By Nicole MacKee
Early combination therapy with vildagliptin and metformin may provide greater and more durable blood glucose control for people newly diagnosed with type 2 diabetes than sequential metformin monotherapy, new research shows.
A randomised, double-blind, industry-funded trial published recently in the The Lancet – the Vildagliptin Efficacy in combination with metfoRmIn For earlY treatment of type 2 diabetes (VERIFY) trial – compared initial combination therapy (metformin plus the dipeptidyl peptidase-4 inhibitor, vildagliptin) with initial metformin monotherapy and placebo, adding vildagliptin only after treatment failure.
Treatment failure was defined as an HbA1c of at least 53 mmol/mol (7.0%) at two consecutive visits, 13 weeks apart. The researchers followed 2000 people (aged 18 to 70 years) who had been diagnosed with type 2 diabetes (with mild hyperglycaemia, HbA1c 48 to 58 mmol/mol or 6.5 to 7.5%) within the previous two years.
The researchers found a significant reduction in the relative risk for time to initial treatment failure in the early combination treatment group compared with the metformin monotherapy group over five years (hazard ratio, 0.51).
Median time to treatment failure in the monotherapy group was 36 months, the researchers found, while the time to treatment failure in the early combination therapy group could not be estimated beyond the 60-month study period.
The researchers further noted that both treatment approaches were safe and well tolerated.
But Professor Jenny Gunton, Head of the Centre for Diabetes, Obesity and Endocrinology Research and Professor of Medicine at the University of Sydney’s Westmead Clinical School, said the findings may have limited applicability in Australia.
She said the study showed that treating patients with both agents early on resulted in lower rates of ‘treatment failure’.
‘If you add on the vildagliptin to the metformin after treatment failure, the failure rate is still lower, of the order of 7 to 8% of people,’ Professor Gunton told Endocrinology Today. ‘It is that group of 7 to 8% [of patients] that is interesting. Whether it is worth treating lots of people for that 7 to 8%, and how long that lasts, is not clear.’
Professor Gunton noted that to be eligible for PBS-subsidised gliptins in Australia, patients needed to have an HbA1c greater than 7% despite treatment with metformin or a sulfonylurea.
‘The trial patients had lower HbA1c than that at the start of the study (median baseline HbA1c 6.7%, with more than 70% of participants under that 7% cut off). Once you treat the people with metformin, their HbA1c would be under 7% in all people who could take the metformin, so [these findings] would not have wide applicability to Australia.’
Lancet 2019; https://doi.org/10.1016/S0140-6736(19)32131-2.