NCT01477853

A Study of the Co-administration of Sitagliptin and Atorvastatin in Inadequately Controlled Type 2 Diabetes Mellitus (MK-0431E-211)

Terminated Phase 3 Results posted Last updated 26 July 2018

What this trial tests

Phase 3 trial testing Sitagliptin in Type 2 Diabetes Mellitus in 166 participants. Terminated before completion.

Timeline

24 October 2011

Primary endpoint
4 December 2012

4 December 2012

Quick facts

Lead sponsor	Merck Sharp & Dohme LLC
Phase	Phase 3
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	166
Start date	24 October 2011
Primary completion	4 December 2012
Estimated completion	4 December 2012

Drugs / interventions tested

• Sitagliptin (SITAGLIPTIN) — full drug profile →
• Atorvastatin (atorvastatin) — full drug profile →
• Placebo to sitagliptin
• Placebo to atorvastatin
• Metformin (open-label) — full drug profile →
• Glimepiride (open-label) — full drug profile →
• Glimepiride (double-blind)
• Placebo to glimepiride — 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

Adults 18 to 79, 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 16 Primary · Baseline and Week 16

A1C is measured as percent. Thus, this change from baseline reflects the Week 16 A1C percent minus the Week 0 A1C percent.

Group	Value	95% CI
Sitagliptin/Sitagliptin + Atorvastatin	-1.17	± 0.20
Atorvastatin/Atorvastatin + Glimepiride	0.04	± 0.31
Sitagliptin + Atorvastatin/Sitagliptin + Atorvastatin	-1.01	± 0.22

Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 16 Primary · Baseline and Week 16

Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.

Group	Value	95% CI
Sitagliptin/Sitagliptin + Atorvastatin	4.9	± 10.4
Atorvastatin/Atorvastatin + Glimepiride	-35.7	± 7.1
Sitagliptin + Atorvastatin/Sitagliptin + Atorvastatin	-38.7	± 6.6

Change From Baseline in Fasting Plasma Glucose (FPG) at Week 16 Secondary · Baseline and Week 16

Change from baseline reflects the Week 16 value minus the Week 0 value.

Group	Value	95% CI
Sitagliptin/Sitagliptin + Atorvastatin	-15.7	± 6.4
Atorvastatin/Atorvastatin + Glimepiride	22.7	± 10.1
Sitagliptin + Atorvastatin/Sitagliptin + Atorvastatin	-26.0	± 14.0

Percent Change From Baseline in Total Cholesterol at Week 16 Secondary · Baseline and Week 16

Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.

Group	Value	95% CI
Sitagliptin/Sitagliptin + Atorvastatin	-1.7	± 6.2
Atorvastatin/Atorvastatin + Glimepiride	-28.3	± 4.8
Sitagliptin + Atorvastatin/Sitagliptin + Atorvastatin	-25.7	± 6.0

Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 16 Secondary · Baseline and Week 16

Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.

Group	Value	95% CI
Sitagliptin/Sitagliptin + Atorvastatin	-4.8	± 6.5
Atorvastatin/Atorvastatin + Glimepiride	-32.9	± 5.6
Sitagliptin + Atorvastatin/Sitagliptin + Atorvastatin	-29.0	± 4.6

Percent Change From Baseline in Non-high Density Lipoprotein Cholesterol (Non-HDL-C) at Week 16 Secondary · Baseline and Week 16

Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.

Group	Value	95% CI
Sitagliptin/Sitagliptin + Atorvastatin	-1.0	± 8.8
Atorvastatin/Atorvastatin + Glimepiride	-34.4	± 6.7
Sitagliptin + Atorvastatin/Sitagliptin + Atorvastatin	-34.6	± 6.7

Percent Change From Baseline in Triglycerides at Week 16 Secondary · Baseline and Week 16

Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.

Group	Value	95% CI
Sitagliptin/Sitagliptin + Atorvastatin	-9.9	± 8.6
Atorvastatin/Atorvastatin + Glimepiride	-28.7	± 6.5
Sitagliptin + Atorvastatin/Sitagliptin + Atorvastatin	-10.5	± 13.5

Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C) at Week 16 Secondary · Baseline and Week 16

Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.

Group	Value	95% CI
Sitagliptin/Sitagliptin + Atorvastatin	-15.5	± 7.2
Atorvastatin/Atorvastatin + Glimepiride	-28.6	± 6.6
Sitagliptin + Atorvastatin/Sitagliptin + Atorvastatin	-10.4	± 13.5

Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 16 Secondary · Baseline and Week 16

Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.

Group	Value	95% CI
Sitagliptin/Sitagliptin + Atorvastatin	-0.3	± 3.2
Atorvastatin/Atorvastatin + Glimepiride	-5.8	± 3.5
Sitagliptin + Atorvastatin/Sitagliptin + Atorvastatin	1.5	± 6.0

Number of Participants Who Experienced at Least One Adverse Event Primary · Up to 56 weeks (including 2-week follow-up)

An adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the investigational product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the investigational product, is also an adverse event. Data presented exclude data following the initiation of glycemic rescue therapy.

Group	Value	95% CI
Sitagliptin/Sitagliptin + Atorvastatin	10
Atorvastatin/Atorvastatin + Glimepiride	13
Sitagliptin + Atorvastatin/Sitagliptin + Atorvastatin	13

Number of Participants Who Discontinued Study Drug Due to an Adverse Event Primary · Up to 54 weeks

An adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the investigational product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the investigational product, is also an adverse event. Data presented exclude data following the initiation of glycemic rescue therapy.

Group	Value	95% CI
Sitagliptin/Sitagliptin + Atorvastatin	1
Atorvastatin/Atorvastatin + Glimepiride	2
Sitagliptin + Atorvastatin/Sitagliptin + Atorvastatin	2

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 56 weeks including 2-week follow-up (up to 56 weeks for serious adverse events, up to 54 weeks for non-serious adverse events). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Sitagliptin/Sitagliptin + Atorvastatin

Serious: 0/55 (0%)

Deaths: —

Atorvastatin/Atorvastatin + Glimepiride

Serious: 0/56 (0%)

Deaths: —

Sitagliptin + Atorvastatin/Sitagliptin + Atorvastatin

Serious: 1/55 (2%)

Deaths: —

Serious adverse events (1 terms)

Reaction	System	Sitagliptin/Sitagliptin + …	Atorvastatin/Atorvastatin …	Sitagliptin + Atorvastatin…
Inguinal hernia	Gastrointestinal disorders	—	—	—

Other adverse events (2 terms — click to expand)

Reaction	System	Sitagliptin/Sitagliptin + …	Atorvastatin/Atorvastatin …	Sitagliptin + Atorvastatin…
Intentional overdose	Injury, poisoning and procedural complications	—	—	—
Glomerular filtration rate decreased	Investigations	—	—	—

Most-reported serious reactions: Inguinal hernia.

Data from ClinicalTrials.gov NCT01477853 adverse events section.

Sponsor's own description

This two-phase study was to examine if 16 weeks of treatment with sitagliptin in combination with atorvastatin reduces hemoglobin A1C (A1C) and low density lipoprotein cholesterol (LDL-C) from baseline more than atorvastatin alone and sitagliptin alone, respectively. Following a single-blind placebo run-in period, participants were to be randomized to one of three treatment arms (sitagliptin monotherapy, atorvastatin monotherapy, or sitagliptin plus atorvastatin) for 16 weeks (Phase A). During Phase B of the study (Weeks 16 through 54), participants were to receive either sitagliptin plus atorvastatin or glimepiride plus atorvastatin. The primary hypotheses were that after 16 weeks of treatment, sitagliptin in combination with atorvastatin reduces A1C from baseline more than atorvastatin alone, and that atorvastatin in combination with sitagliptin lowers LDL-C from baseline more than sitagliptin alone.

Publications & conference data

No peer-reviewed publications indexed yet for this trial.