Safety and efficacy of linagliptin in type 2 diabetes (T2D) patients (pts) with common renal and cardiovascular risk factors

Eynatten M. von; Y. Gong; A. Emser; H. Woerle

Introduction: Vascular complications are the leading cause of morbidity and mortality in T2D. Hypertension and/or microalbuminuria predict renal and cardiovascular outcome. This large pooled analysis from a global development program aimed to evaluate the safety and efficacy of linagliptin in this particularly high-risk population.

Methods: Data of 1982 pts from 3 randomized, double-blind, placebo(PBO)-controlled phase 3 trials were analyzed. Pts with microalbuminuria (urine albumin-to-creatinine ratio [UACR] 30-300 mg/g) and hypertension (systolic BP ≧140 and/or diastolic BP ≧90 mmHg; and/or taking antihypertensive drug; and/or history of hypertension) at baseline were eligible for this analysis. Pts were treated with linagliptin 5 mg qd or PBO as monotherapy (18 wks), add-on to metformin (MET) or MET+sulphonylurea (SU) (24 wks). Efficacy endpoints were change from baseline in HbA1c and fasting plasma glucose (FPG) after 18 or 24 wks. Descriptive analysis for safety was performed, including adverse events (AE), serious AE, and hypoglycaemia episodes.

Results: 340/1982 pts met screening criteria; 251 linagliptin, 89 PBO. Baseline demographics and characteristics were similar between groups (mean [SD] HbA1c, 8.3 [0.9]%; FPG, 171 [46] mg/dL; age, 59.9 [10.2] yrs; eGFR (MDRD) ≧90/60–<90/30–<60 mL/min, 53.2%/38.5%/8.2%). Linagliptin significantly lowered HbA1c and FPG vs PBO (Table). Overall, the incidence of AE and serious AE with linagliptin were similar to PBO (AE 65.7% vs 66.3%; serious AE 3.2% vs 6.7%, respectively). Hypoglycaemic event rates were increased only when linagliptin was administered with SU (linagliptin 13.5% vs PBO 2.2%). The hypoglycaemic event rate with linagliptin was <1% as monotherapy or add-on to MET.

Conclusion: In T2D pts with hypertension and microalbuminuria, linagliptin was well tolerated and achieved significant, clinically meaningful improvements in glycaemic control. Linagliptin may support long-term preventive strategies to reduce risk of cardiovascular events and declining renal function.

Table 1 Red blood cell fatty acid composition in volunteers (% of total FA)
Adjusted mean change from baseline (SE)		Linagliptin	Placebo	Linagliptine Placebo
HbA1c (%)	Wk 18†	−0.43 (0.08)	0.19 (0.10)	−0.62 (0.12)***
	Wk 24‡	−0.55 (0.09)	0.04 (0.12)	−0.59 (0.13)***
FPG (mg/dL)	Wk 18† †	−5.12 (3.33)	6.29 (4.77)	−11.41 (5.06)*
	Wk 24‡ ‡	−3.76 (4.36)	15.95 (6.15)	−19.72 (6.35)**
P<0.05, P<0.01, **P<0.0001 vs placebo †Linagliptin: n=246, placebo: n=87; ‡linagliptin: n=218, placebo, n=69. † †Linagliptin: n=212, placebo: n=63; ‡ ‡linagliptin: n=208, placebo: n=64.

Declaration of interest: I fully declare a conflict of interest. Details below:

Funding: This work was supported, however funding details unavailable.

Endocrine Abstracts

P709