Initial Combination of Empagliflozin and Linagliptin in Subjects With Type 2 Diabetes

Abstract

OBJECTIVETo evaluate the efficacy and safety of empagliflozin/linagliptin in subjects with type 2 diabetes. RESEARCH DESIGN AND METHODSSubjects not receiving antidiabetes therapy for ‡12 weeks were randomized to empagliflozin 25 mg/linagliptin 5 mg (n = 137), empagliflozin 10 mg/linagliptin 5 mg (n = 136), empagliflozin 25 mg (n = 135), empagliflozin 10 mg (n = 134), or linagliptin 5 mg (n = 135) for 52 weeks. The primary end point was change from baseline in HbA 1c at week 24. % (27.3 [0.7] mmol/mol), respectively. Reductions in HbA 1c were significantly greater for empagliflozin 25 mg/linagliptin 5 mg compared with linagliptin 5 mg (P < 0.001) but not compared with empagliflozin 25 mg and were significantly greater for empagliflozin 10 mg/linagliptin 5 mg compared with the individual components (P < 0.001 for both). At week 24, 55.4%, 62.3%, 41.5%, 38.8%, and 32.3% of subjects with baseline HbA 1c ‡7% ( ‡53 mmol/mol) reached HbA 1c <7% with empagliflozin 25 mg/linagliptin 5 mg, empagliflozin 10 mg/linagliptin 5 mg, empagliflozin 25 mg, empagliflozin 10 mg, and linagliptin 5 mg, respectively. Efficacy was maintained at week 52. The proportion of subjects with adverse events (AEs) over 52 weeks was similar across groups (68.9-81.5%), with no confirmed hypoglycemic AEs. RESULTS Mean CONCLUSIONSReductions from baseline in HbA 1c with empagliflozin/linagliptin were significantly different versus linagliptin and empagliflozin 10 mg but not versus empagliflozin 25 mg. Empagliflozin/linagliptin was well tolerated.Empagliflozin is a potent and selective sodium-glucose cotransporter 2 (SGLT2) inhibitor (1) approved for the treatment of type 2 diabetes. Empagliflozin reduces renal glucose reabsorption, thereby increasing urinary glucose excretion, leading to a reduction in plasma glucose levels in subjects with type 2 diabetes in an insulinindependent manner (2). In a phase 3 trial in subjects with type 2 diabetes,

DPP-4 inhibitor plus SGLT-2 inhibitor as combination therapy for type 2 diabetes: from rationale to clinical aspects

“…Pharmacokinetic interactions: [25,33] Clinical trials: [27,28,29,35,36] Article highlights box -Type 2 diabetes (T2D) often requires the combination of several medications with complementary actions to reach glucose control targets while limiting side effects -The combination of a dipeptidyl peptidase-4 inhibitor (DPP-4i) and a sodium-glucose cotransporter type 2 inhibitor (SGLT2i) is an attractive approach for the management of T2D.…”

Empagliflozin/linagliptin single‐tablet combination: first‐in‐class treatment option

“…Relative to L5 alone, E25/L5 and E10/L5 achieved significant adjusted mean differences in HbA1c [−0.66% (−0.90, −0.43) and −0.71% (−0.94, −0.48), respectively; both p < 0.001]. Similarly, significant mean differences in HbA1c were observed with E10/L5 vs. E10, but not with E25/L5 vs. E25 13. Mean differences in body weight and FPG at 52 weeks with the STCs were significant vs. L5 alone, but not vs. the respective empagliflozin monotherapy components.…”

“…Among treatment‐naïve patients, mean differences in total cholesterol and high‐density cholesterol (HDL) were significant between E25/L5 STC and L5 mono‐treatments, but not for any other comparisons (Table 5) 13. No significant between‐group differences were noted in change in low‐density cholesterol (LDL) and triglycerides.…”

“…In the empagliflozin/linagliptin STC study in drug‐naïve patients, rates of overall AEs and drug‐related AEs were similar across all groups (Table 4) 13. No patients in the STC groups experienced confirmed hypoglycaemic events, and rates of such events were low in the mono‐treatment groups.…”

“…At 24 weeks, adjusted mean (SE) reductions from baseline were −1.08% (0.06) with E25/L5 [mean (SD) baseline, 7.99% (0.95)] and −1.24% (0.06) with E10/L5 [mean (SD) baseline, 8.04% (0.96)]. Both STCs significantly reduced mean HbA1c, fasting plasma glucose (FPG) and body weight relative to L5 alone (Table 2) 13. Compared with E10 mono‐treatment, E10/L5 STC showed a significant adjusted mean difference in HbA1c, but not in FPG or body weight (Table 2).…”