The oral DPP-4 inhibitor linagliptin has been declared safe and effective in reducing glucose levels for up to 102 weeks, either as a stand-alone treatment or in combination with other selected oral anti-diabetic drugs, according to extended trials of individuals with type 2 diabetes in 32 different countries.

The study, featured in the August edition of IJCP, was conducted to monitor 2,121 previous participants who took part in 4 previous 24-week randomized, double-blind, placebo controlled trials for an additional period of 78 more weeks.

1,532 of participants who previously received linagliptin continued their therapy, whilst 589 participants who were in the placebo group in previous trials also received linagliptin during the 78-week trial extension.

The trial was conducted at 231 sites in 32 countries, including: 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 UK and the U.S.

The study’s co-author, David R Owens, Professor Emeritus, from Cardiff University’s Centre for Endocrinology and Diabetes Sciences in Wales in the UK declared:

“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 hypoglycemia (reduced blood sugar levels). 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.”

All participants were orally given Linagliptin once a day, either on its own or in combination with metformin or metformin plus a sulphonylurea or pioglitazone.

The average age of study participants was 57.5 years, whilst 75% were younger than 65 years, 51.8% were male and in 52.5% the diagnosis occurred longer than five years ago. Most participants (62.4%) had a BMI of less than 30 kg/m2, whilst 95.6% had a normal or mildly impaired kidney function and 71.2% had glycated hemoglobin levels of less than 8%.

The researchers noted that the average baseline glycated hemoglobin and fasting plasma glucose levels were substantially lower in the linagliptin group compared with those who received placebo in the previous 24-week trials. Overall, 1,880 people (88.6%) completed the trial, whilst 3.7% discontinued treatment because of adverse side effects.

Overall, 14.3% of participants experienced drug-related adverse incidents. 2.6% refused continuing the medication and 1.1% discontinued due to lack of therapeutic effect. During the extension phase of the trial, 1,718 subjects (81%) reported at least one adverse episodes. The highest rate of adverse effects (84.2%) being noted in the linagliptin plus metformin and a sulphonylurea group, followed by 81.6% in the linagliptin plus metformin group.

In those who took linagliptin on its own, the rate of adverse side effects rate was lower, i.e. 78.8%, which was comparable to those in the linagliptin plus pioglitazone group (76%). The majority of adverse side effects were mild or moderate. Only 3.8% of subjects experienced severe adverse side effects, of which 3.4% discontinued treatment.

The researchers noted that 13.9% of participants experienced hypoglycemic (low blood sugar) events of which around half (6.9%) were drug-related. The highest level of drug-related hypoglycemic events occurred in the metformin with a sulophonylurea group (11%), with significantly reduced rates being observed in those in the linagliptin plus metformin (2.1%) group, whilst those in the linagliptin alone group had 0.5% of drug-related hypoglycemic events and those in the linagliptin plus pioglitazone group 0.2%. 9.9% of the participants experienced serious adverse events and 8 people died during the study period although these deaths occurred independent of the drug.

The researchers noted no link between long-term linagliptin use to clinically relevant changes in body weight. Individuals who previously took linagliptin lost an average of 0.03kg with those previously taking placebo gaining an average of 0.47 kg.

Professor Owens concludes:

“This is the largest data set of long-term clinical evidence for linagliptin to date. Findings from the 78-week open-label extension involving 2,121 people with type 2 diabetes demonstrate sustained glycemic 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.”

Written by Petra Rattue