New data from a Phase IV study evaluating Linagliptin ( 5 mg ) as monotherapy and in combination with Metformin ( 1500 or 2000 mg ) in treatment-naive adults with newly diagnosed ( less than 12 months ) uncontrolled type 2 diabetes ( T2D ) were presented during the 2013 World Diabetes Congress, in Melbourne, Australia.
The results showed that Linagliptin as monotherapy or in initial combination with Metformin achieved clinically significant improvements in glucose control in patients with newly diagnosed type 2 diabetes and marked hyperglycaemia.
Results also showed both treatments provided statistically significant reductions in blood glucose levels, with the combination therapy having greater glucose reduction compared to monotherapy.
The study randomised 316 adults with a mean average plasma glucose concentration ( HbA1c ) of 9.8% to receive Linagliptin 5 mg once-daily ( n=157 ) and the initial combination of Linagliptin 5 mg once-daily plus Metformin twice-daily ( uptitrated to a maximal dose of 2000 mg/die; n = 159 ) for 24 weeks.
The results showed:
Linagliptin monotherapy and Linagliptin plus Metformin initial combination therapy demonstrated statistically significant reductions in HbA1c of 2.0% and 2.8%, respectively.;
HbA1c reduction with the initial combination of Linagliptin plus Metformin was statistically superior to Linagliptin alone;
A proportion of patients achieved a target HbA1c of less than 7% at week 24 with Linagliptin plus Metformin and Linagliptin monotherapy ( 61% and 39%, respectively );
Both treatments were well tolerated overall with few drug-related or serious adverse events; hypoglycaemia occurred in 3.2% and 1.9% with Linagliptin monotherapy and Linagliptin plus Metformin initial combination therapy, respectively; body weight was stable with Linagliptin and decreased in the combination arm ( -1.3 kg between group difference ).
The FDA ( Food and Drug Administration ), EMA ( European Medicines Agency ) and several other regulatory authorities worldwide have approved Linagliptin ( Europe as Trajenta and in the U.S. as Tradjenta ) for the treatment of adults with type 2 diabetes as monotherapy or in combination with Metformin ( Jentadueto ), Metformin plus sulphonylurea, and as add-on therapy to Insulin.
With Linagliptin, except as fixed dose combination with Metformin, no dose adjustment is required regardless of renal or hepatic function and hence, it can be used at one single dose in a broad range of patients.
In this international double-blind clinical trial, 316 treatment naïve subjects with recently diagnosed ( less than 12 months ) and uncontrolled diabetes mellitus ( baseline HbA1c 8.5 to 12.0% ) were randomised to receive Linagliptin 5 mg once daily ( n=157 ) or the initial combination of Linagliptin 5 mg once-daily plus Metformin twice-daily ( initial dose of 1000 mg/d uptitrated in the first six weeks; maximal dose 2000 mg/d; n=159 ) for 24 weeks.
The primary endpoint was the difference in change from baseline HbA1c between groups in the per-protocol cohort of subjects completing the trial exclusively on study drug ( Linagliptin, n=113; Linagliptin plus Metformin, n=132 ). The study did not include a placebo-controlled arm.
Linagliptin should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis ( increased ketones in the blood or urine ).
Source: Boehringer-Ingelheim, 2013