Linagliptin as add‐on to empagliflozin and metformin in patients with type 2 diabetes: Two 24‐week randomized, double‐blind, double‐dummy, parallel‐group trials

Abstract

Linagliptin as add-on to empagliflozin and metformin for 24 weeks improved glycaemic control vs placebo, and was well tolerated.

DPP‐4/SGLT2 inhibitor combined therapy for type 2 diabetes

“…11,12 Adding an SGLT2 inhibitor to metformin/DPP-4 inhibitor is also associated with a small reduction in blood pressure of about 1.0-2.5mmHg above the effect of placebo for systolic and diastolic pressures 11,12 but there is little impact when a DPP-4 inhibitor is the third drug added. 10,13 These trials did not report the effects on glycaemic control according to baseline HbA 1C but, according to regulatory reviews, adding empagliflozin to metformin/linagliptin was more effective in patients with higher pretreatment HbA 1C 14 whereas adding saxagliptin to metformin/dapagliflozin had limited effect in patients with high HbA 1C (defined as ≥75mmol/mol, ≥9%). 15 However, patients in the linagliptin/empagliflozin study had better baseline glycaemic control than those in the saxagliptin/ dapagliflozin study, suggesting that comparison between the trials is inappropriate.…”

“…Adding a DPP-4 inhibitor to metformin/SGLT2 inhibitor was not associated with an increase in the frequency of adverse events in phase 3 trials. 10,13 Urinary tract infection was slightly but consistently more frequently reported with add-on linagliptin (8-10% vs 5-6% with placebo) or add-on saxagliptin (5% vs 4%); hypoglycaemia was rare.…”

Sodium-glucose cotransporter 2 inhibitors combined with dipeptidyl peptidase-4 inhibitors in the management of type 2 diabetes: a review of current clinical evidence and rationale

“…Clinical data from RCTs using DPP-4 inhibitor plus SGLT2 inhibitor combination therapy in patients with T2DM by background therapy and treatment sequence are shown in Table 568–75 and are discussed below. Studies for inclusion were selected on the basis of being Phase III RCTs of at least 24 weeks’ duration; post hoc analyses were excluded.…”

“…Results from two additional 24-week RCTs to investigate combination therapy with empagliflozin plus linagliptin were published recently; empagliflozin (10 or 25 mg/day) and linagliptin (5 mg/day) combinations were administered as single-pill formulations in both studies 74,75. One study (N=333) evaluated empagliflozin vs placebo as add-on therapy to linagliptin and metformin,74 and the second study (N=709) evaluated linagliptin vs placebo as add-on therapy to empagliflozin and metformin 75.…”

“…One study (N=333) evaluated empagliflozin vs placebo as add-on therapy to linagliptin and metformin,74 and the second study (N=709) evaluated linagliptin vs placebo as add-on therapy to empagliflozin and metformin 75. Empagliflozin/linagliptin combination therapy (plus metformin) produced greater reductions in HbA 1c and FPG from baseline than that observed with either linagliptin plus placebo (plus metformin) or empagliflozin plus placebo (plus metformin) 74,75. Adverse events were more common in the placebo groups in both studies, and the incidence of confirmed hypoglycemic adverse events was low in both studies and across all treatment groups (0%–2.7%) 74,75.…”