Introduction

Treatment with fixed-dose combination (FDC) of medications having complementary mechanisms of action is known to improve medication adherence by reducing pill burden. Moreover, amongst patients with type-2 diabetes mellitus (T2DM), an FDC is known to improve the glycemic control. The safety and efficacy of an FDC of a sodium-glucose co-transporter (SGLT)- 2 inhibitor empagliflozin and a dipeptidyl peptidase (DPP)-4 inhibitor linagliptin has been demonstrated in T2DM patients.

Aim

To determine the safety and efficacy of the FDC of empagliflozin/linagliptin in T2DM patients in Japan.

Patient Profile

• Patients with T2DM who were treated with the FDC empagliflozin/linagliptin.
• The effectiveness analysis set comprised of those subjects from the safety analysis with estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.73 m².

Methods

Study Design

• A one-year post-marketing surveillance (PMS) study conducted across 159 centres in Japan.

Treatment Strategy

• The study population received either empagliflozin 10 mg/linagliptin 5 mg or empagliflozin 25 mg/linagliptin 5 mg tablets.

Outcomes

Safety Outcomes

• The incidence of adverse drug reactions (ADRs), and the incidence of prespecified adverse events (AEs) and serious AEs (SAEs).

Prespecified Efficacy Outcomes

• Changes from baseline in glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG).

Results

• The total study population comprised of 1164 patients; of these, 1146 were included in the safety analysis. The effectiveness analysis comprised of 994 subjects.
• The mean age of the study population was 63.8 years, 22.08% of them were aged ≥75 years. Mean HbA1c of the study population was 7.66%, and mean FPG was 142.90 mg/dL.
• The mean treatment period with the FDC empagliflozin/linagliptin was 52.68 weeks.
• The incidence of at least one ADR was 2.79% (n=32). Overall, 2.45% of patients aged <65 years (14/572), 4.98% of those aged ≥65 to <75 years (16/321), and 0.79% of those aged ≥75 years (2/253) experienced ≥1 ADR.
• Only one case of serious ADR was reported (i.e. 0.09% of all patients) in a 73-year-old man.
• The important ADRs identified during the study included urinary tract infection (0.61%), hypoglycemia (0.17%), ketoacidosis (0), genital infection (0.09%), and volume depletion (0.09%).
• Overall, the mean body weight reduced by -1.08 kg, from baseline to end of the study period change.
• The FDC empagliflozin/linagliptin reduced mean HbA1c by −0.39% and FPG by −7.90 mg/dl from baseline to last observation. Results were similar across the age categories under consideration (Table 1).

Table 1: Change in HbA1c & FBG during the study period

Conclusions

• Empagliflozin/linagliptin FDC was effective and generally well tolerated in Japanese patients with T2DM. The safety and efficacy outcomes of the FDC were consistent across age groups; <65, ≥65 to <75, and ≥75 years.
• No new safety concerns were identified during this post-marketing surveillance.

Expert Opin Drug Saf. 2023 Feb;22(2):153-163.