A new study has become the first to show the long-term “durability” of early combination therapy in patients with newly diagnosed with type 2 diabetes.
It found early treatment with vildagliptin and metformin in newly diagnosed patients led to better long-term blood glucose control and a reduced rate of treatment failure than metformin alone.
Vildagliptin (Galvus and Zomelis) is an oral drug used to treat type 2 diabetes and belongs to the class of drugs known as dipeptidyl peptidase-4 (DPP-4) inhibitors.
By inhibiting this key enzyme, DPP-4 inhibitors promote secretion of insulin by the pancreas, and inhibit production of glucagon, and thus help control blood sugar and avoid hyperglycaemia.
“Early intervention with a combination therapy strategy provides greater and durable long-term benefits”
Currently, the first-line treatment recommended for type 2 diabetes is metformin monotherapy, with combination therapy only introduced later following treatment failure.
The new study, led by researchers at Oxford University, included 2,001 patients from 254 centres in 34 countries.
It saw 998 randomised to receive early combination therapy using vildagliptin and metformin, and 1,003 randomised to receive initial metformin alone, across a five-year treatment period.
The VERIFY (Vildagliptin Efficacy in combination with metfoRmIn For earlY treatment of type 2 diabetes) study was divided into three periods.
In period 1, patients received either the early combination treatment with metformin and vildagliptin 50mg twice daily, or initial metformin monotherapy and placebo twice daily.
Treatment response was monitored by patients visiting their centre every 13 weeks, when the patients’ HbA1c level was assessed.
If the initial treatment failure, patients in the metformin group received vildagliptin 50mg twice daily in place of the placebo and those in the early combination therapy group continued on combination.
Subsequent failure was assessed as an end-point for second failure by two further visits with loss of glycaemic control. Physicians would then move patients onto insulin therapy.
However, patients who did not fail in period 1 but maintained good glycaemic control, continued administration of their randomised study medication for up to five years.
The primary endpoint was the time from randomisation to initial treatment failure, defined as HbA1c measurement of at least 53 mmol/mol at two scheduled visits, 13 weeks apart, during period 1.
A total of 1,598 patients completed the five-year study, 811 in the early combination therapy group and 787 in the monotherapy group.
The incidence of initial treatment failure during period 1 was 43·6% of patients in the combination treatment group and 62·1% of patients in the monotherapy group.
The median observed time to treatment failure in the monotherapy group was 36.1 months and for those receiving early combination therapy was estimated to be around 61.9 months.
The risk of losing blood glucose control was approximately halved in the early combination treatment group compared with the monotherapy group over the five-year study duration.
During period 2, when patients in both groups were receiving combination treatment, the relative risk of losing blood glucose control was also reduced by 26% among those receiving the early combination treatment, compared with those who transferred to it after their first treatment failure.
The researchers said the results showed that the early combination therapy strategy approach was superior to a sequential strategy approach.
They suggested the better long term “durability” of blood glucose control seen in the combination group could be due to the complementary mechanism of action between the two drugs.
The findings were presented at this year’s Annual Meeting of the European Association for the Study of Diabetes (EASD) in Barcelona and published simultaneously in The Lancet.
The study authors said: “The findings of VERIFY support and emphasise the importance of achieving and maintaining early glycaemic control.”
They added: “Early intervention with a combination therapy strategy provides greater and durable long-term benefits compared with the current standard-of-care monotherapy with metformin for patients with newly diagnosed type 2 diabetes.”
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