"First Evidence" Supports Research on Precision Treatment of Type 2 Diabetes Reveals Differences in Patients' Hypoglycemic Response

In the treatment of type 2 diabetes, life>
.

However, in the current second and third-line treatments, in addition to the drug recommendations for patients with high cardiovascular risk and chronic kidney disease in recent years, most patients choose which drugs to add, and there is a lack of "precise" individualized medication guidance

A study recently announced at the European Association for the Study of Diabetes (EASD) 2021 meeting added important evidence for this
.

This crossover test called TriMaster evaluated 3 different types of commonly used drugs in second/third-line treatment, including DPP-4 (dipeptidyl peptidase-4) inhibitor sitagliptin, SGLT2 (sodium-glucose synergy) Transporter 2) Inhibitors canagliflozin and thiazolidinedione pioglitazone

The results support that the clinical characteristics of patients combined with individual preferences can be used to guide the "precise" selection of type 2 diabetes drugs
.

In the study, although the overall blood sugar-lowering levels of the 3 drugs were similar, for patients with different body mass index (BMI) and different renal function levels (based on glomerular filtration rate [eGFR]), the blood sugar-lowering effects of different types of drugs Each effect has its own merits

Pioglitazone is more effective in patients with BMI>30 kg/m2, while sitagliptin is more effective in patients with BMI<30 kg/m2;

Patients with better renal function have better hypoglycemic effect of canagliflozin; while patients with mild renal function decline, sitagliptin is more suitable
.

"This is the first evidence to support precision medicine for type 2 diabetes
.

We have proved that certain drugs will be more advantageous by dividing patient subgroups by clinical criteria

He also reminded, "These results do not mean that all patients with BMI>30 should use pioglitazone, or that all patients with mildly decreased eGFR should use DPP-4 inhibitors
.

The choice of medication should also consider factors other than blood sugar

Unique trial design, each patient is his own control

Unique trial design, each patient is his own control

TriMaster is a 4-phase, multicenter, randomized, double-blind, 12-month crossover trial
.

A total of 525 patients with type 2 diabetes were included in the study.

On the basis of the original treatment plan, the patients took pioglitazone, sitagliptin, and canagliflozin in a random order (a total of 6 orders of 3 drugs, randomly assigned one) sequentially for 16 weeks
.

During the study, the patients were unaware of the specific drugs taken at each stage

Drugs have different effects in different patient groups

Drugs have different effects in different patient groups

A total of 458 patients completed all 3 medication phases
.

Overall, there was no difference in the blood glucose reduction rate between the three therapies, and the average HbA1c was reduced from baseline 8.

Before the start of the study, more than half (58%) of these patients were obese (BMI>30 kg/m2), and 52% had normal renal function (eGFR>90 ml/min/1.
73m2)
.
After further stratifying the patients, the difference became apparent
.

For patients with different BMI:

BMI>30 kg/m2: Pioglitazone is more effective in lowering blood sugar, HbA1c is 0.
13% lower than that of sitagliptin (1.
48 mmol/mol);

BMI<30 kg/m2: Sitagliptin is more effective in lowering blood sugar, and HbA1c is 0.
14% (1.
44 mmol/mol) lower than that in the pioglitazone group
.

For patients with different renal functions:

Normal renal function (glomerular filtration rate [eGFR]>90 ml/min/1.
73m2): Canagliflozin is more effective in reducing blood sugar, and HbA1c is 0.
10% (1.
08 mmol/mol) lower than that of sitagliptin ；

Slight decline in renal function (eGFR is between 60 ml/min/1.
73m2 – 90 ml/min/1.
73m2): sitagliptin is more effective in lowering blood sugar, and HbA1c is 0.
16% lower than that in the canagliflozin group (1.
74 mmol/ mol)
.

"Therefore, if we treat different subgroups of patients with more suitable drugs, compared with treatment with other drugs, this will bring about a 0.
27% (3 mmol/mol) reduction in HbA1c benefit
.
" The research team pointed out
.

In terms of safety, each drug also has its own advantages and disadvantages
.

Pioglitazone: better tolerated, but causes most people to gain weight
.

Sitagliptin: The side effects are the least, but the tolerance is relatively poor, causing more people to stop the drug
.

Canagliflozin: Most suitable for weight control, but patients report many side effects
.

There is no significant difference in the risk of hypoglycemia between different drugs
.

The preferences of all patients for the three drugs are also relatively average
.
After being reminded of their own blood sugar and weight changes, the results of the patients' choice of drug preference were: 25.
8% chose pioglitazone, 34.
8% chose sitagliptin and 38.
7% chose canagliflozin
.
Patient preference is mainly related to hypoglycemic effect and side effects
.

Future exploration

Future exploration

Caroline M.
Kistorp, professor of endocrinology at the University Hospital Copenhagen, said that in 2015 when the study was launched, “through randomized clinical trials rather than retrospective analysis, precision medicine research in patients with type 2 diabetes was Very cutting-edge
.
"

She also pointed out that with the continuous development of new drugs, GLP-1 receptor agonist drugs may be more worthy of attention than the thiazolidinedione drugs used in the trial
.
In this regard, Professor Hattersley explained that although it is an old drug, pioglitazone is still widely used around the world, and a more important consideration in the trial is that this is a class of drugs with different mechanisms, "there is a chance to see greater differential effects.
"After all, one of the important purposes of the trial is to confirm whether precision medicine works in type 2 diabetes
.

Dr.
Mikael Rydén, Honorary Secretary of EASD, further pointed out that “thiazolidinediones still have a place, although they are not suitable for patients with heart failure
.
There must be many tool choices in the doctor’s toolbox
.
And I still think that some patients are right.
Pioglitazone responds well
.
"

In addition, due to the early start of the trial, this trial did not analyze the results of cardiovascular disease
.
After the launch of this trial, the landmark EMPA-REG OUTCOME trial and more studies in recent years have revealed the cardiovascular benefits of most SGLT2 inhibitors
.

Professor Hattersley said that in the future, cardiovascular outcome data will be explored and analyzed; in addition, patients who have chosen their preferred drugs in the study will also continue long-term follow-up
.
"In general, the patient's general practitioner recognizes their choice preference
.
We will see if the patient still has a good drug response and tolerability
.
"

Reference

[1] TriMaster Study Shows Precision Medicine in Diabetes Is Possible.
Retrieved October 26, 21, from https:// EASD: Precision in Diabetes Management and Impact of COVID-19.
Retrieved October 26, 21, from https:// TriMaster.
Retrieved October 26, 21, from https:// TriMaster study: first foray into precision medicine.
Retrieved October 26, 21, from https://diabetesonthenet.
com/diabetes-primary-care/trimaster-precision-medicine/