"First evidence" supports precise treatment of type 2 diabetes, and research reveals differences in hypoglycemic response in patients with different characteristics

▎ WuXi AppTec content team editor In the treatment of type 2 diabetes, life>
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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
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A study recently announced at the European Association for the Study of Diabetes (EASD) 2021 meeting added important evidence for this
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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
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Screenshot source: Reference [3] 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
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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
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Pioglitazone is more effective in patients with BMI>30 kg/m2, while sitagliptin is more effective in patients with BMI<30 kg/m2; in patients with better renal function, canaglitazone has a better hypoglycemic effect ; And for those with mildly decreased renal function, sitagliptin is more suitable
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"This is the first evidence to support precision medicine for type 2 diabetes
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We have proved that by dividing patient subgroups by clinical criteria, certain drugs will have more advantages
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"The lead investigator, Professor Andrew Hattersley of the University of Exeter, UK, said
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He also reminded, "These results do not mean that all patients with a BMI> 30 should use pioglitazone, or that all patients with mildly decreased eGFR All patients should use DPP-4 inhibitors
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The choice of medication also needs to consider factors other than blood sugar
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For example, patients with heart failure, cardiovascular disease and chronic kidney disease can prefer SGLT2 inhibitors
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"Unique trial design, each patient is their own control TriMaster is a phase 4, multicenter, randomized, double-blind, 12-month crossover trial
.
The
study included 525 type 2 diabetes patients, these patients Between 30-79 years old, taking metformin monotherapy or metformin or combined with sulfonylureas did not reach the target blood glucose level (7.
5%＜HbA1c＜12.
2%)
.
The
patients were based on the original treatment plan in a random order (3 drugs There are 6 orders in total, one of which is randomly assigned.
) Increase pioglitazone, sitagliptin, and canagliflozin for 16 weeks each time
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During the study, patients were unaware of the specific drugs taken at each stage
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Therefore, The medications of each patient at each stage can be used as their own mutual comparison
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The
effects of the drugs in different patient groups are different.
A total of 458 patients have completed all three medication phases
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Overall, there was no difference in the blood glucose reduction rate between the three therapies, and the average HbA1c was reduced from baseline 8.
9% to about 7.
5%-7.
6%
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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)
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After further stratifying the patients, the difference became apparent
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For patients with different BMI: BMI>30 kg/m2: pioglitazone is more effective in lowering blood sugar, HbA1c is 0.
13% lower than sitagliptin group (1.
48 mmol/mol); BMI<30 kg/m2: sitagliptin is more effective Hypoglycemic, HbA1c was 0.
14% (1.
44 mmol/mol) lower than that in the pioglitazone group
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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% lower than that in sitagliptin group (1.
08 mmol/mol); a slight decrease in renal function (eGFR is between 60 ml/min/1.
73m2-90 ml/min/1.
73m2): sitagliptin is more effective in reducing blood sugar, HbA1c is compared with canagliflozin group 0.
16% (1.
74 mmol/mol) lower
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"Therefore, if we treat different subgroups of patients with more suitable drugs, this will bring about a 0.
27% (3 mmol/mol) reduction in HbA1c compared to treatment with other drugs
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" The research team pointed out
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Image source: 123RF In terms of safety, each drug has its own advantages and disadvantages
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Pioglitazone: better tolerated, but causes most people to gain weight
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Sitagliptin: has the least side effects, but is relatively poorly tolerated, causing more people to stop the drug
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Canagliflozin: Most suitable for weight control, but patients report many side effects
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There is no significant difference in the risk of hypoglycemia between different drugs
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The preferences of all patients for the three drugs are also relatively average
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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
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Patient preference is mainly related to hypoglycemic effect and side effects
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Future exploration Caroline M.
Kistorp, professor of endocrinology at the University Hospital Copenhagen, said that in 2015 when the study was launched, “precision medicine research was conducted in patients with type 2 diabetes through randomized clinical trials rather than retrospective analysis.
It was very cutting-edge at the time
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" 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
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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
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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
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There must be many tool choices in the doctor’s toolbox
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And I still think that some patients are right.
Pioglitazone reacts well
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"In addition, due to the early launch of the trial, this trial did not analyze the results of cardiovascular disease
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After the launch of this trial, the landmark EMPA-REG OUTCOME trial and more studies in recent years have revealed that most SGLT2 inhibitors cardiovascular disease benefit
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Professor Hattersley said that the future will explore cardiovascular outcomes data analysis; in addition, for selected patients prefer drugs in the study, long-term follow-up will continue
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"Overall, the patient's full The doctor approves of their choice preference
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We will see if the patient still has a good drug response and tolerance
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"I look forward to more exploration and accumulation of evidence, so that the concept of precision treatment can be better applied to common chronic diseases such as diabetes
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Related reading "The Lancet" blockbuster! Diabetes treatment concept change: weight control should be the primary treatment goal! Combined with metformin, what is the difference in the effects of the four common hypoglycemic therapies? ADA has published two "Lancet and Longest" studies: once a week, better than insulin! Type 2 Diabetes Dual Mechanism New Drug Metabolism Benefits Extensive "Lancet" Sub-Journal depth: These innovative therapies are expected to change the future reference materials for the treatment of Type 2 Diabetes [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:// 959307[3] 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/Disclaimer: WuXi AppTec's content team focuses on introducing global biomedical health research progress
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If you need guidance on treatment plans, please go to a regular hospital for treatment
.