75% reduction in the number of injections!

Good news is coming for patients with type 2 diabetes who need several insulin injections a day.

Recently, the team of Dario Giugliano from the University of Campania, Italy published important research results in the journal Diabetes Care [1].

They found that those with type 2 diabetes who received four insulin injections a day (one basal insulin + three pre-meal insulin), if the pre-meal insulin is replaced by an SGLT2 inhibitor, or a mixed injection of insulin + GLP-1RA is completely replaced The original treatment plan can achieve the same glucose control effect and significantly reduce the risk of hypoglycemia.

In other words, after changing the dosing regimen, the number of insulin injections will be changed from 4 to 1 and the same effect can be achieved.

This is really happy.

Screenshot of the paper's homepage Speaking of diabetes and hypoglycemic, what drugs will come to mind? Is it a variety of insulin injections, is it the SGLT2 inhibitor that has emerged in recent years, is it GLP-1RA, which is both weight loss and blood sugar reduction, or our "old friends" metformin and acarbose? In this era of "century magical medicine" and a dazzling array of new hypoglycemic drugs, how to better use and match these eighteen magical treasures to benefit the majority of sugar lovers has become one of the hotspots of clinical research today.

Studies have shown that a quarter of type 2 diabetes patients are now using insulin, and only 50% of patients with glycosylated hemoglobin meet the standard (HbA1c <7%) [2, 3].

For patients who use insulin but blood sugar is not up to standard, we usually increase the dose of insulin or the frequency of insulin administration before meals to enhance the efficacy.

However, as the intensity and complexity of treatment options increase, patients' compliance will decrease, and they will also face more adverse reactions, such as hypoglycemia and weight gain.

Therefore, once a day or once a week GLP-1RA injections and once a day oral SGLT2 inhibitors are two new types of hypoglycemic agents that do not gain weight, have low risk of hypoglycemia, simple dosing regimens, and can effectively reduce postprandial blood sugar.
Medicine has received widespread attention in recent years.

The guidelines published by the American Diabetes Association pointed out that for patients who use more than 0.
5 IU/kg of basal insulin per day but HbA1c does not meet the standard, they can choose to add pre-meal insulin or GLP-1RA to the treatment plan [4].

So, can SGLT2 inhibitors, which have similar advantages, be on the same level as pre-meal insulin? For patients with multiple insulin injections per day, is it feasible and effective to convert pre-meal insulin to GLP-1RA or SGLT2 inhibitors? The Giugliano team recruited 305 patients with type 2 diabetes over the age of 35 who received four insulin injections a day, but whose HbA1c was still higher than 7.
5%.

The subjects were randomly and equally allocated to the basal-bolus insulin group (BBI, basal-bolus insulin), the basal insulin+SGLT2 inhibitor group (BI+gliflozin), and the basal insulin+GLP-1RA mixture group (BI+GLP) -1RA).

Patients in the BI+gliflozin group were further randomly assigned to the gliflozin, empagliflozin, and canagliflozin treatment groups; patients in the BI+GLP-1RA group were evenly assigned to IGlarLixi (insulin glargine and gliflozin) Cinatide mixed injection) and IDegLira (degulin and liraglutide mixed injection) treatment group.

In the 6-month trial, patients can adjust their insulin doses under the guidance of their doctors based on their self-tested blood glucose levels.

There is no significant difference in the various baseline indicators of the three groups of subjects in the experiment flow chart: the patients have an average history of diabetes for 17 years, the daily required insulin dose is about 50 IU, and the average HbA1c is between 8.
5-8.
7%.

A comparative study on the changes of various indicators in each group at the 6th month of treatment found that in the 6th month of the trial, the HbA1c of the patients in each group was significantly reduced by about 0.
6-0.
7, but there was no significant difference between the groups. There was no significant difference in the proportion of patients with HbA1c reaching ≤7.
0%, ≤7.
5%, and ≤8.
0% in each group.
That is to say, the three treatment options are comparable in efficacy.

However, because the BI+Gliflozin and BI+GLP-1RA groups replaced the original three-day pre-meal insulin with a once-a-day injection or oral tablet, the daily insulin dose and the number of injections of the two groups were significantly lower than those of the BBI group.

Comparison of the proportion of patients with HbA1c≤7.
0%, ≤7.
5%, and ≤8.
0% in each group at the 6th month of treatment.
The researchers also used questionnaires to quantify the subjects’ satisfaction with the treatment and found that during the 6-month treatment , The satisfaction of patients in the BBI group was basically the same, while the satisfaction of the other two groups was significantly improved.

In terms of adverse reactions, the performance of the two simplified treatment options is also remarkable.

Compared with the BBI group, the risk of hypoglycemia in the BI+Gliflozin and BI+GLP-1RA groups was significantly reduced.

The risk of hypoglycemia in each group of patients was 7.
8% (BI+GLP-1RA), 5.
9% (BI+Gliflozin), and 17.
8% (BBI).

However, it should be pointed out that in the BI+GLP-1RA group and BI+Gliflozin group, 4 and 3 subjects respectively terminated the trial due to adverse reactions.
The main reason was the gastrointestinal side effects caused by GLP-1RA.
And genital fungal infections caused by SGLT2 inhibitors, these are also common clinical adverse reactions.

Therefore, the old saying is that drugs are three-point poison, and GLP-1RA and SGLT2 inhibitors are not harmless.

In the 6th month of treatment, the total daily dose of insulin and the number of daily injections in each group of patients were compared.
In general, this 6-month clinical trial provides multiple possibilities for simplifying insulin treatment regimens.

Although the two mixed injections IGlarLixi and IDegLira used in the trial are not commonly used clinically, it is not difficult to predict that the basal insulin + GLP-1RA after the mixed components will have a similar effect.

In addition, a large number of recent studies have also found that some GLP-1RA and SGLT2 inhibitors can reduce the risk of cardiovascular disease, and SGLT2 inhibitors can also alleviate the progression of heart failure and chronic kidney disease [4, 5].

Therefore, for patients with diabetes complicated with cardiovascular disease, heart failure or kidney disease, this simplified treatment plan may have a benefit of 1+1>2.

However, the fly in the ointment is that due to the short time and single sample size, this clinical trial itself has many limitations.

We also look forward to more long-term, large-sample, and multi-center related trials in the future~ Reference 1.
Giugliano D, Longo M, Caruso P, et al.
Feasibility of Simplification From a Basal-Bolus Insulin Regimen to a Fixed-Ratio Formulation of Basal Insulin Plus a GLP-1RA or to Basal Insulin Plus an SGLT2 Inhibitor: BEYOND, a Randomized, Pragmatic Trial [published online ahead of print, 2021 Apr 21].
Diabetes Care.
2021;dc202623.
2 Lipska KJ, Yao X, Herrin J, et al.
Trends in drug utilization, glycemic control, and rates of severe hypoglycemia, 2006-2013.
Diabetes Care 2017; 40:468–4753.
Montvida O, Shaw J, Atherton JJ, Stringer F, Paul SK.
Long-term trends in antidiabetes drug usage in the US: real-world evidence in patients newly diagnosed with type 2 diabetes.
Diabetes Care 2018;41:69–784.
American Diabetes Association.
9.
Pharmacologic Approaches to Glycemic Treatment:Standards of Medical Care in Diabetes-2021.
Diabetes Care.
2021;44(Suppl 1):S111-S124.
American Diabetes Association.
10.
Cardiovascular Disease and Risk Management: Standards of Medical Care in Diabetes-2021.
Diabetes Care.
2021; 44(Suppl 1):S125-S150.
Chief EditorBioTalker