NCT01076088

Safety and Efficacy of Co-Administration of Sitagliptin and Metformin in China (MK-0431-121)

Completed Phase 3 Results posted Last updated 23 May 2017

What this trial tests

Phase 3 trial testing Sitagliptin 50 mg in Type 2 Diabetes Mellitus in 744 participants. Completed in 24 December 2012.

Timeline

15 November 2010

Primary endpoint
24 December 2012

24 December 2012

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	744
Start date	15 November 2010
Primary completion	24 December 2012
Estimated completion	24 December 2012

Drugs / interventions tested

• Sitagliptin 50 mg — full drug profile →
• Metformin 500 mg
• Sitagliptin 100 mg — full drug profile →
• Placebo
• Metformin 850 mg

Conditions studied

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

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

Adults 18 to 78, 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 Hemoglobin A1C (A1C) at Week 24 Primary · Baseline and Week 24

A1C is measured as percent. Thus, this change from baseline reflects the Week 24 A1C percent minus the Week 0 A1C percent.

Group	Value	95% CI
Sitagliptin 50 mg + Metformin 500 mg	-1.67	-1.92 – -1.43
Sitagliptin 50 mg + Metformin 850 mg	-1.83	-2.07 – -1.58
Metformin 500 mg	-1.29	-1.54 – -1.04
Metformin 850 mg	-1.56	-1.80 – -1.32
Sitagliptin 100 mg	-0.99	-1.24 – -0.75
Placebo	-0.59	-0.84 – -0.34

Change From Baseline in 2-hour Post Meal Glucose (2-h PMG) at Week 24 Secondary · Baseline and Week 24

Change from baseline in 2-h PMG at Week 24 is defined as Week 24 2-h PMG minus Week 0 2-h PMG.

Group	Value	95% CI
Sitagliptin 50 mg + Metformin 500 mg	-97.05	-109.01 – -85.09
Sitagliptin 50 mg + Metformin 850 mg	-109.46	-121.47 – -97.44
Metformin 500 mg	-65.67	-77.76 – -53.58
Metformin 850	-90.93	-103.04 – -78.83
Sitagliptin 100 mg	-48.11	-60.37 – -35.85
Placebo	-21.88	-34.33 – -9.43

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

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

Group	Value	95% CI
Sitagliptin 50 mg + Metformin 500 mg	-39.38	-46.29 – -32.47
Sitagliptin 50 mg + Metformin 850 mg	-47.74	-54.73 – -40.75
Metformin 500 mg	-33.66	-40.66 – -26.66
Metformin 850	-39.63	-46.50 – -32.76
Sitagliptin 100 mg	-21.86	-28.92 – -14.80
Placebo	-11.93	-18.94 – -4.92

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 50 mg + Metformin 500 mg

Serious: 0/122 (0%)

Deaths: —

Sitagliptin 50 mg + Metformin 850 mg

Serious: 0/125 (0%)

Deaths: —

Metformin 500 mg

Serious: 1/126 (1%)

Deaths: —

Metformin 850

Serious: 1/124 (1%)

Deaths: —

Sitagliptin 100 mg

Serious: 3/120 (3%)

Deaths: —

Placebo

Serious: 1/126 (1%)

Deaths: —

Serious adverse events (10 terms)

Reaction	System	Sitagliptin 50 mg + Metfor…	Sitagliptin 50 mg + Metfor…	Metformin 500 mg	Metformin 850	Sitagliptin 100 mg	Placebo
Coagulopathy	Blood and lymphatic system disorders	—	—	—	—	—	—
Femur fracture	Injury, poisoning and procedural complications	—	—	—	—	—	—
Lumbar vertebral fracture	Injury, poisoning and procedural complications	—	—	—	—	—	—
Thoracic vertebral fracture	Injury, poisoning and procedural complications	—	—	—	—	—	—
Coagulation time shortened	Investigations	—	—	—	—	—	—
Transaminases increased	Investigations	—	—	—	—	—	—
Renal cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—
Cerebral infarction	Nervous system disorders	—	—	—	—	—	—
Subarachnoid haemorrhage	Nervous system disorders	—	—	—	—	—	—
Lung infection	Infections and infestations	—	—	—	—	—	—

Other adverse events (3 terms — click to expand)

Reaction	System	Sitagliptin 50 mg + Metfor…	Sitagliptin 50 mg + Metfor…	Metformin 500 mg	Metformin 850	Sitagliptin 100 mg	Placebo
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—
Hypoglycaemia	Metabolism and nutrition disorders	—	—	—	—	—	—

Most-reported serious reactions: Coagulopathy, Femur fracture, Lumbar vertebral fracture, Thoracic vertebral fracture, Coagulation time shortened, Transaminases increased, Renal cancer, Cerebral infarction.

Data from ClinicalTrials.gov NCT01076088 adverse events section.

Sponsor's own description

This study will assess the efficacy and safety of initial treatment with sitagliptin and metformin in patients with type 2 diabetes mellitus in China. The primary hypothesis is that after 24 weeks, initial co-administration treatment with sitagliptin and metformin provided greater reduction in hemoglobin A1C (A1C) compared to initial treatment with sitagliptin alone and with metformin alone.

Publications & conference data

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

1. Dipeptidyl peptidase-4 inhibitors and cancer risk in patients with type 2 diabetes: a meta-analysis of randomized clinical trials.
   Zhao M, Chen J, Yuan Y, Zou Z, et al · · 2017 · cited 50× · PMID 28811622 · DOI 10.1038/s41598-017-07921-2
2. 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
3. The effects of dipeptidyl peptidase-4 inhibitors on bone fracture among patients with type 2 diabetes mellitus: A network meta-analysis of randomized controlled trials.
   Yang J, Huang C, Wu S, Xu Y, et al · · 2017 · cited 37× · PMID 29206832 · DOI 10.1371/journal.pone.0187537
4. Randomized clinical trial of the safety and efficacy of sitagliptin and metformin co-administered to Chinese patients with type 2 diabetes mellitus.
   Ji L, Han P, Wang X, Liu J, et al · · 2016 · cited 28× · PMID 27181998 · DOI 10.1111/jdi.12511
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
6. Differential HbA1c response in the placebo arm of DPP-4 inhibitor clinical trials conducted in China compared to other countries: a systematic review and meta-analysis.
   He L, Liu S, Shan C, Tu Y, et al · · 2016 · cited 4× · PMID 27600598 · DOI 10.1186/s40360-016-0084-7
7. Risk of diarrhea in patients with type 2 diabetes mellitus treated with sitagliptin: a meta-analysis of 30 randomized clinical trials.
   Zhao Q, Hong D, Zheng D, Xiao Y, et al · · 2014 · cited 3× · PMID 25419118 · DOI 10.2147/dddt.s70945