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Objective: This placebo-controlled study assessed long-term efficacy and safety of the dipeptidyl peptidase-4 inhibitor linagliptin in patients with type 2 diabetes and severe renal impairment (RI).Research Design and Methods: In this 1-year, double-blind study, 133 patients with type 2 diabetes (HbA(1c) 7.0-10.0%) and severe RI (estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m(2)) at screening were randomized to linagliptin 5 mg (n = 68) or placebo (n = 65) once daily, added to existing background therapy. The primary efficacy end point was HbA(1c) change from baseline to week 12. Efficacy and safety end points were assessed after 1 year.Results: At week 12, adjusted mean HbA(1c) decreased by -0.76% with linagliptin and -0.15% with placebo (treatment difference, -0.60%; 95% CI -0.89 to -0.31; P < 0.0001). HbA(1c) improvements were sustained with linagliptin (-0.71%) over placebo (0.01%) at 1 year (treatment difference -0.72%, -1.03 to -0.41; P < 0.0001). Mean insulin doses decreased by -6.2 units with linagliptin and -0.3 units with placebo. Overall adverse event incidence was similar over 1 year (94.1 vs. 92.3%). Incidence of severe hypoglycemia with linagliptin and placebo was comparably low (three patients per group). Linagliptin and placebo had little effect on renal function (median change in eGFR, -0.8 vs. -2.2 mL/min/1.73 m(2)), and no drug-related renal failure occurred.Conclusions: In patients with type 2 diabetes and severe RI, linagliptin provided clinically meaningful improvements in glycemic control with very low risk of severe hypoglycemia, stable body weight, and no cases of drug-related renal failure. The potential for linagliptin to spare insulin and provide long-term renal safety warrants further investigations. [ABSTRACT FROM AUTHOR]

Abstract Objective: Glycaemic control in patients with type 2 diabetes (T2DM) is often not achieved or not sustained using monotherapy such as metformin, necessitating the addition of other antihyperglycaemic agents. Linagliptin, a dipeptidyl peptidase-4 inhibitor, is licensed for 5 mg once-daily dosing. As metformin is administered twice daily, a fixed-dose combination of these compounds would require twice-daily administration of linagliptin. This study evaluated whether 2.5 mg twice-daily dosing of linagliptin has comparable efficacy and safety to 5 mg once-daily dosing when given in addition to metformin twice daily in patients with inadequate glycaemic control. Methods: A total of 491 T2DM patients with glycated haemoglobin (HbA1c) 7.0-10.0% were randomised (5:5:1) to double-blind treatment with linagliptin 2.5 mg twice daily, 5 mg once daily or placebo, respectively, in addition to continuing metformin twice daily (>=1500 mg/day or maximally tolerated dose). The primary endpoint was change from baseline in HbA1c after 12 weeks. ClinicalTrials.gov, NCT01012037. Results: Mean baseline HbA1c for all patients was 7.97%. After 12 weeks, linagliptin 2.5 mg twice daily and 5 mg once daily both significantly reduced HbA1c (placebo-adjusted changes from baseline -0.74% (95% CI -0.97, -0.52) and -0.80% (95% CI -1.02, -0.58), respectively, both p < 0.0001). The treatment difference (twice daily - once daily) between the linagliptin regimens was 0.06 (95% CI -0.07, 0.19), the upper bound of which was less than the predefined noninferiority margin (0.35%). The overall incidence of adverse events with linagliptin 2.5 mg twice daily, 5 mg once daily and placebo was 43.0%, 34.8%, and 38.6% respectively. Hypoglycaemia was rare (3.1% with linagliptin 2.5 mg twice daily, 0.9% with 5 mg once daily, 2.3% with placebo) with no severe episodes. Study limitations include duration, patient population (mainly white) and absence of postprandial glucose data. Conclusions: Linagliptin 2.5 mg twice daily had non-inferior HbA1c-lowering effects after 12 weeks compared to 5 mg once daily, with comparable safety and tolerability, in T2DM patients inadequately controlled with metformin. [ABSTRACT FROM AUTHOR]

OBJECTIVE: HbA1c values reflect overall glycemic exposure over the past 2-3 months and are determined by both fasting (FPG) and postprandial plasma glucose (PPG) levels. Cross-sectional studies suggest that attainment of HbA1c goals requires specific targeting of postprandial hyperglycemia. RESEARCH DESIGN AND METHODS: We undertook a prospective intervention trial to assess the relative contribution of controlling FPG and PPG for achieving recommended HbA1c goals. One hundred and sixty-four patients (90 male and 74 female) with unsatisfactory glycemic control (HbA1c >/=7.5%) were enrolled in an individualized forced titration intensified treatment program. RESULTS: After 3 months HbA1c levels decreased from 8.7+/-0.1 to 6.5+/-0.1% (p<0.001); FPG decreased from 174+/-4 to 117+/-2mg/dl (p<0.001); PPG decreased from 224+/-4 to 159+/-3mg/dl (p<0.001) and daylong hyperglycemia (average of premeal, postprandial and bedtime plasma glucose excluding FPG) decreased from 199+/-4 to 141+/-2mg/dl (p<0.0001). Patients' weight remained unchanged (84.0+/-1.4kg versus 82.9+/-1.5kg, p=0.36). No severe hypoglycemia occurred. Only 64% of patients achieving FPG targets of <100mg/dl achieved an HbA1c target of <7% whereas 94% of patients achieving the postprandial target of <140mg/dl did. Decreases in PPG accounted for nearly twice as much for the decreases in HbA1c as did decreases in FPG. PPG accounted approximately 80% of HbA1c when HbA1c was <6.2% and only about 40% when HbA1c was above 9.0%. CONCLUSIONS: Control of fasting hyperglycemia is necessary but usually insufficient for achieving HbA1c goals <7%. Control of postprandial hyperglycemia is essential for achieving recommended HbA1c goals. [ABSTRACT FROM AUTHOR]