NCT00397631

Initial Combination With Pioglitazone Study (0431-064)

Completed Phase 3 Results posted Last updated 12 May 2017

What this trial tests

Phase 3 trial testing sitagliptin 100 mg q.d./pioglitazone 30 mg q.d in Type 2 Diabetes Mellitus in 520 participants. Completed in 28 June 2008.

Timeline

19 December 2006

Primary endpoint
28 June 2008

28 June 2008

Quick facts

Lead sponsor	Merck Sharp & Dohme LLC
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	520
Start date	19 December 2006
Primary completion	28 June 2008
Estimated completion	28 June 2008

Drugs / interventions tested

• sitagliptin 100 mg q.d./pioglitazone 30 mg q.d — full drug profile →
• Comparator: placebo to match sitagliptin 100 mg q.d./pioglitazone 30 mg q.d. — full drug profile →

Conditions studied

• Type 2 Diabetes Mellitus — all drugs for Type 2 Diabetes Mellitus →

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

18 and older, any sex, with Type 2 Diabetes Mellitus. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in HbA1c (Hemoglobin A1C) at Week 24 Primary · Baseline and 24 weeks

HbA1c is measured as a percent. Thus, this change from baseline reflects the Week 24 HbA1c percent minus the Week 0 HbA1c percent.

Group	Value	95% CI
Sitagliptin 100 mg q.d. + Pioglitazone 30 mg q.d.	-2.38	-2.55 – -2.21
Pioglitazone 30 mg q.d.	-1.49	-1.66 – -1.32

Change From Baseline in FPG (Fasting Plasma Glucose) at Week 24 Secondary · Baseline and Week 24

Change from baseline at Week 24 is defined as Week 24 minus Week 0.

Group	Value	95% CI
Sitagliptin 100 mg q.d. + Pioglitazone 30 mg q.d.	-63.0	-68.3 – -57.6
Pioglitazone 30 mg q.d.	-40.2	-45.6 – -34.8

Change From Baseline in 2-hour PPG (Post-prandial Glucose) at Week 24 Secondary · Baseline and Week 24

Change from baseline at Week 24 is defined as Week 24 minus Week 0.

Group	Value	95% CI
Sitagliptin 100 mg q.d. + Pioglitazone 30 mg q.d.	-113.6	-122.4 – -104.8
Pioglitazone 30 mg q.d.	-68.9	-77.8 – -60.0

Adverse events — posted to ClinicalTrials.gov

Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Sitagliptin 100 mg q.d. + Pioglitazone 30 mg q.d.

Serious: 8

Deaths: —

Pioglitazone 30 mg q.d.

Serious: 5

Deaths: —

Serious adverse events (21 terms)

Reaction	System	Sitagliptin 100 mg q.d. + …	Pioglitazone 30 mg q.d.
Any Gastrointestinal disorders	Gastrointestinal disorders	—	—
Any Infections and infestations	Infections and infestations	—	—
Any Nervous system disorders	Nervous system disorders	—	—
Any Ear and labyrinth disorders	Ear and labyrinth disorders	—	—
Acute vestibular syndrome	Ear and labyrinth disorders	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—
Peptic ulcer	Gastrointestinal disorders	—	—
Abscess limb	Infections and infestations	—	—
Bronchitis bacterial	Infections and infestations	—	—
Pulmonary tuberculosis	Infections and infestations	—	—
Any Injury, poisoning and procedural complications	Injury, poisoning and procedural complications	—	—
Foreign body trauma	Injury, poisoning and procedural complications	—	—
Humerus fracture	Injury, poisoning and procedural complications	—	—
Cerebrovascular accident	Nervous system disorders	—	—
Transient ischaemic attack	Nervous system disorders	—	—
Any Psychiatric disorders	Psychiatric disorders	—	—
Impulsive behaviour	Psychiatric disorders	—	—
Any Skin and subcutaneous tissue disorders	Skin and subcutaneous tissue disorders	—	—
Pustular psoriasis	Skin and subcutaneous tissue disorders	—	—
Any Vascular disorders	Vascular disorders	—	—
Peripheral ischaemia	Vascular disorders	—	—

Other adverse events (4 terms — click to expand)

Reaction	System	Sitagliptin 100 mg q.d. + …	Pioglitazone 30 mg q.d.
Any Infections and infestations	Infections and infestations	—	—
Nasopharyngitis	Infections and infestations	—	—
Any Nervous system disorders	Nervous system disorders	—	—
Headache	Nervous system disorders	—	—

Most-reported serious reactions: Any Gastrointestinal disorders, Any Infections and infestations, Any Nervous system disorders, Any Ear and labyrinth disorders, Acute vestibular syndrome, Abdominal pain upper, Peptic ulcer, Abscess limb.

Data from ClinicalTrials.gov NCT00397631 adverse events section.

Sponsor's own description

A clinical study to evaluate the safety and efficacy of the initial combination therapy with sitagliptin and pioglitazone in patients with type 2 diabetes mellitus not on treatment with insulin or oral antihyperglycemic therapy.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

1. Comparative effectiveness of dipeptidylpeptidase-4 inhibitors in type 2 diabetes: a systematic review and mixed treatment comparison.
   Craddy P, Palin HJ, Johnson KI. · · 2014 · cited 85× · PMID 24664619 · DOI 10.1007/s13300-014-0061-3
2. Dipeptidyl peptidase-4 inhibitors and the risk of heart failure: a systematic review and meta-analysis.
   Verma S, Goldenberg RM, Bhatt DL, Farkouh ME, et al · · 2017 · cited 44× · PMID 28459046 · DOI 10.9778/cmajo.20160058
3. Dipeptidyl peptidase-4 inhibitors and fracture risk: an updated meta-analysis of randomized clinical trials.
   Fu J, Zhu J, Hao Y, Guo C, et al · · 2016 · cited 41× · PMID 27384445 · DOI 10.1038/srep29104
4. Efficacy and safety of initial combination therapy with sitagliptin and pioglitazone in patients with type 2 diabetes: a 54-week study.
   Yoon KH, Steinberg H, Teng R, Golm GT, et al · · 2012 · cited 27× · PMID 22405352 · DOI 10.1111/j.1463-1326.2012.01594.x
5. Risk of Fractures Associated with Dipeptidyl Peptidase-4 Inhibitor Treatment: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
   Chen Q, Liu T, Zhou H, Peng H, et al · · 2019 · cited 16× · PMID 31347093 · DOI 10.1007/s13300-019-0668-5