M. von Eynatten

Linagliptin Lowers Albuminuria on Top of Recommended Standard Treatment in Patients With Type 2 Diabetes and Renal Dysfunction

OBJECTIVE Preclinical data suggest that linagliptin, a dipeptidyl peptidase-4 inhibitor, may lower urinary albumin excretion. The ability of linagliptin to lower albuminuria on top of renin-angiotensin-aldosterone system (RAAS) inhibition in humans was analyzed by pooling data from four similarly designed, 24-week, randomized, double-blind, placebo-controlled, phase III trials. RESEARCH DESIGN AND METHODS A pooled analysis of four completed studies identified 217 subjects with type 2 diabetes and prevalent albuminuria (defined as a urinary albumin-to-creatinine ratio [UACR] of 30−3,000 mg/g creatinine) while receiving stable doses of RAAS inhibitors. Participants were randomized to either linagliptin 5 mg/day (n = 162) or placebo (n= 55). The primary end point was the percentage change in geometric mean UACR from baseline to week 24. RESULTS UACR at week 24 was reduced by 32% (95% CI −42 to −21; P < 0.05) with linagliptin compared with 6% (95% CI −27 to +23) with placebo, with a between-group difference of 28% (95% CI −47 to −2; P = 0.0357). The between-group difference in the change in HbA1c from baseline to week 24 was −0.61% (−6.7 mmol/mol) in favor of linagliptin (95% CI −0.88 to −0.34% [−9.6 to −3.7 mmol/mol]; P < 0.0001). The albuminuria-lowering effect of linagliptin, however, was not influenced by race or HbA1c and systolic blood pressure (SBP) values at baseline or after treatment. CONCLUSIONS Linagliptin administered in addition to stable RAAS inhibitors led to a significant reduction in albuminuria in patients with type 2 diabetes and renal dysfunction. This observation was independent of changes in glucose level or SBP. Further research to prospectively investigate the renal effects of linagliptin is underway.

Initial combination of linagliptin and metformin improves glycaemic control in type 2 diabetes: a randomized, double‐blind, placebo‐controlled study

Aims: To evaluate the efficacy and safety of initial combination therapy with linagliptin plus metformin versus linagliptin or metformin monotherapy in patients with type 2 diabetes.

Linagliptin monotherapy provides superior glycaemic control versus placebo or voglibose with comparable safety in Japanese patients with type 2 diabetes: a randomized, placebo and active comparator-controlled, double-blind study

Aims: To evaluate the efficacy and safety of linagliptin 5 and 10 mg vs. placebo and voglibose in Japanese patients with type 2 diabetes mellitus (T2DM).

Safety and tolerability of linagliptin: a pooled analysis of data from randomized controlled trials in 3572 patients with type 2 diabetes mellitus.

Aims: To assess the safety and tolerability of the dipeptidyl peptidase‐4 inhibitor linagliptin in patients with type 2 diabetes.

Linagliptin monotherapy in type 2 diabetes patients for whom metformin is inappropriate: an 18-week randomized, double-blind, placebo-controlled phase III trial with a 34-week active-controlled extension

To investigate the efficacy and safety of linagliptin, a dipeptidyl peptidase‐4 inhibitor, in type 2 diabetes mellitus (T2DM) patients for whom metformin was inappropriate.

Linagliptin treatment in subjects with type 2 diabetes with and without mild-to-moderate renal impairment

Renal disease is a frequent comorbidity of type 2 diabetes mellitus (T2DM) and an important factor complicating the choice of glucose‐lowering drugs. The aim of this analysis was to evaluate the efficacy and safety of the dipeptidyl peptidase (DPP)‐4 inhibitor linagliptin (5 mg/day) in mono, dual or triple oral glucose‐lowering regimens in subjects with T2DM and mild or moderate renal impairment (RI).

Long-term safety of linagliptin monotherapy in Japanese patients with type 2 diabetes

In a phase III study conducted among Japanese patients with type 2 diabetes mellitus (T2DM), linagliptin 5 and 10 mg showed clinically meaningful improvements in glycaemic parameters after 12 and 26 weeks compared with placebo and voglibose, respectively. This extension study assessed long‐term tolerability of linagliptin over 52 weeks.

Safety and efficacy of the dipeptidyl peptidase-4 inhibitor linagliptin in elderly patients with type 2 diabetes: a comprehensive analysis of data from 1331 individuals aged ≥ 65 years

To investigate individual patient data from a comprehensive trials programme to evaluate the safety and efficacy of the dipeptidyl peptidase‐4 (DPP‐4) inhibitor linagliptin across a range of glucose‐lowering regimens in a large elderly population with type 2 diabetes mellitus (T2DM).

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

To determine the efficacy and safety of linagliptin in initial combination with metformin in patients with type 2 diabetes.

Linagliptin is more effective than glimepiride at achieving a composite outcome of target HbA1c < 7% with no hypoglycaemia and no weight gain over 2 years

Linagliptin treatment for 104 weeks was recently reported to achieve non‐inferior glucose‐lowering effects compared with glimepiride in patients with type 2 diabetes inadequately controlled with metformin. Additional analyses from this randomised, active‐controlled, double‐blind trial have been performed in individuals completing the study on study drug without requiring rescue therapy. In this population, significantly more patients receiving linagliptin achieved HbA1c < 7% without hypoglycaemia and without body weight gain after 2 years compared with those receiving glimepiride (54% and 23%, respectively; odds ratio of 3.9, 95% confidence interval 2.6–5.7, p < 0.0001).