Initial combination of linagliptin and metformin in patients with type 2 diabetes: efficacy and safety in a randomised, double‐blind 1‐year extension study

Abstract

ObjectiveTo determine the efficacy and safety of linagliptin in initial combination with metformin in patients with type 2 diabetes.MethodsThis 1-year randomised, double-blind study was an extension of a 6-month randomised controlled trial, in which adults with type 2 diabetes received one of six treatment regimens (linagliptin 2.5 mg plus metformin 500 mg bid, linagliptin 2.5 mg plus metformin mg 1000 bid, metformin 1000 mg bid, metformin 500 mg bid, linagliptin 5 mg qd or placebo). In the extension, patients in the first three treatment groups continued their regimen (non-switched group, n = 333) while the metformin 500 mg bid, linagliptin 5 mg qd and placebo groups were re-randomised to one of the three continuing regimens (switched group, n = 233).ResultsAll three non-switched groups maintained reductions in glycosylated haemoglobin (HbA1c; mean ± standard deviation reductions across the 1.5-year period: linagliptin 2.5 plus metformin 1000 bid, –1.63 ± 1.05%; linagliptin 2.5 plus metformin 500 bid, –1.32 ± 1.06%; metformin 1000 bid, –1.25 ± 0.91%) while the switched groups showed additional HbA1c reductions. During the extension, there were no clinically meaningful changes in body weight in any group. Adverse event rates were similar between groups, with most events being mild or moderate, and the incidence of investigator-defined hypoglycaemia was low, with no severe events.DiscussionInitial combination of linagliptin and metformin was well tolerated over the 1-year extension period, with low risk of hypoglycaemia, and improved glycaemic control vs. metformin alone.ConclusionThe initial combination of linagliptin and metformin appears to provide a useful treatment option in patients whose blood glucose levels are increased to an extent that metformin monotherapy may not achieve treatment targets.

Efficacy and safety of linagliptin in Hispanic/Latino patients with type 2 diabetes mellitus: a pooled analysis from six randomized placebo-controlled phase 3 trials

“… 26 Further evidence of the efficacy of this combination was provided by a 52-week study demonstrating that initial combination therapy with linagliptin and metformin was superior to metformin monotherapy for reducing HbA1c levels in patients with poor glycemic control, with the additional benefits of no weight gain and a low risk of hypoglycemia. 27 …”

Combination of Linagliptin and Metformin for the Treatment of Patients with Type 2 Diabetes

“…Notably, only 14 of 31 patients with baseline HbA 1c levels ≥9% remained in the metformin monotherapy group at the end of the extension trial ( Table 2 ). 9 …”

Combination Glucose-Lowering Therapy Plans in T2DM: Case-Based Considerations

“…Not surprisingly, results from several studies have shown that initial combination therapy with metformin and a DPP-4 inhibitor provides greater improvement in glycemic control than monotherapy with either agent [14,[18][19][20]. For example, results from a 24-week study with linagliptin plus metformin demonstrated greater placebo-corrected reductions in HbA1c with initial combination therapy than monotherapy with either component: -1.7% for linagliptin 5 mg/metformin 2000 mg, -1.3% for linagliptin 5 mg/metformin 1000 mg, -1.2% for metformin 2000 mg, -0.8% for metformin 1000 mg, and -0.6% for linagliptin 5 mg (all p \ 0.0001) [18].…”