Allowing people with type 2 diabetes to try agents from three different classes of antidiabetes drugs showed they usually find a clear preference, often the drug that gives them the best glycemic control and least bothersome adverse effects, according to secondary findings from a randomized study of patients in the United Kingdom.
“This is the first study in which the same patient has tried three different types of glucose-lowering drug, enabling them to directly compare them and then choose which one is best for them,” Andrew Hattersley, BMBCh, DM, the study’s principal investigator, said in a written statement. “We’ve shown that going with the patients’ choice results in better glucose control and fewer side effects than any other approach. When it’s not clear which drug is best to use, then patients should try before they choose. Surprisingly, that approach has never been tried before.”
Mitchel L. Zoler/MDedge News
Dr. Andrew Hattersley
These secondary results from the TriMaster study were recently published in Nature Medicine and presented at the annual meeting of the European Association for the Study of Diabetes (EASD) in September, as reported by this news organization.
TriMaster enrolled adults aged 30-80 years with a clinical diagnosis of type 2 diabetes for at least 12 months. Their glycemia was inadequately controlled despite treatment with metformin alone or two classes of oral glucose-lowering therapy that did not include an agent from any of the three classes tested in the study: dipeptidyl peptidase–4 (DPP-4) inhibitors, sodium-glucose cotransporter 2 (SGLT2) inhibitors, and thiazolidinediones. The people taking two different drug classes at entry were most often taking metformin and a sulfonylurea.
Do BMI and renal function affect treatment response?
TriMaster tested two hypotheses. Firstly, would people with a body mass index of more than 30 kg/m2 have greater glucose lowering with the thiazolidinedione pioglitazone (Actos) than with the DPP-4 inhibitor sitagliptin (Januvia), compared to people with a lower BMI?
Secondly, would people with an estimated glomerular filtration rate (eGFR) of 60-90 mL/min/1.73 m2 have greater glucose lowering with sitagliptin than with the SGLT2 inhibitor canagliflozin (Invokana), compared with people with higher levels of renal function? The metric for both hypotheses was change in A1c levels from baseline.
The study included 525 adults with type 2 diabetes in a double-blind, three-way crossover trial that assigned each participant a random order of serial 16-week trials of treatment with sitagliptin 100 mg once daily, canagliflozin 100 mg once daily, and pioglitazone 30 mg once daily, with each agent added to the preexisting background regimen.
Analysis showed that for second- or third-line therapy in people with type 2 diabetes “simple predefined stratification using BMI and renal function can determine the choice of the drug most likely to be effective for glucose lowering,” the researchers concluded.
Among those with a BMI of more than 30 kg/m2, patients achieved a lower A1c on pioglitazone, compared with sitagliptin, while those with a lower BMI had their best A1c response on sitagliptin. Patients with impaired renal function (eGFR 60-90 mL/min/1.73 m2) had better A1c lowering with sitagliptin, while those with a higher eGFR had better A1c lowering with canagliflozin.
These results appeared in a second article published in Nature Medicine, and the researchers also presented these findings at the EASD 2021 annual meeting, as reported by this news organization at the time.