Trial Outcomes & Findings for Sitagliptin for Reducing Inflammation and Immune Activation (NCT NCT02513771)

NCT ID: NCT02513771

Last Updated: 2018-06-18

Results Overview

sCD14 (soluble cluster of differentiation 14) is a biomarker of gut microbial translocation and monocyte/macrophage activation. The outcome measures are changes in log10 transformed sCD14 from baseline to week 15/16 (week 15/16 - baseline) Levels measured at pre-entry and entry were averaged for baseline, levels measured at week 15 and week 16 were averaged for week 15/16.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 90 participants
• Primary outcome timeframe: Pre-entry, Week 0, Week 15, Week 16
• Results posted on: 2018-06-18

Participant Flow

First participant was enrolled on October 20, 2015. Accrual to the study closed on August 24, 2016, with 15 U.S sites registered and enrolled participants.

Participants were randomized 1:1 to Sitagliptin and Placebo arms. Randomization was stratified by screening CD4 (100-350 vs >350 cells/mm^3) and statin use.

Participant milestones

Measure	Sitagliptin Arm Sitagliptin (Januvia) 100 mg one tablet daily p.o. for 16 weeks, followed by a 4-week post-treatment follow-up.	Placebo Arm Placebo for sitagliptin one tablet daily p.o.for 16 weeks, followed by a 4-week post-treatment follow-up.
Overall Study STARTED	45	45
Overall Study COMPLETED	43	44
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Measure	Sitagliptin Arm Sitagliptin (Januvia) 100 mg one tablet daily p.o. for 16 weeks, followed by a 4-week post-treatment follow-up.	Placebo Arm Placebo for sitagliptin one tablet daily p.o.for 16 weeks, followed by a 4-week post-treatment follow-up.
Overall Study Lost to Follow-up	1	1
Overall Study Not being able to get to clinic	1	0

Baseline Characteristics

Enrolled participants with available baseline CD4 count. One participant had missing CD4 count at baseline due to missing blood samples.

Baseline characteristics by cohort

Measure	Sitagliptin Arm n=45 Participants Sitagliptin: 100 mg one tablet taken orally daily for 16 weeks, followed by a 4-week post-treatment follow-up	Placebo Arm n=45 Participants Placebo for sitagliptin: One tablet taken orally daily for 16 weeks, followed by a 4-week post-treatment follow-up.	Total n=90 Participants Total of all reporting groups
Age, Continuous	52 years n=45 Participants	50 years n=45 Participants	51 years n=90 Participants
Age, Customized 18-39 years	11 Participants n=45 Participants	6 Participants n=45 Participants	17 Participants n=90 Participants
Age, Customized 40-59 years	27 Participants n=45 Participants	32 Participants n=45 Participants	59 Participants n=90 Participants
Age, Customized >=60 years	7 Participants n=45 Participants	7 Participants n=45 Participants	14 Participants n=90 Participants
Sex: Female, Male Female	7 Participants n=45 Participants	9 Participants n=45 Participants	16 Participants n=90 Participants
Sex: Female, Male Male	38 Participants n=45 Participants	36 Participants n=45 Participants	74 Participants n=90 Participants
Race/Ethnicity, Customized Non-Hispanic White	23 Participants n=45 Participants	18 Participants n=45 Participants	41 Participants n=90 Participants
Race/Ethnicity, Customized Non-Hispanic Black	15 Participants n=45 Participants	19 Participants n=45 Participants	34 Participants n=90 Participants
Race/Ethnicity, Customized Hispanic (Regardless of Race)	7 Participants n=45 Participants	7 Participants n=45 Participants	14 Participants n=90 Participants
Race/Ethnicity, Customized more than one race	0 Participants n=45 Participants	1 Participants n=45 Participants	1 Participants n=90 Participants
Region of Enrollment United States	45 Participants n=45 Participants	45 Participants n=45 Participants	90 Participants n=90 Participants
IV drug use Never	44 Participants n=45 Participants	42 Participants n=45 Participants	86 Participants n=90 Participants
IV drug use Previously	1 Participants n=45 Participants	3 Participants n=45 Participants	4 Participants n=90 Participants
CD4 count	609 cells/mm^3 n=45 Participants • Enrolled participants with available baseline CD4 count. One participant had missing CD4 count at baseline due to missing blood samples.	551 cells/mm^3 n=44 Participants • Enrolled participants with available baseline CD4 count. One participant had missing CD4 count at baseline due to missing blood samples.	586 cells/mm^3 n=89 Participants • Enrolled participants with available baseline CD4 count. One participant had missing CD4 count at baseline due to missing blood samples.
Baseline sCD14	6.39 log10 pg/mL n=42 Participants • As-treated population limited to participants who had baseline and week 15 measurements, completed study treatment with no more than 34 cumulative days of treatment interruption, did not use prohibited medications, did not have a confirmed virologic failure at or prior to week 16 (see protocol 6.2.3).	6.38 log10 pg/mL n=42 Participants • As-treated population limited to participants who had baseline and week 15 measurements, completed study treatment with no more than 34 cumulative days of treatment interruption, did not use prohibited medications, did not have a confirmed virologic failure at or prior to week 16 (see protocol 6.2.3).	6.39 log10 pg/mL n=84 Participants • As-treated population limited to participants who had baseline and week 15 measurements, completed study treatment with no more than 34 cumulative days of treatment interruption, did not use prohibited medications, did not have a confirmed virologic failure at or prior to week 16 (see protocol 6.2.3).

PRIMARY outcome

Timeframe: Pre-entry, Week 0, Week 15, Week 16

Population: As-treated population limited to participants who had baseline and week 15/16 measurements, completed study treatment with no more than 34 cumulative days of treatment interruption, did not use prohibited medications, did not have a confirmed virologic failure at or prior to week 16 (see protocol 6.2.3).

sCD14 (soluble cluster of differentiation 14) is a biomarker of gut microbial translocation and monocyte/macrophage activation.

The outcome measures are changes in log10 transformed sCD14 from baseline to week 15/16 (week 15/16 - baseline) Levels measured at pre-entry and entry were averaged for baseline, levels measured at week 15 and week 16 were averaged for week 15/16.

Outcome measures

Measure	Sitagliptin Arm n=42 Participants Sitagliptin (Januvia) 100 mg one tablet daily p.o. for 16 weeks, followed by a 4-week post-treatment follow-up.	Placebo Arm n=42 Participants Placebo for sitagliptin one tablet daily p.o.for 16 weeks, followed by a 4-week post-treatment follow-up.
Change in sCD14 From Baseline to Week 15/16	-0.03 log10 pg/mL Interval -0.06 to 0.02	-0.03 log10 pg/mL Interval -0.08 to 0.02

SECONDARY outcome

Timeframe: Week 15, week 16, week 20

Population: As-treated population limited to participants who had baseline and week 15/16 measurements, completed study treatment with no more than 34 cumulative days of treatment interruption, did not use prohibited medications, did not have a confirmed virologic failure at or prior to week 16 (see protocol 6.2.3).

sCD14 (soluble cluster of differentiation 14) is a biomarker of gut microbial translocation and monocyte/macrophage activation.

The outcome measures are changes in log10 transformed sCD14 from week 15/16 to week 20 (week 20 - week 15/16).

Levels measured at week 15 and week 16 were averaged for week 15/16.

Outcome measures

Measure	Sitagliptin Arm n=42 Participants Sitagliptin (Januvia) 100 mg one tablet daily p.o. for 16 weeks, followed by a 4-week post-treatment follow-up.	Placebo Arm n=42 Participants Placebo for sitagliptin one tablet daily p.o.for 16 weeks, followed by a 4-week post-treatment follow-up.
Change in sCD14 From Week 15/16 to Week 20	0.04 log10 pg/mL Interval -0.02 to 0.13	0.02 log10 pg/mL Interval -0.1 to 0.11

SECONDARY outcome

Timeframe: Week 0, week 15, week 20

Population: As-treated population limited to participants who had baseline and week 15 measurements, completed study treatment with no more than 34 cumulative days of treatment interruption, did not use prohibited medications, did not have a confirmed virologic failure at or prior to week 16 (see protocol 6.2.3).

sCD163 (soluble CD 163) is a marker of macrophage activation and arterial inflammation.

Change in log10 transformed sCD163 from Week 0 to week 15 (week 15 - week 0), and from week 15 to week 20 (week 20 - week 15).

Outcome measures

Measure	Sitagliptin Arm n=42 Participants Sitagliptin (Januvia) 100 mg one tablet daily p.o. for 16 weeks, followed by a 4-week post-treatment follow-up.	Placebo Arm n=42 Participants Placebo for sitagliptin one tablet daily p.o.for 16 weeks, followed by a 4-week post-treatment follow-up.
Change in sCD163 Change from week 0 to week 15	-0.03 log10 ng/mL Interval -0.06 to 0.02	-0.02 log10 ng/mL Interval -0.09 to 0.03
Change in sCD163 Change from week 15 to week 20	0.01 log10 ng/mL Interval -0.02 to 0.05	0.00 log10 ng/mL Interval -0.06 to 0.05

SECONDARY outcome

Timeframe: Week 0, week 15, week 20

Population: As-treated population limited to participants who had baseline and week 15 measurements, completed study treatment with no more than 34 cumulative days of treatment interruption, did not use prohibited medications, did not have a confirmed virologic failure at or prior to week 16 (see protocol 6.2.3).

sCD26 (soluble cluster of differentiation 26) is an enzyme that metabolizes DPP-4 (dipeptidyl peptidase-4), an enzyme that is inhibited by sitagliptin.

Change in log10 transformed sCD26 from Week 0 to week 15 (week 15 - week 0), and from week 15 to week 20 (week 20 - week 15).

Outcome measures

Measure	Sitagliptin Arm n=42 Participants Sitagliptin (Januvia) 100 mg one tablet daily p.o. for 16 weeks, followed by a 4-week post-treatment follow-up.	Placebo Arm n=42 Participants Placebo for sitagliptin one tablet daily p.o.for 16 weeks, followed by a 4-week post-treatment follow-up.
Change in sCD26 Change from week 0 to week 15	-0.16 log10 ng/mL Interval -0.37 to 0.07	-0.16 log10 ng/mL Interval -0.52 to 0.09
Change in sCD26 Change from week 15 to week 20	0.08 log10 ng/mL Interval -0.28 to 0.24	0.04 log10 ng/mL Interval -0.16 to 0.26

SECONDARY outcome

Timeframe: Week 0, week 15, week 20

Population: As-treated population limited to participants who had baseline and week 15 measurements, completed study treatment with no more than 34 cumulative days of treatment interruption, did not use prohibited medications, did not have a confirmed virologic failure at or prior to week 16 (see protocol 6.2.3).

IL-6 (Interleukin-6) is a biomarker of systemic inflammation. Change in log10 transformed IL-6 from Week 0 to week 15 (week 15 - week 0), and from week 15 to week 20 (week 20 - week 15).

Outcome measures

Measure	Sitagliptin Arm n=42 Participants Sitagliptin (Januvia) 100 mg one tablet daily p.o. for 16 weeks, followed by a 4-week post-treatment follow-up.	Placebo Arm n=42 Participants Placebo for sitagliptin one tablet daily p.o.for 16 weeks, followed by a 4-week post-treatment follow-up.
Change in IL-6 Change from week 0 to week 15	0.00 log10 pg/mL Interval -0.12 to 0.11	0.00 log10 pg/mL Interval -0.11 to 0.14
Change in IL-6 Change from week 15 to week 20	-0.06 log10 pg/mL Interval -0.11 to 0.08	0.01 log10 pg/mL Interval -0.1 to 0.12

SECONDARY outcome

Timeframe: Week 0, week 15, week 20

Population: As-treated population limited to participants who had baseline and week 15 measurements, completed study treatment with no more than 34 cumulative days of treatment interruption, did not use prohibited medications, did not have a confirmed virologic failure at or prior to week 16 (see protocol 6.2.3).

hsCRP (high-sensitivity C-reactive protein) is a biomarker of inflammation. Change in log10 transformed hsCRP from Week 0 to week 15 (week 15 - week 0), and from week 15 to week 20 (week 20 - week 15).

Outcome measures

Measure	Sitagliptin Arm n=42 Participants Sitagliptin (Januvia) 100 mg one tablet daily p.o. for 16 weeks, followed by a 4-week post-treatment follow-up.	Placebo Arm n=42 Participants Placebo for sitagliptin one tablet daily p.o.for 16 weeks, followed by a 4-week post-treatment follow-up.
Change in hsCRP Change from week 0 to week 15	-0.08 log10 ng/mL Interval -0.18 to 0.06	-0.05 log10 ng/mL Interval -0.22 to 0.1
Change in hsCRP Change from week 15 to week 20	-0.02 log10 ng/mL Interval -0.22 to 0.09	-0.01 log10 ng/mL Interval -0.19 to 0.18

SECONDARY outcome

Timeframe: Week 0, week 15, week 20

Population: As-treated population limited to participants who had baseline and week 15 measurements, completed study treatment with no more than 34 cumulative days of treatment interruption, did not use prohibited medications, did not have a confirmed virologic failure at or prior to week 16 (see protocol 6.2.3).

sTNF-r1 (soluble tumour necrosis alpha receptor 1) is a biomarker of inflammation.

Change in log10 transformed sTNF-r1 from Week 0 to week 15 (week 15 - week 0), and from week 15 to week 20 (week 20 - week 15).

Outcome measures

Measure	Sitagliptin Arm n=42 Participants Sitagliptin (Januvia) 100 mg one tablet daily p.o. for 16 weeks, followed by a 4-week post-treatment follow-up.	Placebo Arm n=42 Participants Placebo for sitagliptin one tablet daily p.o.for 16 weeks, followed by a 4-week post-treatment follow-up.
Change in sTNF-r1 Change from week 0 to week 15	-0.01 log10 pg/mL Interval -0.05 to 0.04	-0.04 log10 pg/mL Interval -0.06 to 0.0
Change in sTNF-r1 Change from week 15 to week 20	0.00 log10 pg/mL Interval -0.03 to 0.06	-0.01 log10 pg/mL Interval -0.05 to 0.09

SECONDARY outcome

Timeframe: Week 0, week 15, week 20

Population: As-treated population limited to participants who had baseline and week 15 measurements, completed study treatment with no more than 34 cumulative days of treatment interruption, did not use prohibited medications, did not have a confirmed virologic failure at or prior to week 16 (see protocol 6.2.3).

sTNF-r2 (soluble tumour necrosis alpha receptor 2) is a biomarker of inflammation.

Change in log10 transformed sTNF-r2 from Week 0 to week 15 (week 15 - week 0), and from week 15 to week 20 (week 20 - week 15).

Outcome measures

Measure	Sitagliptin Arm n=42 Participants Sitagliptin (Januvia) 100 mg one tablet daily p.o. for 16 weeks, followed by a 4-week post-treatment follow-up.	Placebo Arm n=42 Participants Placebo for sitagliptin one tablet daily p.o.for 16 weeks, followed by a 4-week post-treatment follow-up.
Change in sTNF-r2 Change from week 0 to week 15	-0.05 log10 pg/mL Interval -0.14 to 0.13	-0.06 log10 pg/mL Interval -0.13 to 0.04
Change in sTNF-r2 Change from week 15 to week 20	0.06 log10 pg/mL Interval -0.08 to 0.2	0.05 log10 pg/mL Interval -0.07 to 0.21

SECONDARY outcome

Timeframe: Week 0, week 15, week 20

Population: As-treated population limited to participants who had baseline and week 15 measurements, completed study treatment with no more than 34 cumulative days of treatment interruption, did not use prohibited medications, did not have a confirmed virologic failure at or prior to week 16 (see protocol 6.2.3).

IP-10 (also known as CXCL10) is a biomarker implicated in cardiovascular disease.

Change in log10 transformed IP-10 from Week 0 to week 15 (week 15 - week 0), and from week 15 to week 20 (week 20 - week 15).

Outcome measures

Measure	Sitagliptin Arm n=42 Participants Sitagliptin (Januvia) 100 mg one tablet daily p.o. for 16 weeks, followed by a 4-week post-treatment follow-up.	Placebo Arm n=42 Participants Placebo for sitagliptin one tablet daily p.o.for 16 weeks, followed by a 4-week post-treatment follow-up.
Change in IP-10 Change from week 0 to week 15	-0.31 log10 pg/mL Interval -0.4 to -0.15	-0.01 log10 pg/mL Interval -0.09 to 0.12
Change in IP-10 Change from week 15 to week 20	0.23 log10 pg/mL Interval 0.17 to 0.4	0.02 log10 pg/mL Interval -0.09 to 0.08

SECONDARY outcome

Timeframe: Week 0 and week 15

Population: As-treated population limited to participants who had baseline and week 15 measurements, completed study treatment with no more than 34 cumulative days of treatment interruption, did not use prohibited medications, did not have a confirmed virologic failure at or prior to week 16 (see protocol 6.2.3).

CD4+/CD8+ T-cell ratio change from week 0 to week 15 (week 15 - week 0). Note that CD4 and CD8 were not evaluated at week 20 in this study.

Outcome measures

Measure	Sitagliptin Arm n=42 Participants Sitagliptin (Januvia) 100 mg one tablet daily p.o. for 16 weeks, followed by a 4-week post-treatment follow-up.	Placebo Arm n=42 Participants Placebo for sitagliptin one tablet daily p.o.for 16 weeks, followed by a 4-week post-treatment follow-up.
Change in CD4+/CD8+ T-cell Ratio	0.00 ratio Interval -0.11 to 0.04	0.02 ratio Interval -0.04 to 0.08

SECONDARY outcome

Timeframe: Week 0, week 15, week 20

Population: As-treated population limited to participants who had baseline and week 15/16 measurements, completed study treatment with no more than 34 cumulative days of treatment interruption, did not use prohibited medications, did not have a confirmed virologic failure at or prior to week 16 (see protocol 6.2.3).

Level of CD4+ T-cell activation was determined by measuring the percentage of cells that expressed both the activation marker CD38+ and Human leukocyte antigen (HLA)-DR+.

The endpoint is measuring the change from week 0 to week 15 (week 15 - week 0) and change from week 15 to week 20 (week 20 - week 15).

Data for cellular markers are not available as of December 2017. These data are based on immunology assays which were tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 1 month after the primary complete date. Please note that these secondary outcomes were not included in the primary analyses. There are many outcomes in this study and the immunology lab had to give priority to the assays planned to be included in the primary manuscript. Results will be entered once the data is complete and analyzed.

Outcome measures

Measure	Sitagliptin Arm n=42 Participants Sitagliptin (Januvia) 100 mg one tablet daily p.o. for 16 weeks, followed by a 4-week post-treatment follow-up.	Placebo Arm n=40 Participants Placebo for sitagliptin one tablet daily p.o.for 16 weeks, followed by a 4-week post-treatment follow-up.
Change in CD4+ T-cell Activation change from baseline to week 15	0.12 percentage of cells Interval -0.15 to 0.52	0.08 percentage of cells Interval -0.41 to 0.43
Change in CD4+ T-cell Activation change from week 15 to week 20	0.07 percentage of cells Interval -0.28 to 0.6	0.06 percentage of cells Interval -0.47 to 0.38

SECONDARY outcome

Timeframe: Week 0, week 15, week 20

Population: As-treated population limited to participants who had baseline and week 15/16 measurements, completed study treatment with no more than 34 cumulative days of treatment interruption, did not use prohibited medications, did not have a confirmed virologic failure at or prior to week 16 (see protocol 6.2.3).

Level of CD8+ T-cell activation was determined by measuring the percentage of cells that expressed both the activation marker CD38+ and Human leukocyte antigen (HLA)-DR+.

The endpoint is measuring the change from week 0 to week 15 (week 15 - week 0) and change from week 15 to week 20 (week 20 - week 15).

Data for cellular markers are not available as of December 2017. These data are based on immunology assays which were tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 1 month after the primary complete date. Please note that these secondary outcomes were not included in the primary analyses. There are many outcomes in this study and the immunology lab had to give priority to the assays planned to be included in the primary manuscript. Results will be entered once the data is complete and analyzed.

Outcome measures

Measure	Sitagliptin Arm n=42 Participants Sitagliptin (Januvia) 100 mg one tablet daily p.o. for 16 weeks, followed by a 4-week post-treatment follow-up.	Placebo Arm n=40 Participants Placebo for sitagliptin one tablet daily p.o.for 16 weeks, followed by a 4-week post-treatment follow-up.
Change in CD8+ T-cell Activation change from baseline to week 15	0.03 percentage of cells Interval -0.9 to 1.83	-0.27 percentage of cells Interval -1.11 to 1.33
Change in CD8+ T-cell Activation change from week 15 to week 20	0.11 percentage of cells Interval -0.7 to 1.9	-0.29 percentage of cells Interval -1.12 to 1.17

SECONDARY outcome

Timeframe: Week 0, week 15, week 20

Population: As-treated population limited to participants who had baseline and week 15/16 measurements, completed study treatment with no more than 34 cumulative days of treatment interruption, did not use prohibited medications, did not have a confirmed virologic failure at or prior to week 16 (see protocol 6.2.3).

CD14+/CD16- is the percentage of cells that expressed CD14 and low CD16 in total monocytes (also known as classical monocytes).

This endpoint is measuring the change from week 0 to week 15 (week 15 - week 0) and change from week 15 to week 20 (week 20 - week 15).

Data for cellular markers are not available as of November 2017. The study team prioritized completion of the soluble markers (including the primary outcome measure), which are reported herein, over the completion of the cellular markers. Results will be entered once the data is complete and analyzed.

Outcome measures

Measure	Sitagliptin Arm n=42 Participants Sitagliptin (Januvia) 100 mg one tablet daily p.o. for 16 weeks, followed by a 4-week post-treatment follow-up.	Placebo Arm n=40 Participants Placebo for sitagliptin one tablet daily p.o.for 16 weeks, followed by a 4-week post-treatment follow-up.
Change in %CD14+/CD16- (Classical Monocytes) change from baseline to week 15	-2.30 percentage of cells Interval -6.2 to 3.2	-0.80 percentage of cells Interval -4.75 to 2.75
Change in %CD14+/CD16- (Classical Monocytes) change from week 15 to week 20	0.40 percentage of cells Interval -2.4 to 6.1	-1.00 percentage of cells Interval -4.5 to 4.95

SECONDARY outcome

Timeframe: Week 0, week 15, week 20

Population: As-treated population limited to participants who had baseline and week 15/16 measurements, completed study treatment with no more than 34 cumulative days of treatment interruption, did not use prohibited medications, did not have a confirmed virologic failure at or prior to week 16 (see protocol 6.2.3).

%CD14+/CD16+ is the percentage of cells that expressed both CD14 and CD16 in total monocytes (also known as intermediate monocytes).

This endpoint is measuring the change from week 0 to week 15 (week 15 - week 0) and change from week 15 to week 20 (week 20 - week 15).

Data for cellular markers are not available as of December 2017. These data are based on immunology assays which were tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 1 month after the primary complete date. Please note that these secondary outcomes were not included in the primary analyses. There are many outcomes in this study and the immunology lab had to give priority to the assays planned to be included in the primary manuscript. Results will be entered once the data is complete and analyzed.

Outcome measures

Measure	Sitagliptin Arm n=42 Participants Sitagliptin (Januvia) 100 mg one tablet daily p.o. for 16 weeks, followed by a 4-week post-treatment follow-up.	Placebo Arm n=40 Participants Placebo for sitagliptin one tablet daily p.o.for 16 weeks, followed by a 4-week post-treatment follow-up.
Change in %CD14+/CD16+ (Intermediate Monocytes) change from baseline to week 15	0.87 percentage of cells Interval -1.32 to 3.08	-0.12 percentage of cells Interval -2.33 to 1.97
Change in %CD14+/CD16+ (Intermediate Monocytes) change from week 15 to week 20	-0.65 percentage of cells Interval -2.86 to 0.98	-0.19 percentage of cells Interval -1.5 to 1.37

SECONDARY outcome

Timeframe: Week 0, week 15, week 20

Population: As-treated population limited to participants who had baseline and week 15/16 measurements, completed study treatment with no more than 34 cumulative days of treatment interruption, did not use prohibited medications, did not have a confirmed virologic failure at or prior to week 16 (see protocol 6.2.3).

%CD14dim/CD16++ is the percentage of cells that expressed low levels of CD14dim and high levels of CD16++ in total monocytes (also known as non-classical monocytes).

This endpoint is measuring the change from week 0 to week 15 (week 15 - week 0) and change from week 15 to week 20 (week 20 - week 15).

Data for cellular markers are not available as of December 2017. These data are based on immunology assays which were tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 1 month after the primary complete date. Please note that these secondary outcomes were not included in the primary analyses. There are many outcomes in this study and the immunology lab had to give priority to the assays planned to be included in the primary manuscript. Results will be entered once the data is complete and analyzed.

Outcome measures

Measure	Sitagliptin Arm n=42 Participants Sitagliptin (Januvia) 100 mg one tablet daily p.o. for 16 weeks, followed by a 4-week post-treatment follow-up.	Placebo Arm n=40 Participants Placebo for sitagliptin one tablet daily p.o.for 16 weeks, followed by a 4-week post-treatment follow-up.
Change in %CD14dim/CD16++ (Non-classical Monocytes) change from baseline to week 15	0.31 percentage of cells Interval -1.02 to 2.05	-0.03 percentage of cells Interval -2.08 to 2.31
Change in %CD14dim/CD16++ (Non-classical Monocytes) change from week 15 to week 20	-0.37 percentage of cells Interval -1.95 to 1.76	0.12 percentage of cells Interval -1.16 to 2.89

SECONDARY outcome

Timeframe: From study entry to end of study (Week 20)

Population: All enrolled participants

The DAIDS Adverse Event Grading Table, Version 2.0, was used for grading of AEs

Outcome measures

Measure	Sitagliptin Arm n=45 Participants Sitagliptin (Januvia) 100 mg one tablet daily p.o. for 16 weeks, followed by a 4-week post-treatment follow-up.	Placebo Arm n=45 Participants Placebo for sitagliptin one tablet daily p.o.for 16 weeks, followed by a 4-week post-treatment follow-up.
Number of Participants With Grade ≥2 Adverse Events Related to Study Drug	3 Participants	0 Participants

Adverse Events

Sitagliptin

Serious events: 1 serious events

Other events: 20 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Measure	Sitagliptin n=45 participants at risk Sitagliptin (Januvia) 100 mg one tablet daily p.o. for 16 weeks, followed by a 4-week post-treatment follow-up.	Placebo n=45 participants at risk Placebo for sitagliptin one tablet daily p.o.for 16 weeks, followed by a 4-week post-treatment follow-up.
Cardiac disorders Acute myocardial infarction	2.2% 1/45 • Adverse Events (AEs) reported from first dose of study treatment until study completion at 20 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.	0.00% 0/45 • Adverse Events (AEs) reported from first dose of study treatment until study completion at 20 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.
Infections and infestations Pneumonia	0.00% 0/45 • Adverse Events (AEs) reported from first dose of study treatment until study completion at 20 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.	2.2% 1/45 • Adverse Events (AEs) reported from first dose of study treatment until study completion at 20 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.
Infections and infestations Upper respiratory tract infection	0.00% 0/45 • Adverse Events (AEs) reported from first dose of study treatment until study completion at 20 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.	2.2% 1/45 • Adverse Events (AEs) reported from first dose of study treatment until study completion at 20 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.

Other adverse events

Measure	Sitagliptin n=45 participants at risk Sitagliptin (Januvia) 100 mg one tablet daily p.o. for 16 weeks, followed by a 4-week post-treatment follow-up.	Placebo n=45 participants at risk Placebo for sitagliptin one tablet daily p.o.for 16 weeks, followed by a 4-week post-treatment follow-up.
Gastrointestinal disorders Nausea	2.2% 1/45 • Adverse Events (AEs) reported from first dose of study treatment until study completion at 20 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.	6.7% 3/45 • Adverse Events (AEs) reported from first dose of study treatment until study completion at 20 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.
General disorders Fatigue	2.2% 1/45 • Adverse Events (AEs) reported from first dose of study treatment until study completion at 20 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.	6.7% 3/45 • Adverse Events (AEs) reported from first dose of study treatment until study completion at 20 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.
General disorders Pyrexia	2.2% 1/45 • Adverse Events (AEs) reported from first dose of study treatment until study completion at 20 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.	6.7% 3/45 • Adverse Events (AEs) reported from first dose of study treatment until study completion at 20 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.
Investigations Alanine aminotransferase	11.1% 5/45 • Adverse Events (AEs) reported from first dose of study treatment until study completion at 20 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.	4.4% 2/45 • Adverse Events (AEs) reported from first dose of study treatment until study completion at 20 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.
Investigations Aspartate aminotransferase	6.7% 3/45 • Adverse Events (AEs) reported from first dose of study treatment until study completion at 20 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.	6.7% 3/45 • Adverse Events (AEs) reported from first dose of study treatment until study completion at 20 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.
Investigations Blood bilirubin increased	6.7% 3/45 • Adverse Events (AEs) reported from first dose of study treatment until study completion at 20 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.	6.7% 3/45 • Adverse Events (AEs) reported from first dose of study treatment until study completion at 20 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.
Investigations Blood creatinine abnormal	8.9% 4/45 • Adverse Events (AEs) reported from first dose of study treatment until study completion at 20 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.	11.1% 5/45 • Adverse Events (AEs) reported from first dose of study treatment until study completion at 20 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.
Investigations Blood glucose decreased	6.7% 3/45 • Adverse Events (AEs) reported from first dose of study treatment until study completion at 20 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.	2.2% 1/45 • Adverse Events (AEs) reported from first dose of study treatment until study completion at 20 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.
Investigations Blood glucose increased	2.2% 1/45 • Adverse Events (AEs) reported from first dose of study treatment until study completion at 20 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.	8.9% 4/45 • Adverse Events (AEs) reported from first dose of study treatment until study completion at 20 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.
Investigations Blood uric acid increased	2.2% 1/45 • Adverse Events (AEs) reported from first dose of study treatment until study completion at 20 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.	6.7% 3/45 • Adverse Events (AEs) reported from first dose of study treatment until study completion at 20 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.
Investigations Haemoglobin decreased	8.9% 4/45 • Adverse Events (AEs) reported from first dose of study treatment until study completion at 20 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.	2.2% 1/45 • Adverse Events (AEs) reported from first dose of study treatment until study completion at 20 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.
Respiratory, thoracic and mediastinal disorders Cough	4.4% 2/45 • Adverse Events (AEs) reported from first dose of study treatment until study completion at 20 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.	6.7% 3/45 • Adverse Events (AEs) reported from first dose of study treatment until study completion at 20 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.

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