Not sure which therapy is best? Let the patient choose!

Analysis of a patient-preference study revealed its efficacy for people with type 2 diabetes at the latest EASD Annual Meeting. Lisa Buckingham reports.

Recent guidelines from the ADA/EASD have emphasised the importance of a patient-centred approach to type 2 diabetes treatment, said Beverley Shields, a statistician from the University of Exeter. She highlighted the section about shared decision making and the need to seek patient preference.

She was presenting on patient preferences for type 2 diabetes therapy in the TriMaster trial. The main findings were presented last year, but these were the results of additional analysis of patient preference.

We know that treatment decisions need to balance likely benefits versus adverse effects. Patients vary in their glycaemic response and the side-effects they experience with different drugs, and this cannot be predicted beforehand. The priorities of patients will also vary, with some wanting to lower their glucose while others emphasise wanting to avoid weight gain and hypos.

Most of the information we have on therapies, she said, is from parallel group trials, which help determine at population level what the average response is but they don’t help at an individual level to work out which drug will work best for a specific patient.

The alternative are ‘n-of-1’ trials or crossover trials, where each individual receives multiple alternative therapies, so we can see within-person comparisons. The person can also compare their own lived experience on each drug to establish which they prefer.

The aim of their study was to use this approach to examine patient preference in a randomised, three-way, double-blind, crossover trial of second/third line therapies in type 2 diabetes.

They recruited patients with type 2 diabetes treated with either metformin or metformin and sulphonylureas and with HbA1c of 58-110 mmol/mol, and randomised them into one of six drug order sequences. The drugs used were pioglitazone, sitagliptin and canaglaflozin. Participants completed 16 weeks on each drug with a four-week washout period in between. At the end of each drug period, weight and HbA1c were measured and participants reported any side-effects.

At the end of the trial, the 457 patients who’d completed all three drugs were asked to rank the three drugs they’d tried in order of preference. They were asked to do this twice – once before they’d been given the results of their HbA1c and weight and again afterwards. The cohort was predominantly male (74%) with a median age of 61 and 95% were of white ethnicity.

Mean HbA1c was very similar across all three drugs; pioglitazone had the lowest rate of non-tolerability at 5%, compared with 8.3% for sitagliptin and 7.7% for canagliflozin. Sitagliptin had the lowest number of side-effects at 1.30, compared with 1.59 for pioglitazone and 1.66 for canagliflozin. Canagliflozin was associated with the lowest weight on average, 91.1 kg compared with 93.4 for sitagliptin and 94.9 for pioglitazone.

When patients were asked to rank the drugs before they were aware of their results, 24% chose pioglitazone, 33% chose sitagliptin and 37% chose canagliflozin, with the remaining 6% having no preference.

The predominant reason that patients said they had chosen their preferred drug was that it was the ‘one they felt better on’.

After they had been given their results and chose again, pioglitazone came in at 25%, sitagliptin at 35% and canagliflozin at 38% with 2% having no preference, so fairly similar results to beforehand, but 125 (28%) of patients changed their minds after being given their results. The majority stated that they changed their preference because of the HbA1c result, although reasons differed between drugs with, for example, weight loss being the biggest reason that people chose canagliflozin.

When they looked at the characteristics of people based on their preferred drug, those who had the lowest HbA1c on pioglitazone had chosen pioglitazone as their preferred drug and the same applied for the other two therapies. The same association was seen with side-effects. However, weight seemed to be less of a factor in their decision-making. Regardless of which drug they preferred, patients had the highest weight on pioglitazone and the lowest on canagliflozin.

The advantage to this study, said Beverley, was that they could look at within-person differences. For example, if they’d treated everyone with canagliflozin because that was preferred most on average, they wouldn’t have had as many patients treated with the drug that was best for them in terms of HbA1c and side-effects. The results highlight the importance of taking into account patient preferences and not just making inferences from the mean of the population.

In summary:

• Patients tend to prefer the drug they felt better on, with the lowest HbA1c and fewest side-effects
• Weight was less important to patients when choosing their preferred treatment
• Allocating each individual’s preferred drug compared with the overall preferred drug (canagliflozin) results in patients receiving the drug that results in the lowest HbA1c and side-effects for them

On the basis of this, she said, they propose that a short trial of alternative possible therapies is the optimal way to assess individual preference and that we should let the patient choose.

In the post-presentation questions, she was asked if they’ll work on prediction models based on patients’ characteristics because clinicians will be trying to predict which therapy will be best before it’s started. She responded by saying that the main hypotheses of TriMaster was predicting which characteristics predict response. They found that body mass index and estimated glomerular filtration rate, for example, were able to help predict response and these are results that they will be submitting for publication in the near future. Prediction models are one of the routes we can choose, she said, but the option of allowing patients to try multiple therapies is a good option and one which patients seemed to really like.

She also went back to the issue of weight change and pointed out that many of the studies on patient preference state that weight change is a priority, but it’s often posed as a hypothetical question. They have now seen with this lived-experience study that weight was not the highest priority.

Any opinions expressed in this article are the responsibility of the EASD e-Learning Programme Director, Dr Eleanor D Kennedy.