Trial Outcomes & Findings for Study of Sitagliptin for the Treatment of Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Insulin (MK-0431-260) (NCT NCT01462266)

Last Updated: 2018-08-17

Results Overview

Change in daily insulin dose following 24 weeks of therapy (i.e., daily insulin dose at Week 24 minus daily insulin dose at baseline)

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

660 participants

Primary outcome timeframe

Baseline and Week 24

Results posted on

2018-08-17

Participant Flow

Participant milestones

Participant milestones
Measure	Sitagliptin Sitagliptin 100 mg administered orally once daily for 24 weeks.	Placebo Placebo to sitagliptin administered orally once daily for 24 weeks.
Overall Study STARTED	330	330
Overall Study Treated	329	329
Overall Study COMPLETED	295	303
Overall Study NOT COMPLETED	35	27

Reasons for withdrawal

Reasons for withdrawal
Measure	Sitagliptin Sitagliptin 100 mg administered orally once daily for 24 weeks.	Placebo Placebo to sitagliptin administered orally once daily for 24 weeks.
Overall Study Adverse Event	7	6
Overall Study Death	2	1
Overall Study Lack of Efficacy	0	2
Overall Study Lost to Follow-up	4	3
Overall Study Non-compliance with study drug	3	0
Overall Study Creatinine and eGFR, excluded medication	8	4
Overall Study Physician Decision	2	5
Overall Study Protocol Violation	1	3
Overall Study Withdrawal by Subject	7	2
Overall Study Screen failure	1	1

Baseline Characteristics

Study of Sitagliptin for the Treatment of Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Insulin (MK-0431-260)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sitagliptin n=329 Participants Sitagliptin 100 mg administered orally once daily for 24 weeks.	Placebo n=329 Participants Placebo to sitagliptin administered orally once daily for 24 weeks.	Total n=658 Participants Total of all reporting groups
Age, Continuous	59.3 Years STANDARD_DEVIATION 8.9 • n=93 Participants	58.3 Years STANDARD_DEVIATION 9.7 • n=4 Participants	58.8 Years STANDARD_DEVIATION 9.3 • n=27 Participants
Sex: Female, Male Female	178 Participants n=93 Participants	165 Participants n=4 Participants	343 Participants n=27 Participants
Sex: Female, Male Male	151 Participants n=93 Participants	164 Participants n=4 Participants	315 Participants n=27 Participants

PRIMARY outcome

Timeframe: Baseline and Week 24

Population: Full Analysis Set (FAS) population included all randomized participants who took at least one dose of study medication and had at least one measurement either at baseline or post-randomization.

Change in daily insulin dose following 24 weeks of therapy (i.e., daily insulin dose at Week 24 minus daily insulin dose at baseline)

Outcome measures

Outcome measures
Measure	Sitagliptin n=329 Participants Sitagliptin 100 mg administered orally once daily for 24 weeks.	Placebo n=329 Participants Placebo to sitagliptin administered orally once daily for 24 weeks.
Change From Baseline in Daily Insulin Dose at Week 24	19.0 International Units (IU) 95% Confidence Interval 19.6 • Interval 16.5 to 21.6	23.8 International Units (IU) 95% Confidence Interval 24.0 • Interval 21.3 to 26.3

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: FAS population included all randomized participants who took at least one dose of study medication and had at least one measurement either at baseline or post-randomization.

A1C is measured as the percentage of glycosylated hemoglobin. Change in A1C following 24 weeks of therapy (i.e., A1C at Week 24 minus A1C at baseline)

Outcome measures

Outcome measures
Measure	Sitagliptin n=329 Participants Sitagliptin 100 mg administered orally once daily for 24 weeks.	Placebo n=329 Participants Placebo to sitagliptin administered orally once daily for 24 weeks.
Change From Baseline in Hemoglobin A1c (A1C) at Week 24	-1.31 Percent of total hemoglobin 95% Confidence Interval 0.98 • Interval -1.43 to -1.2	-0.87 Percent of total hemoglobin 95% Confidence Interval 1.10 • Interval -0.98 to -0.75

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: FAS population included all randomized participants who took at least one dose of study medication and had at least one measurement either at baseline or post-randomization.

Change in FPG (before breakfast) following 24 weeks of therapy (i.e., FPG at Week 24 minus FPG at baseline)

Outcome measures

Outcome measures
Measure	Sitagliptin n=329 Participants Sitagliptin 100 mg administered orally once daily for 24 weeks.	Placebo n=329 Participants Placebo to sitagliptin administered orally once daily for 24 weeks.
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24	-55.5 mg/dL 95% Confidence Interval 52.0 • Interval -61.1 to -49.9	-44.8 mg/dL 95% Confidence Interval 62.4 • Interval -50.4 to -39.2

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: FAS population included all randomized participants who took at least one dose of study medication, and had at least one post-randomization glycemic goal assessment.

The fasting glucose target was defined as 3 consecutive days with a fingerstick glucose of 72 to 100 mg/dL (4.0 - 5.6 mmol/L).

Outcome measures

Outcome measures
Measure	Sitagliptin n=327 Participants Sitagliptin 100 mg administered orally once daily for 24 weeks.	Placebo n=326 Participants Placebo to sitagliptin administered orally once daily for 24 weeks.
Percent of Participants Achieving Fasting Glucose Target at Any Time During the Study	77.4 Percentage of participants Interval 72.6 to 82.2	74.1 Percentage of participants Interval 69.0 to 79.2

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: FAS population included all randomized participants who took at least one dose of study medication and had at least one post-randomization glycemic goal assessment.

Fasting glucose target 3 consecutive days with a fingerstick glucose of 72 to 100 mg/dL (4.0 - 5.6 mmol/L). This analysis was the Kaplan-Meier estimated 50th percentile of time (days) to first attainment of target.

Outcome measures

Outcome measures
Measure	Sitagliptin n=253 Participants Sitagliptin 100 mg administered orally once daily for 24 weeks.	Placebo n=242 Participants Placebo to sitagliptin administered orally once daily for 24 weeks.
Time to Achieve the Fasting Glucose Target	78 Days to first attainment of target Interval 64.0 to 85.0	90 Days to first attainment of target Interval 80.0 to 107.0

Adverse Events

Sitagliptin

Serious events: 13 serious events

Other events: 121 other events

Deaths: 0 deaths

Placebo

Serious events: 12 serious events

Other events: 168 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Sitagliptin n=329 participants at risk Sitagliptin 100 mg administered orally once daily for 24 weeks.	Placebo n=329 participants at risk Placebo to sitagliptin administered orally once daily for 24 weeks.
Infections and infestations Cellulitis	0.30% 1/329 • Number of events 1 • Up to Week 24 + 14-day follow-up	0.30% 1/329 • Number of events 2 • Up to Week 24 + 14-day follow-up
Infections and infestations Gastroenteritis	0.00% 0/329 • Up to Week 24 + 14-day follow-up	0.30% 1/329 • Number of events 1 • Up to Week 24 + 14-day follow-up
Infections and infestations Herpes zoster	0.00% 0/329 • Up to Week 24 + 14-day follow-up	0.30% 1/329 • Number of events 1 • Up to Week 24 + 14-day follow-up
Infections and infestations Pneumonia	0.00% 0/329 • Up to Week 24 + 14-day follow-up	0.30% 1/329 • Number of events 1 • Up to Week 24 + 14-day follow-up
Infections and infestations Sepsis	0.00% 0/329 • Up to Week 24 + 14-day follow-up	0.30% 1/329 • Number of events 1 • Up to Week 24 + 14-day follow-up
Infections and infestations Subcutaneous abscess	0.30% 1/329 • Number of events 1 • Up to Week 24 + 14-day follow-up	0.00% 0/329 • Up to Week 24 + 14-day follow-up
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/329 • Up to Week 24 + 14-day follow-up	0.30% 1/329 • Number of events 1 • Up to Week 24 + 14-day follow-up
Cardiac disorders Acute coronary syndrome	0.00% 0/329 • Up to Week 24 + 14-day follow-up	0.30% 1/329 • Number of events 1 • Up to Week 24 + 14-day follow-up
Cardiac disorders Acute myocardial infarction	0.00% 0/329 • Up to Week 24 + 14-day follow-up	0.30% 1/329 • Number of events 1 • Up to Week 24 + 14-day follow-up
Cardiac disorders Angina pectoris	0.00% 0/329 • Up to Week 24 + 14-day follow-up	0.30% 1/329 • Number of events 1 • Up to Week 24 + 14-day follow-up
Cardiac disorders Coronary artery disease	0.30% 1/329 • Number of events 1 • Up to Week 24 + 14-day follow-up	0.00% 0/329 • Up to Week 24 + 14-day follow-up
Cardiac disorders Myocardial infarction	0.30% 1/329 • Number of events 1 • Up to Week 24 + 14-day follow-up	0.30% 1/329 • Number of events 1 • Up to Week 24 + 14-day follow-up
General disorders Chest pain	0.30% 1/329 • Number of events 1 • Up to Week 24 + 14-day follow-up	0.00% 0/329 • Up to Week 24 + 14-day follow-up
Immune system disorders Hypersensitivity	0.00% 0/329 • Up to Week 24 + 14-day follow-up	0.30% 1/329 • Number of events 1 • Up to Week 24 + 14-day follow-up
Infections and infestations Appendicitis perforated	0.30% 1/329 • Number of events 1 • Up to Week 24 + 14-day follow-up	0.00% 0/329 • Up to Week 24 + 14-day follow-up
Infections and infestations Tuberculosis	0.00% 0/329 • Up to Week 24 + 14-day follow-up	0.30% 1/329 • Number of events 1 • Up to Week 24 + 14-day follow-up
Injury, poisoning and procedural complications Contusion	0.30% 1/329 • Number of events 1 • Up to Week 24 + 14-day follow-up	0.00% 0/329 • Up to Week 24 + 14-day follow-up
Injury, poisoning and procedural complications Foot fracture	0.00% 0/329 • Up to Week 24 + 14-day follow-up	0.30% 1/329 • Number of events 1 • Up to Week 24 + 14-day follow-up
Injury, poisoning and procedural complications Overdose	0.30% 1/329 • Number of events 1 • Up to Week 24 + 14-day follow-up	0.00% 0/329 • Up to Week 24 + 14-day follow-up
Injury, poisoning and procedural complications Tendon rupture	0.00% 0/329 • Up to Week 24 + 14-day follow-up	0.30% 1/329 • Number of events 1 • Up to Week 24 + 14-day follow-up
Musculoskeletal and connective tissue disorders Monarthritis	0.30% 1/329 • Number of events 1 • Up to Week 24 + 14-day follow-up	0.00% 0/329 • Up to Week 24 + 14-day follow-up
Nervous system disorders Hemiparesis	0.30% 1/329 • Number of events 1 • Up to Week 24 + 14-day follow-up	0.00% 0/329 • Up to Week 24 + 14-day follow-up
Reproductive system and breast disorders Spermatocele	0.30% 1/329 • Number of events 1 • Up to Week 24 + 14-day follow-up	0.00% 0/329 • Up to Week 24 + 14-day follow-up
Respiratory, thoracic and mediastinal disorders Status asthmaticus	0.30% 1/329 • Number of events 1 • Up to Week 24 + 14-day follow-up	0.00% 0/329 • Up to Week 24 + 14-day follow-up
Skin and subcutaneous tissue disorders Ingrowing nail	0.30% 1/329 • Number of events 1 • Up to Week 24 + 14-day follow-up	0.00% 0/329 • Up to Week 24 + 14-day follow-up
Vascular disorders Hypertensive crisis	0.30% 1/329 • Number of events 1 • Up to Week 24 + 14-day follow-up	0.00% 0/329 • Up to Week 24 + 14-day follow-up

Other adverse events

Other adverse events
Measure	Sitagliptin n=329 participants at risk Sitagliptin 100 mg administered orally once daily for 24 weeks.	Placebo n=329 participants at risk Placebo to sitagliptin administered orally once daily for 24 weeks.
Gastrointestinal disorders Diarrhoea	5.2% 17/329 • Number of events 19 • Up to Week 24 + 14-day follow-up	3.3% 11/329 • Number of events 11 • Up to Week 24 + 14-day follow-up
Infections and infestations Nasopharyngitis	4.0% 13/329 • Number of events 16 • Up to Week 24 + 14-day follow-up	7.9% 26/329 • Number of events 29 • Up to Week 24 + 14-day follow-up
Infections and infestations Urinary tract infection	4.3% 14/329 • Number of events 16 • Up to Week 24 + 14-day follow-up	5.2% 17/329 • Number of events 18 • Up to Week 24 + 14-day follow-up
Metabolism and nutrition disorders Hypoglycaemia	28.3% 93/329 • Number of events 358 • Up to Week 24 + 14-day follow-up	43.8% 144/329 • Number of events 794 • Up to Week 24 + 14-day follow-up

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the sponsor as confidential must be deleted prior to submission.
Publication restrictions are in place

Restriction type: OTHER