TY - JOUR
T1 - Safety and Tolerability of Combinations of Empagliflozin and Linagliptin in Patients with Type 2 Diabetes
T2 - Pooled Data from Two Randomized Controlled Trials
AU - DeFronzo, Ralph A.
AU - Lee, Christopher
AU - Kohler, Sven
N1 - Publisher Copyright:
© 2018, The Author(s).
PY - 2018/7/1
Y1 - 2018/7/1
N2 - Introduction: Two 52-week Phase III studies evaluated the efficacy and safety of once-daily combinations of empagliflozin/linagliptin as monotherapy or add-on to metformin in patients with type 2 diabetes (T2DM). The aim of this analysis was to further assess the safety and tolerability of empagliflozin/linagliptin compared with their individual components in patients with T2DM, using pooled data from these trials. Methods: A total of 1363 patients were treated with empagliflozin 25 mg/linagliptin 5 mg (n = 273), empagliflozin 10 mg/linagliptin 5 mg (n = 272), empagliflozin 25 mg (n = 276), empagliflozin 10 mg (n = 275), or linagliptin 5 mg (n = 267). Adverse events (AEs) were assessed descriptively in patients who took ≥ 1 dose of study drug. Results: Total exposure was 251, 255, 256, 249, and 243 patient-years in the empagliflozin 25 mg/linagliptin 5 mg, empagliflozin 10 mg/linagliptin 5 mg, empagliflozin 25 mg, empagliflozin 10 mg, and linagliptin 5 mg groups, respectively. The proportion of patients with ≥ 1 AE was similar across groups (70.4–74.9%). The percentage of patients with confirmed hypoglycemic AEs (plasma glucose ≤ 70 mg/dL and/or requiring assistance) was low in all groups (1.1–2.2%); none required assistance. Events consistent with urinary tract infection were reported in similar percentages of patients in all groups (11.4–13.8%), and in a greater proportion of female than male patients. Events consistent with genital infection were reported in higher percentages of patients on empagliflozin/linagliptin or empagliflozin (4.0–6.5%) than linagliptin 5 mg (2.6%), and in a greater proportion of females than males. The risks of hypersensitivity reactions and events consistent with volume depletion were low across treatment groups. Conclusion: Empagliflozin/linagliptin as monotherapy or add-on to metformin for 52 weeks was well tolerated in patients with T2DM, with safety profiles similar to individual components, including a low risk of hypoglycemia. Funding: The Boehringer Ingelheim & Eli Lilly and Company Diabetes Alliance. Trial Registration: ClinicalTrials.gov identifiers, NCT01422876 & NCT01422876.
AB - Introduction: Two 52-week Phase III studies evaluated the efficacy and safety of once-daily combinations of empagliflozin/linagliptin as monotherapy or add-on to metformin in patients with type 2 diabetes (T2DM). The aim of this analysis was to further assess the safety and tolerability of empagliflozin/linagliptin compared with their individual components in patients with T2DM, using pooled data from these trials. Methods: A total of 1363 patients were treated with empagliflozin 25 mg/linagliptin 5 mg (n = 273), empagliflozin 10 mg/linagliptin 5 mg (n = 272), empagliflozin 25 mg (n = 276), empagliflozin 10 mg (n = 275), or linagliptin 5 mg (n = 267). Adverse events (AEs) were assessed descriptively in patients who took ≥ 1 dose of study drug. Results: Total exposure was 251, 255, 256, 249, and 243 patient-years in the empagliflozin 25 mg/linagliptin 5 mg, empagliflozin 10 mg/linagliptin 5 mg, empagliflozin 25 mg, empagliflozin 10 mg, and linagliptin 5 mg groups, respectively. The proportion of patients with ≥ 1 AE was similar across groups (70.4–74.9%). The percentage of patients with confirmed hypoglycemic AEs (plasma glucose ≤ 70 mg/dL and/or requiring assistance) was low in all groups (1.1–2.2%); none required assistance. Events consistent with urinary tract infection were reported in similar percentages of patients in all groups (11.4–13.8%), and in a greater proportion of female than male patients. Events consistent with genital infection were reported in higher percentages of patients on empagliflozin/linagliptin or empagliflozin (4.0–6.5%) than linagliptin 5 mg (2.6%), and in a greater proportion of females than males. The risks of hypersensitivity reactions and events consistent with volume depletion were low across treatment groups. Conclusion: Empagliflozin/linagliptin as monotherapy or add-on to metformin for 52 weeks was well tolerated in patients with T2DM, with safety profiles similar to individual components, including a low risk of hypoglycemia. Funding: The Boehringer Ingelheim & Eli Lilly and Company Diabetes Alliance. Trial Registration: ClinicalTrials.gov identifiers, NCT01422876 & NCT01422876.
KW - Adverse drug event
KW - Dipeptidyl peptidase-4 inhibitor
KW - Drug side effects
KW - Hypoglycemia
KW - SGLT2 inhibitor
UR - http://www.scopus.com/inward/record.url?scp=85048583499&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85048583499&partnerID=8YFLogxK
U2 - 10.1007/s12325-018-0724-y
DO - 10.1007/s12325-018-0724-y
M3 - Article
C2 - 29949041
AN - SCOPUS:85048583499
SN - 0741-238X
VL - 35
SP - 1009
EP - 1022
JO - Advances in Therapy
JF - Advances in Therapy
IS - 7
ER -