Evidence mapPaperPMID 29949041Full record

Trial reportAdvances in therapy2018

Safety and Tolerability of Combinations of Empagliflozin and Linagliptin in Patients with Type 2 Diabetes: Pooled Data from Two Randomized Controlled Trials.

Ralph A DeFronzo, Christopher Lee, Sven Kohler

Registry-linked trialAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Advances in therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01422876 (A Phase III Randomized, Double-blind, Parallel Group Study to Evaluate the Efficacy and Safety of Once Daily Oral Administration of BI 10773 25 mg/Linagliptin 5 mg and BI 10773 10 mg/Linagliptin 5 mg Fixed Dose Combination Tablets Compared With the Individual Components), which is not on this map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01422876 phase3completednot on this map

A Phase III Randomized, Double-blind, Parallel Group Study to Evaluate the Efficacy and Safety of Once Daily Oral Administration of BI 10773 25 mg/Linagliptin 5 mg and BI 10773 10 mg/Linagliptin 5 mg Fixed Dose Combination Tablets Compared With the Individual Components (BI 10773 25 mg, BI 10773 10 mg, and Linagliptin 5 mg) for 52 Weeks in Treatment naïve and Metformin Treated Patients With Type 2 Diabetes Mellitus With Insufficient Glycaemic Control

TypeinterventionalSponsorBoehringer IngelheimRan2011 to 2013Enrolled1,405ConditionsDiabetes Mellitus, Type 2Armshigh dose FDC, BI 10773 high dose, high dose FDC placebo, low dose FDC placebo, high dose BI 10773 placebo
3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Trial
  2. Comparative Safety of SGLT2 Versus DPP4 Inhibitors in Patients with Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2026
    Article
  3. Review
  4. Article
  5. Article
  6. Expert Opinion: Optimum Clinical Approach to Combination-Use of SGLT2i + DPP4i in the Indian Diabetes Setting.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2022
    Article
  7. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors.

Ralph A DeFronzoUniversity of Texas Health Science Center, San Antonio, TX, USA. defronzo@uthscsa.edu.
Christopher LeeBoehringer Ingelheim International GmbH, Ingelheim, Germany.
Sven KohlerBoehringer Ingelheim International GmbH, Ingelheim, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionTwo 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.

methodsA 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.

resultsTotal 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.

conclusionEmpagliflozin/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.

fundingThe Boehringer Ingelheim & Eli Lilly and Company Diabetes Alliance.

trial registrationClinicalTrials.gov identifiers, NCT01422876 & NCT01422876.

Indexed as

Benzhydryl CompoundsGlucosidesHypoglycemiaLinagliptinDiabetes Mellitus, Type 2Dose-Response Relationship, DrugDrug MonitoringFemaleHumansHypoglycemic AgentsMaleMetforminMiddle AgedTreatment OutcomeBenzhydryl CompoundsempagliflozinGlucosidesHypoglycemic AgentsLinagliptinMetforminAdverse drug eventDipeptidyl peptidase-4 inhibitorDrug side effectsHypoglycemiaSGLT2 inhibitor

Identifiers

PMID29949041
PMCPMC11343821

What Socratic holds

Texttitle and abstract
LicenceCC BY-NC
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.