart and kidney damage and the risk of hospitalization due to heart failure [12-13].

 Summary In the face of the combined use of insulin and oral drugs, evidence-based evidence has confirmed that combined with linagliptin can significantly improve blood sugar levels and is safe and well tolerated, without increasing the risk of hypoglycemia and weight gain.

Moreover, linagliptin has good cardiovascular, liver, and kidney safety.
Its once-a-day administration can improve patient compliance, and it forms an "ideal CP" with insulin.
Now this combination program has been officially approved by the NMPA.
It is believed that it will It will bring greater convenience and benefits to doctors and patients.

PC-CN-102241, valid until March 18, 2022.

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[11] Chinese Medical Doctor Association Endocrinology and Metabolism Physician Branch.
Chinese Journal of Endocrinology and Metabolism.
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[12] Rosenstock J et al.
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[13] Rosenstock J, et al.
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[14]Rosenstock J, et al.
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