Trial Outcomes & Findings for Diabetes Study of Linagliptin and Empagliflozin in Children and Adolescents (DINAMO)TM (NCT NCT03429543)

Last Updated: 2024-02-23

Results Overview

Adjusted means taken from the following three models, as pre-specified in the protocol: Treatment group 1 (TG1): \[Placebo\], \[Linagliptin 5mg\] and \[Empagliflozin pooled\] Treatment group 2 (TG2): \[Placebo\] and \[Empagliflozin 10mg and 10+25mg\] Treatment group 3 (TG3): \[Placebo\] and \[Empagliflozin 10mg\] ANCOVA with continuous covariate (baseline HbA1c) and categorical covariates (treatment \& age). Effect of linagliptin and of empagliflozin was compared with placebo at an overall α of 0.05 (2-sided) using the Hochberg method to account for multiple testing. After having obtained statistically significant results for both hypotheses of the primary family of hypotheses (TG1), the secondary hypotheses were to compare the individual empagliflozin doses versus placebo (TG2 \& TG3). ANCOVA utilized a weight of zero for patients who were not in the hypothesis test of interest, a value of 2 for re-randomised patients who were in the hypothesis test of interest and a value of 1 otherwise.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

175 participants

Primary outcome timeframe

Baseline (Day 1) and week 26 of treatment.

Results posted on

2024-02-23

Participant Flow

This study was a randomised, placebo-controlled, double-blind, and parallel group trial with 3 treatment arms (placebo, 5 mg linagliptin, 10 mg empagliflozin). The main trial DINAMOᵀᴹ consisted of patients treated with metformin and/or insulin or patients who do not tolerate metformin. The ancillary trial DINAMOᵀᴹ Mono consisted of treatment-naïve patients or patients not on active treatment.

All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.

Participant milestones

Participant milestones
Measure	Placebo - DINAMOᵀᴹ & DINAMOᵀᴹ Mono Patients treated with metformin and/or insulin or patients who do not tolerate metformin or treatment-naïve patients or patients who are not on active treatment took 1 film-coated tablet of either Linagliptin or Empagliflozin matched placebo once daily, until end of treatment.	Placebo - Linagliptin 5 mg - DINAMOᵀᴹ & DINAMOᵀᴹ Mono Patients treated with metformin and/or insulin or patients who do not tolerate metformin or treatment-naïve patients or patients who are not on active treatment took 1 film-coated tablet of either Linagliptin or Empagliflozin matched placebo once daily. At week 26, patients were re-randomised to receive 5 milligram (mg) Linagliptin, taken once daily, until end of treatment.	Placebo - Empagliflozin 10 mg - DINAMOᵀᴹ & DINAMOᵀᴹ Mono Patients treated with metformin and/or insulin or patients who do not tolerate metformin or treatment-naïve patients or patients who are not on active treatment took 1 film-coated tablet of either Linagliptin or Empagliflozin matched placebo once daily. At week 26, patients were re-randomised to receive 10 milligram (mg) empagliflozin, taken once daily, until end of treatment.	Placebo - Empagliflozin 25 mg - DINAMOᵀᴹ & DINAMOᵀᴹ Mono Patients treated with metformin and/or insulin or patients who do not tolerate metformin or treatment-naïve patients or patients who are not on active treatment took 1 film-coated tablet of either Linagliptin or Empagliflozin matched placebo once daily. At week 26, patients were re-randomised to receive 25 milligram (mg) empagliflozin, taken once daily, until end of treatment.	Linagliptin 5 mg - DINAMOᵀᴹ & DINAMOᵀᴹ Mono Patients treated with metformin and/or insulin or patients who do not tolerate metformin or treatment-naïve patients or patients who are not on active treatment took 1 film-coated tablet of 5 milligram (mg) Linagliptin once daily, until end of treatment.	Empagliflozin 10 mg - DINAMOᵀᴹ & DINAMOᵀᴹ Mono Patients treated with metformin and/or insulin or patients who do not tolerate metformin or treatment-naïve patients or patients who are not on active treatment took 1 film-coated tablet of 10 milligram (mg) Empagliflozin once daily, until Week 14. Responder patients were not re-randomised at week 14 and continued 10 mg empagliflozin, taken once daily, until end of treatment. Non responder patients were re-randomised at Week 14 to receive 10 mg empagliflozin, taken once daily, until end of treatment.	Empagliflozin 10 mg - Empagliflozin 25 mg - DINAMOᵀᴹ & DINAMOᵀᴹ Mono Patients treated with metformin and/or insulin or patients who do not tolerate metformin or treatment-naïve patients or patients who are not on active treatment who started on 10 milligram (mg) empagliflozin, taken once daily, who did not respond at Week 12 and were re-randomised at week 14 to receive 25 mg empagliflozin, taken once daily, until end of treatment.
Overall Study STARTED	7	19	16	16	59	45	13
Overall Study Treated	7	19	16	16	58	45	13
Overall Study COMPLETED	0	17	15	14	47	36	12
Overall Study NOT COMPLETED	7	2	1	2	12	9	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo - DINAMOᵀᴹ & DINAMOᵀᴹ Mono Patients treated with metformin and/or insulin or patients who do not tolerate metformin or treatment-naïve patients or patients who are not on active treatment took 1 film-coated tablet of either Linagliptin or Empagliflozin matched placebo once daily, until end of treatment.	Placebo - Linagliptin 5 mg - DINAMOᵀᴹ & DINAMOᵀᴹ Mono Patients treated with metformin and/or insulin or patients who do not tolerate metformin or treatment-naïve patients or patients who are not on active treatment took 1 film-coated tablet of either Linagliptin or Empagliflozin matched placebo once daily. At week 26, patients were re-randomised to receive 5 milligram (mg) Linagliptin, taken once daily, until end of treatment.	Placebo - Empagliflozin 10 mg - DINAMOᵀᴹ & DINAMOᵀᴹ Mono Patients treated with metformin and/or insulin or patients who do not tolerate metformin or treatment-naïve patients or patients who are not on active treatment took 1 film-coated tablet of either Linagliptin or Empagliflozin matched placebo once daily. At week 26, patients were re-randomised to receive 10 milligram (mg) empagliflozin, taken once daily, until end of treatment.	Placebo - Empagliflozin 25 mg - DINAMOᵀᴹ & DINAMOᵀᴹ Mono Patients treated with metformin and/or insulin or patients who do not tolerate metformin or treatment-naïve patients or patients who are not on active treatment took 1 film-coated tablet of either Linagliptin or Empagliflozin matched placebo once daily. At week 26, patients were re-randomised to receive 25 milligram (mg) empagliflozin, taken once daily, until end of treatment.	Linagliptin 5 mg - DINAMOᵀᴹ & DINAMOᵀᴹ Mono Patients treated with metformin and/or insulin or patients who do not tolerate metformin or treatment-naïve patients or patients who are not on active treatment took 1 film-coated tablet of 5 milligram (mg) Linagliptin once daily, until end of treatment.	Empagliflozin 10 mg - DINAMOᵀᴹ & DINAMOᵀᴹ Mono Patients treated with metformin and/or insulin or patients who do not tolerate metformin or treatment-naïve patients or patients who are not on active treatment took 1 film-coated tablet of 10 milligram (mg) Empagliflozin once daily, until Week 14. Responder patients were not re-randomised at week 14 and continued 10 mg empagliflozin, taken once daily, until end of treatment. Non responder patients were re-randomised at Week 14 to receive 10 mg empagliflozin, taken once daily, until end of treatment.	Empagliflozin 10 mg - Empagliflozin 25 mg - DINAMOᵀᴹ & DINAMOᵀᴹ Mono Patients treated with metformin and/or insulin or patients who do not tolerate metformin or treatment-naïve patients or patients who are not on active treatment who started on 10 milligram (mg) empagliflozin, taken once daily, who did not respond at Week 12 and were re-randomised at week 14 to receive 25 mg empagliflozin, taken once daily, until end of treatment.
Overall Study Adverse Event	1	1	0	0	0	2	0
Overall Study Lost to Follow-up	1	0	0	0	1	0	0
Overall Study Withdrawal by Subject	5	0	1	2	6	3	1
Overall Study Other reason than listed	0	1	0	0	4	4	0
Overall Study Not treated	0	0	0	0	1	0	0

Baseline Characteristics

The treated set (TS) included all patients treated with at least 1 dose of randomised trial medication.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo - Linagliptin 5 mg - DINAMOᵀᴹ & DINAMOᵀᴹ Mono n=19 Participants Patients treated with metformin and/or insulin or patients who do not tolerate metformin or treatment-naïve patients or patients who are not on active treatment took 1 film-coated tablet of either Linagliptin or Empagliflozin matched placebo once daily. At week 26, patients were re-randomised to receive 5 milligram (mg) Linagliptin, taken once daily, until end of treatment.	Placebo - Empagliflozin 10 mg - DINAMOᵀᴹ & DINAMOᵀᴹ Mono n=16 Participants Patients treated with metformin and/or insulin or patients who do not tolerate metformin or treatment-naïve patients or patients who are not on active treatment took 1 film-coated tablet of either Linagliptin or Empagliflozin matched placebo once daily. At week 26, patients were re-randomised to receive 10 milligram (mg) empagliflozin, taken once daily, until end of treatment.	Placebo - Empagliflozin 25 mg - DINAMOᵀᴹ & DINAMOᵀᴹ Mono n=16 Participants Patients treated with metformin and/or insulin or patients who do not tolerate metformin or treatment-naïve patients or patients who are not on active treatment took 1 film-coated tablet of either Linagliptin or Empagliflozin matched placebo once daily. At week 26, patients were re-randomised to receive 25 milligram (mg) empagliflozin, taken once daily, until end of treatment.	Placebo - DINAMOᵀᴹ & DINAMOᵀᴹ Mono n=7 Participants Patients treated with metformin and/or insulin or patients who do not tolerate metformin or treatment-naïve patients or patients who are not on active treatment took 1 film-coated tablet of either Linagliptin or Empagliflozin matched placebo once daily, until end of treatment.	Linagliptin 5 mg - DINAMOᵀᴹ & DINAMOᵀᴹ Mono n=59 Participants Patients treated with metformin and/or insulin or patients who do not tolerate metformin or treatment-naïve patients or patients who are not on active treatment took 1 film-coated tablet of 5 milligram (mg) Linagliptin once daily, until end of treatment.	Empagliflozin 10 mg - DINAMOᵀᴹ & DINAMOᵀᴹ Mono n=45 Participants Patients treated with metformin and/or insulin or patients who do not tolerate metformin or treatment-naïve patients or patients who are not on active treatment took 1 film-coated tablet of 10 milligram (mg) Empagliflozin once daily, until Week 14. Responder patients were not re-randomised at week 14 and continued 10 mg empagliflozin, taken once daily, until end of treatment. Non responder patients were re-randomised at Week 14 to receive 10 mg empagliflozin, taken once daily, until end of treatment.	Empagliflozin 10 mg - Empagliflozin 25 mg - DINAMOᵀᴹ & DINAMOᵀᴹ Mono n=13 Participants Patients treated with metformin and/or insulin or patients who do not tolerate metformin or treatment-naïve patients or patients who are not on active treatment who started on 10 milligram (mg) empagliflozin, taken once daily, who did not respond at Week 12 and were re-randomised at week 14 to receive 25 mg empagliflozin, taken once daily, until end of treatment.	Total n=175 Participants Total of all reporting groups
Age, Continuous	14.3 years STANDARD_DEVIATION 1.7 • n=19 Participants	14.1 years STANDARD_DEVIATION 2.2 • n=16 Participants	14.8 years STANDARD_DEVIATION 1.8 • n=16 Participants	15.3 years STANDARD_DEVIATION 1.4 • n=7 Participants	14.4 years STANDARD_DEVIATION 2.1 • n=59 Participants	14.6 years STANDARD_DEVIATION 1.8 • n=45 Participants	13.9 years STANDARD_DEVIATION 2.2 • n=13 Participants	14.4 years STANDARD_DEVIATION 1.9 • n=175 Participants
Sex: Female, Male Female	12 Participants n=19 Participants	11 Participants n=16 Participants	8 Participants n=16 Participants	6 Participants n=7 Participants	36 Participants n=59 Participants	31 Participants n=45 Participants	8 Participants n=13 Participants	112 Participants n=175 Participants
Sex: Female, Male Male	7 Participants n=19 Participants	5 Participants n=16 Participants	8 Participants n=16 Participants	1 Participants n=7 Participants	23 Participants n=59 Participants	14 Participants n=45 Participants	5 Participants n=13 Participants	63 Participants n=175 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	10 Participants n=19 Participants	5 Participants n=16 Participants	7 Participants n=16 Participants	1 Participants n=7 Participants	24 Participants n=59 Participants	12 Participants n=45 Participants	6 Participants n=13 Participants	65 Participants n=175 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=19 Participants	11 Participants n=16 Participants	9 Participants n=16 Participants	6 Participants n=7 Participants	35 Participants n=59 Participants	33 Participants n=45 Participants	7 Participants n=13 Participants	110 Participants n=175 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=19 Participants	0 Participants n=16 Participants	0 Participants n=16 Participants	0 Participants n=7 Participants	0 Participants n=59 Participants	0 Participants n=45 Participants	0 Participants n=13 Participants	0 Participants n=175 Participants
Race/Ethnicity, Customized American Indian/Alaska Native	1 Participants n=19 Participants	0 Participants n=16 Participants	0 Participants n=16 Participants	0 Participants n=7 Participants	3 Participants n=59 Participants	4 Participants n=45 Participants	0 Participants n=13 Participants	8 Participants n=175 Participants
Race/Ethnicity, Customized Asian	1 Participants n=19 Participants	1 Participants n=16 Participants	1 Participants n=16 Participants	0 Participants n=7 Participants	5 Participants n=59 Participants	2 Participants n=45 Participants	0 Participants n=13 Participants	10 Participants n=175 Participants
Race/Ethnicity, Customized Black/African American	4 Participants n=19 Participants	3 Participants n=16 Participants	6 Participants n=16 Participants	5 Participants n=7 Participants	17 Participants n=59 Participants	20 Participants n=45 Participants	4 Participants n=13 Participants	59 Participants n=175 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	0 Participants n=19 Participants	1 Participants n=16 Participants	0 Participants n=16 Participants	0 Participants n=7 Participants	2 Participants n=59 Participants	0 Participants n=45 Participants	0 Participants n=13 Participants	3 Participants n=175 Participants
Race/Ethnicity, Customized White	13 Participants n=19 Participants	10 Participants n=16 Participants	9 Participants n=16 Participants	1 Participants n=7 Participants	28 Participants n=59 Participants	17 Participants n=45 Participants	7 Participants n=13 Participants	85 Participants n=175 Participants
Race/Ethnicity, Customized Other including mixed or missing race	0 Participants n=19 Participants	1 Participants n=16 Participants	0 Participants n=16 Participants	1 Participants n=7 Participants	4 Participants n=59 Participants	2 Participants n=45 Participants	2 Participants n=13 Participants	10 Participants n=175 Participants
HbA1c	8.01 percentage STANDARD_DEVIATION 1.42 • n=19 Participants • The treated set (TS) included all patients treated with at least 1 dose of randomised trial medication.	8.00 percentage STANDARD_DEVIATION 1.28 • n=16 Participants • The treated set (TS) included all patients treated with at least 1 dose of randomised trial medication.	8.14 percentage STANDARD_DEVIATION 1.17 • n=16 Participants • The treated set (TS) included all patients treated with at least 1 dose of randomised trial medication.	7.40 percentage STANDARD_DEVIATION 0.77 • n=7 Participants • The treated set (TS) included all patients treated with at least 1 dose of randomised trial medication.	7.98 percentage STANDARD_DEVIATION 1.09 • n=58 Participants • The treated set (TS) included all patients treated with at least 1 dose of randomised trial medication.	7.78 percentage STANDARD_DEVIATION 1.33 • n=45 Participants • The treated set (TS) included all patients treated with at least 1 dose of randomised trial medication.	8.24 percentage STANDARD_DEVIATION 1.08 • n=13 Participants • The treated set (TS) included all patients treated with at least 1 dose of randomised trial medication.	7.94 percentage STANDARD_DEVIATION 1.20 • n=174 Participants • The treated set (TS) included all patients treated with at least 1 dose of randomised trial medication.

PRIMARY outcome

Timeframe: Baseline (Day 1) and week 26 of treatment.

Population: Patients treated with at least 1 dose of trial medication who had a baseline HbA1c measurement. All data as observed were included. Any data after start of rescue medication and any on- and post-treatment values were kept. As pre-specified in the Protocol, endpoint only includes the DINAMOᵀᴹ data, subjects randomized to Empagliflozin were grouped in pre-specified treatment analysis groups (TG1, TG2, TG3) for hypotheses testing, data was not analyzed per individual arm.

Outcome measures

Outcome measures
Measure	Placebo - DINAMOᵀᴹ (TG1, TG2 & TG3) n=53 Participants Patients treated with metformin and/or insulin or patients who do not tolerate metformin took 1 film-coated tablet of either Linagliptin or Empagliflozin matched placebo once daily.	Linagliptin 5 mg - DINAMOᵀᴹ (TG1) n=52 Participants Patients treated with metformin and/or insulin or patients who do not tolerate metformin took 1 film-coated tablet of 5 milligram (mg) Linagliptin once daily.	Empagliflozin Pooled (10 mg and 25 mg) - DINAMOᵀᴹ (TG1) n=52 Participants Patients treated with metformin and/or insulin or patients who do not tolerate metformin took 1 film-coated tablet of 10 milligram (mg) Empagliflozin once daily. Patients who did not achieve an HbA1c value \<7% at Week 12, were re-randomised to receive either 10 mg or 25 mg empagliflozin in a 1:1 ratio, taken once daily, until end of treatment.	Empagliflozin 10 mg - DINAMOᵀᴹ (TG3) n=39 Participants Patients treated with metformin and/or insulin or patients who do not tolerate metformin took 1 film-coated tablet of 10 milligram (mg) Empagliflozin once daily.	Empagliflozin 10 mg - DINAMOᵀᴹ & Empagliflozin 10 - 25 mg - DINAMOᵀᴹ (TG2) n=41 Participants Patients treated with metformin and/or insulin or patients who did not tolerate metformin started on 10 mg empagliflozin, taken once daily, who did achieve an HbA1c value \<7% at Week 12 continued with 10 mg empagliflozin thereafter, until end of treatment. And Patients who started on 10 mg empagliflozin, taken once daily, who did not achieve an HbA1c value \<7% at Week 12 and were re-randomised at week 14 to receive 25 mg empagliflozin, taken once daily, until end of treatment.	Empagliflozin Pooled (10 mg and 25 mg) - DINAMOᵀᴹ Mono Treatment-naïve patients or patients who are not on active treatment took 1 film-coated tablet of 10 milligram (mg) Empagliflozin once daily. Patients who did not achieve an HbA₁c value \<7% at Week 12, were re-randomised to receive either 10 mg or 25 mg empagliflozin in a 1:1 ratio, taken once daily, until end of treatment.
Change in Glycated Haemoglobin (HbA1c) (%) From Baseline to the End of 26 Weeks - DINAMOᵀᴹ	NA Percent change TG1 Adjusted mean (95%CI): 0.68 (0.23, 1.13) TG2 Adjusted mean (95%CI): 0.66 (0.12, 1.21) TG3 Adjusted mean (95%CI): 0.68 (0.19, 1.17)	0.33 Percent change Interval -0.13 to 0.79	-0.17 Percent change Interval -0.64 to 0.31	-0.49 Percent change Interval -1.03 to 0.04	0.14 Percent change Interval -0.42 to 0.71	—

PRIMARY outcome

Timeframe: Up to 26 weeks.

Population: The modified intention-to-treat set (mITT) included all patients treated with at least 1 dose of trial medication who had a baseline HbA1c measurement. Missing values were regarded as 'treatment failures'. As pre-specified in the Protocol, endpoint only includes the ancillary study (DINAMOᵀᴹ Mono) data.

Percentage of patients with treatment failure up to or at Week 26 as a binary endpoint, defined as meeting at least one of the following criteria: * Use of rescue medication at any time up to Week 26 * Increase from baseline in HbA1c by 0.5% at Week 26 . Increase from baseline in HbA1c to above 7.0% at Week 26 in patients with baseline HbA1c \<7.0%

Outcome measures

Outcome measures
Measure	Placebo - DINAMOᵀᴹ (TG1, TG2 & TG3) n=5 Participants Patients treated with metformin and/or insulin or patients who do not tolerate metformin took 1 film-coated tablet of either Linagliptin or Empagliflozin matched placebo once daily.	Linagliptin 5 mg - DINAMOᵀᴹ (TG1) n=6 Participants Patients treated with metformin and/or insulin or patients who do not tolerate metformin took 1 film-coated tablet of 5 milligram (mg) Linagliptin once daily.	Empagliflozin Pooled (10 mg and 25 mg) - DINAMOᵀᴹ (TG1) n=6 Participants Patients treated with metformin and/or insulin or patients who do not tolerate metformin took 1 film-coated tablet of 10 milligram (mg) Empagliflozin once daily. Patients who did not achieve an HbA1c value \<7% at Week 12, were re-randomised to receive either 10 mg or 25 mg empagliflozin in a 1:1 ratio, taken once daily, until end of treatment.	Empagliflozin 10 mg - DINAMOᵀᴹ (TG3) Patients treated with metformin and/or insulin or patients who do not tolerate metformin took 1 film-coated tablet of 10 milligram (mg) Empagliflozin once daily.	Empagliflozin 10 mg - DINAMOᵀᴹ & Empagliflozin 10 - 25 mg - DINAMOᵀᴹ (TG2) Patients treated with metformin and/or insulin or patients who did not tolerate metformin started on 10 mg empagliflozin, taken once daily, who did achieve an HbA1c value \<7% at Week 12 continued with 10 mg empagliflozin thereafter, until end of treatment. And Patients who started on 10 mg empagliflozin, taken once daily, who did not achieve an HbA1c value \<7% at Week 12 and were re-randomised at week 14 to receive 25 mg empagliflozin, taken once daily, until end of treatment.	Empagliflozin Pooled (10 mg and 25 mg) - DINAMOᵀᴹ Mono Treatment-naïve patients or patients who are not on active treatment took 1 film-coated tablet of 10 milligram (mg) Empagliflozin once daily. Patients who did not achieve an HbA₁c value \<7% at Week 12, were re-randomised to receive either 10 mg or 25 mg empagliflozin in a 1:1 ratio, taken once daily, until end of treatment.
Percentage of Patients With Treatment Failure up to or at Week 26	60.0 Percentage of subjects Interval 18.9 to 92.4	50.0 Percentage of subjects Interval 15.3 to 84.7	50.0 Percentage of subjects Interval 15.3 to 84.7	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) and week 26 of treatment.

Population: The modified intention-to-treat set (mITT) included all patients treated with at least 1 dose of trial medication who had a baseline HbA1c measurement. All available data as observed were included. Any values after start of rescue medication and any on- and post-treatment values were kept. As pre-specified in the Protocol, endpoint only includes the ancillary study (DINAMOᵀᴹ Mono) data.

Change in Glycated haemoglobin (HbA1c) (%) from baseline to the end of 26 weeks. Adjusted values came from a restricted maximum likelihood (REML) approach with mixed model for repeated measures (MMRM). Analyses included fixed categorical effects of treatment, visit, and treatment-by-visit interaction, as well as the categorical covariate age at randomisation and the continuous, fixed covariates of baseline of the response variable and baseline of the response variable-by-visit interaction. The covariate visit was treated as the repeated measure with an unstructured covariance structure used to model the within-patient measurements.

Outcome measures

Outcome measures
Measure	Placebo - DINAMOᵀᴹ (TG1, TG2 & TG3) n=4 Participants Patients treated with metformin and/or insulin or patients who do not tolerate metformin took 1 film-coated tablet of either Linagliptin or Empagliflozin matched placebo once daily.	Linagliptin 5 mg - DINAMOᵀᴹ (TG1) n=5 Participants Patients treated with metformin and/or insulin or patients who do not tolerate metformin took 1 film-coated tablet of 5 milligram (mg) Linagliptin once daily.	Empagliflozin Pooled (10 mg and 25 mg) - DINAMOᵀᴹ (TG1) n=4 Participants Patients treated with metformin and/or insulin or patients who do not tolerate metformin took 1 film-coated tablet of 10 milligram (mg) Empagliflozin once daily. Patients who did not achieve an HbA1c value \<7% at Week 12, were re-randomised to receive either 10 mg or 25 mg empagliflozin in a 1:1 ratio, taken once daily, until end of treatment.	Empagliflozin 10 mg - DINAMOᵀᴹ (TG3) Patients treated with metformin and/or insulin or patients who do not tolerate metformin took 1 film-coated tablet of 10 milligram (mg) Empagliflozin once daily.	Empagliflozin 10 mg - DINAMOᵀᴹ & Empagliflozin 10 - 25 mg - DINAMOᵀᴹ (TG2) Patients treated with metformin and/or insulin or patients who did not tolerate metformin started on 10 mg empagliflozin, taken once daily, who did achieve an HbA1c value \<7% at Week 12 continued with 10 mg empagliflozin thereafter, until end of treatment. And Patients who started on 10 mg empagliflozin, taken once daily, who did not achieve an HbA1c value \<7% at Week 12 and were re-randomised at week 14 to receive 25 mg empagliflozin, taken once daily, until end of treatment.	Empagliflozin Pooled (10 mg and 25 mg) - DINAMOᵀᴹ Mono Treatment-naïve patients or patients who are not on active treatment took 1 film-coated tablet of 10 milligram (mg) Empagliflozin once daily. Patients who did not achieve an HbA₁c value \<7% at Week 12, were re-randomised to receive either 10 mg or 25 mg empagliflozin in a 1:1 ratio, taken once daily, until end of treatment.
Change in HbA1c (%) From Baseline to the End of 26 Weeks - DINAMOᵀᴹ Mono	0.15 Percent change Interval -1.45 to 1.75	-0.53 Percent change Interval -2.01 to 0.95	-0.23 Percent change Interval -1.83 to 1.37	—	—	—

SECONDARY outcome

Timeframe: Up to 395 days.

Population: The modified intention-to-treat set (mITT) included all patients treated with at least 1 dose of trial medication who had a baseline HbA1c measurement. Missing values were regarded as 'failures'. As pre-specified in the Protocol, endpoint only includes the ancillary study (DINAMOᵀᴹ Mono) data.

Time to treatment failure was analysed by Kaplan-Meier estimates up to the end of the study (Week 52). Patients in the placebo group were censored after 26 weeks unless a prior treatment failure was observed.