An extended trial of a drug for people with type 2 diabetes has
confirmed that the oral DPP-4 inhibitor linagliptin is a safe and
effective means of lowering glucose levels for up to 102 weeks, either
on its own or in combination with other selected oral anti-diabetic
medication.
The 32-country study, published in the August issue of IJCP, the
International Journal of Clinical Practice, followed 2,121 individuals
who had taken part in four previous 24-week randomised, double-blind,
placebo controlled trials, in order to monitor them for a further 78
weeks.
Those subjects who had previously received linagliptin (1,532) continued
to do so and those who had received the placebo during the earlier
trials (589) were also given the drug during the 78-week trial extension.
The participants who took part in the extended trial came from 231 sites
in 32 countries: Argentina, Austria, Belgium, Canada, China, Croatia,
the Czech Republic, Finland, Germany, Greece, Hungary, India, Israel,
Italy, Japan, Korea, Malaysia, Mexico, the Netherlands, New Zealand, the
Philippines, Poland, Romania, Russia, Slovakia, Spain, Sweden, Taiwan,
Thailand, Ukraine, the United Kingdom and the United States.
“Initial 24-week trials showed that linagliptin, either on its own or
with other glucose-lowering agents, was effective in improving glycaemic
control without weight gain or an independent increased risk of
hypoglycaemia (reduced blood sugar levels)” says co-author David R
Owens, Professor Emeritus, Centre for Endocrinology and Diabetes
Sciences at Cardiff University, Wales, UK.
“Linagliptin works by blocking the action of DPP-4, an enzyme that
destroys the hormone GLP-1, which helps the body produce more insulin
when it is needed.”
Linagliptin was administered orally once a day in all cases, either on
its own, or in combination with metformin or metformin plus a
sulphonylurea or pioglitazone.
Key findings of the extended study included:
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The study participants had an average age of 57.5 years, 75% were
younger than 65 years, 51.8% were male and 52.5% had been diagnosed
more than five years ago.
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The majority had a body mass index of less than 30 kg/m2 (62.4%), a
normal or mildly impaired kidney function (95.6%) and glycated
hemoglobin levels of less than 8% (71.2%). The mean baseline glycated
haemoglobin and fasting plasma glucose levels were significantly lower
in those subjects who had received linagliptin rather than the placebo
in the previous 24-week trials.
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1,880 people (88.6%) completed the trial. The main reasons for
discontinuing were adverse side effects (3.7%), refusal to continue
medication (2.6%) and lack of therapeutic effect (1.1%).
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1,718 subjects (81%) reported at least one adverse episodes during the
extension phase. The highest incidence were in people receiving the
combination of linagliptin plus metformin and a sulphonylurea (84.2%),
followed by those receiving linagliptin plus metformin (81.6%). When
linagliptin was taken on its own, the adverse side effects rate was
lower at 78.8%, similar to those on linagliptin plus pioglitazone
(76%).
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Most adverse side effects were mild or moderate and the incidence of
severe adverse side effects was low at 3.8%, with 3.4% discontinuing
the drug as a result. Overall, 14.3% of participants experienced
drug-related adverse incidents.
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The investigators determined that 13.9% of participants experienced
hyploglycaemic (low blood sugar) events and that about half of these
(6.9%) were drug-related.
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The highest level of drug-related hypoglycaemic events occurred in
persons receiving metformin with a sulophonylurea (11%), with much
lower rates for those receiving linagliptin plus metformin (2.1%),
lingaliptin on its own (0.5%) and lingaliptin plus pioglitazone (0.2%).
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Serious adverse events were reported in 9.9% of the trial subjects,
with eight deaths reported during the study period. However, these
were not related to the drug.
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Long-term lingagliptin use was not associated with a clinically
relevant change in body weight, with individuals previously on the
drug losing an average of 0.03kg and those previously on the placebo
gaining an average of 0.47 kg.
“This is the largest data set of long-term clinical evidence for
linagliptin to date” concludes Professor Owens.
“Findings from the 78-week open-label extension involving 2,121 people
with type 2 diabetes demonstrate sustained glycaemic control for up to
102 weeks treatment duration.
“They also provide evidence that supports the efficacy and tolerability
profile seen in previously reported 24-week studies. Therefore this
extension study shows that linagliptin is an effective and well
tolerated therapy for the long-term management of type 2 diabetes.”
The paper is free online at: http://onlinelibrary.wiley.com/doi/10.1111/j.1742-1241.2012.02975.x/full
