NCT00395343

Sitagliptin Added-on to Insulin Study (0431-051)

Completed Phase 3 Results posted Last updated 12 May 2017

What this trial tests

Phase 3 trial testing sitagliptin phosphate in Type 2 Diabetes Mellitus in 641 participants. Completed in 13 October 2008.

Timeline

11 December 2006

Primary endpoint
13 October 2008

13 October 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	641
Start date	11 December 2006
Primary completion	13 October 2008
Estimated completion	13 October 2008

Drugs / interventions tested

• sitagliptin phosphate — full drug profile →
• Comparator : placebo (unspecified)

Conditions studied

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

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

21 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 A1C at Week 24 Primary · Baseline and Week 24

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

Group	Value	95% CI
Sitagliptin 100 mg q.d.	-0.59	-0.70 – -0.48
Placebo	-0.03	-0.14 – 0.08

Change From Baseline in Fasting Plasma Glucose (FPG) 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.	-18.5	-25.1 – -11.9
Placebo	-3.5	-10.2 – 3.1

Change From Baseline in 2-hour Post-meal Glucose (PMG) 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.	-30.9	-40.0 – -21.8
Placebo	5.2	-3.6 – 13.9

Percent Change From Baseline in Index of Static Beta-Cell Sensitivity to Glucose at Week 24 Secondary · Baseline and Week 24

Static sensitivity is a measure of the effect of glucose on beta-cell secretion and is the ratio between the insulin secretion rate and glucose concentration above the threshold level at steady state. (See Breda and Cobelli, Annals of Biomedical Engineering 29, 692-700 (2001) for more details.)

Group	Value	95% CI
Sitagliptin 100 mg q.d.	28.4	5.4 – 56.6
Placebo	-8.1	-22.6 – 9.2

Percent of Patients With A1C < 7.0% at Week 24 Secondary · 24 Weeks

Group	Value	95% CI
Sitagliptin 100 mg q.d.	12.8
Placebo	5.1

Percent of Patients With A1C < 6.5% at Week 24 Secondary · Week 24

Group	Value	95% CI
Sitagliptin 100 mg q.d.	2.3
Placebo	1.9

Change From Baseline in A1C at Week 24 Secondary · Baseline and Week 24

A1C in subset of patients on long-acting or intermediate-acting insulin. A1C is measured as a percent. Thus, this change from baseline reflects the Week 24 A1C percent minus the Week 0 A1C percent.

Group	Value	95% CI
Sitagliptin 100 mg q.d.	-0.61	-0.73 – -0.48
Placebo	-0.04	-0.16 – 0.08

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.

Serious: 20/322 (6%)

Deaths: —

Placebo

Serious: 11/319 (3%)

Deaths: —

Serious adverse events (46 terms)

Reaction	System	Sitagliptin 100 mg q.d.	Placebo
Any Cardiac disorders	Cardiac disorders	—	—
Any Infections and Infestations	Infections and infestations	—	—
Angina pectoris	Cardiac disorders	—	—
Cardiac failure congestive	Cardiac disorders	—	—
Any Gastrointestinal Disorders	Gastrointestinal disorders	—	—
Any Injury, Poisoning and Procedural Complications	Injury, poisoning and procedural complications	—	—
Any Metabolism and nutrition disorders	Metabolism and nutrition disorders	—	—
Hypoglycaemia	Metabolism and nutrition disorders	—	—
Any Neoplasms Benign, Malignant and Unspecified (Incl Cysts and Polyps)	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Any Nervous System Disorders	Nervous system disorders	—	—
Any Skin and Subcutaneous Tissue Disorders	Skin and subcutaneous tissue disorders	—	—
Acute myocardial infarction	Cardiac disorders	—	—
Angina unstable	Cardiac disorders	—	—
Coronary artery disease	Cardiac disorders	—	—
Myocardial infarction	Cardiac disorders	—	—
Trifascicular block	Cardiac disorders	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Inguinal hernia	Gastrointestinal disorders	—	—
Oesophageal spasm	Gastrointestinal disorders	—	—
Any Hepatobiliary disorders	Hepatobiliary disorders	—	—
Cholecystitis acute	Hepatobiliary disorders	—	—
Cholelithiasis obstructive	Hepatobiliary disorders	—	—
Bronchitis	Infections and infestations	—	—
Genital abscess	Infections and infestations	—	—
Perianal abscess	Infections and infestations	—	—

Other adverse events (2 terms — click to expand)

Reaction	System	Sitagliptin 100 mg q.d.	Placebo
Any Metabolism and nutrition disorders	Metabolism and nutrition disorders	—	—
Hypoglycaemia	Metabolism and nutrition disorders	—	—

Most-reported serious reactions: Any Cardiac disorders, Any Infections and Infestations, Angina pectoris, Cardiac failure congestive, Any Gastrointestinal Disorders, Any Injury, Poisoning and Procedural Complications, Any Metabolism and nutrition disorders, Hypoglycaemia.

Data from ClinicalTrials.gov NCT00395343 adverse events section.

Sponsor's own description

A clinical study to determine the safety and efficacy of sitagliptin in patients with Type 2 Diabetes Mellitus who have inadequate glycemic control on insulin or insulin/metformin combination therapy.

Publications & conference data

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

1. Dipeptidyl peptidase-4 inhibitors and risk of heart failure in type 2 diabetes: systematic review and meta-analysis of randomised and observational studies.
   Li L, Li S, Deng K, Liu J, et al · · 2016 · cited 157× · PMID 26888822 · DOI 10.1136/bmj.i610
2. 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
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. 53 &lt;sup&gt;rd&lt;/sup&gt; EASD Annual Meeting of the European Association for the Study of Diabetes : Lisbon, Portugal, 11 - 15 September 2017.
   · 2017 · cited 17× · PMID 28795195 · DOI 10.1007/s00125-017-4350-z
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