A study confirms that the oral DPP-4 inhibitor linagliptin is a safe and effective means of lowering glucose levels for up to 102 weeks. The drug can lower glucose levels either on its own or in combination with other selected oral anti-diabetic medication. The study of the drug for people with type 2 diabetes was conducted in 32 countries including India.
The study 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)," said 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," he explained.
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.
The study found that 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.
About 1,880 people (88.6percent) completed the trial. The main reasons for discontinuing were adverse side effects (3.7percent), refusal to continue medication (2.6percent) and lack of therapeutic effect (1.1percent).
1,718 subjects (81percent) 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 (84.2percent), followed by those receiving linagliptin plus metformin (81.6 percent). When linagliptin was taken on its own, the adverse side effects rate was lower at 78.8 percent, similar to those on linagliptin plus pioglitazone (76 percent).
Most adverse side effects were mild or moderate and the incidence of severe adverse side effects was low at 3.8 percent, with 3.4 percent discontinuing the drug as a result. Overall, 14.3 percent of participants experienced drug-related adverse incidents.
The investigators determined that 13.9percent of participants experienced hyploglycaemic (low blood sugar) events and that about half of these (6.9percent) were drug-related.
The highest level of drug-related hypoglycaemic events occurred in persons receiving metformin with a sulophonylurea (11percent), with much lower rates for those receiving linagliptin plus metformin (2.1percent), lingaliptin on its own (0.5percent) and lingaliptin plus pioglitazone (0.2percent).
Serious adverse events were reported in 9.9percent of the trial subjects, with eight deaths reported during the study period. However, these were not related to the drug.
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," concluded 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 study has been published in the August issue of IJCP, the International Journal of Clinical Practice.