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Type 2 Diabetes MellitusPhase 3NCT01986881

Cardiovascular Outcomes Following Ertugliflozin Treatment in Type 2 Diabetes Mellitus Participants With Vascular Disease, The VERTIS CV Study (MK-8835-004)

A Phase 3 study testing Ertugliflozin and Glycemic Rescue in people with Type 2 Diabetes Mellitus, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

An overall study of the cardiovascular outcomes following treatment with ertugliflozin in participants with type 2 diabetes mellitus (T2DM) and established vascular disease. The main objective of this study is to assess the cardiovascular safety of ertugliflozin. Read more about this study

Who is it for?
Ages 40 years and older
Conditions the study is for
Type 2 Diabetes Mellitus
What is being tested?
Ertugliflozin and Glycemic Rescue
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
8,246 participants
Where
No sites listed yet
Study dates
4 Nov 2013to 27 Dec 2019
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 40 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diagnosis of T2DM in accordance with American Diabetes Association (ADA) guidelines
  • Hemoglobin A1c (A1C) at the start of study participation of 7.0-10.5% (53-91 mmol/mol)
  • On stable allowable anti-hyperglycemic agents (AHA) or on no background AHA for at least 8 weeks prior to the study participation
  • Body Mass Index (BMI) > or = to 18.0 kg/m^2
  • Evidence or a history of atherosclerosis involving the coronary, cerebral or peripheral vascular systems
  • There is adequate documentation of the objective evidence that the participant has established vascular disease such as investigational site's medical records, copies of such records from other institutions, or a letter from a referring physician that specifically states the diagnosis and date of the most recent occurrence of the qualifying event(s) or procedure(s).
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  • Male, female not or reproductive potential, or female of reproductive potential who agrees to be abstinent from heterosexual activity or agrees to use or have their partner use 2 acceptable methods of contraception
  • Insulin With or Without Metformin Sub-study: Stable doses of insulin (>=20 units/day, with variations up to 10% in the daily dose permitted) with or without metformin (>=1500 mg/day) for at least 8 weeks prior to the time of the Screening Visit (V1) and during the period between the Screening Visit (V1) and randomization.
  • Sulfonylurea (SU) Monotherapy Sub-study: Participants receiving a stable dose of SU monotherapy for at least 8 weeks prior to the time of the Screening Visit (V1) and during the period between the Screening Visit (V1) and randomization.
  • Metformin with SU Sub-study: Participants receiving a stable dose metformin (≥1500 mg/day) with a SU for at least 8 weeks prior to the time of the Screening Visit (V1) and during the period between the Screening Visit (V1) and randomization.

Who cannot join

  • Previous randomization into this trial
  • Experiencing a cardiovascular event (myocardial infarction or stroke) or undergoing coronary angioplasty or peripheral intervention procedure between the Screening Visit and randomization
  • Undergoing any cardiovascular surgery (valvular surgery) within 3 months of study participation
  • Planned revascularization or peripheral intervention procedure or other cardiovascular surgery
  • New York Heart Association (NYHA) IV heart failure at study participation
  • History of type 1 diabetes mellitus or a history of ketoacidosis

About this study

Official title: Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Assess Cardiovascular Outcomes Following Treatment With Ertugliflozin (MK-8835/PF-04971729) in Subjects With Type 2 Diabetes Mellitus and Established Vascular Disease, The VERTIS CV Study

An overall study of the cardiovascular outcomes following treatment with ertugliflozin in participants with type 2 diabetes mellitus (T2DM) and established vascular disease. The main objective of this study is to assess the cardiovascular safety of ertugliflozin. This trial includes 3 pre-defined glycemic sub-studies; 1. In participants receiving background insulin with or without metformin, 2. In participants receiving background sulfonylurea monotherapy, and 3. In participants receiving background metformin with sulfonylurea (all fully-enrolled).

Participants enrolled prior to Amendment 1 were in the overall study as well as a sub-study, if they met certain entry criteria. Participants enrolled following the start of Amendment 1 were only enrolled in the overall study. The sub-studies were the initial 18 weeks of the overall study period.

Read the detailed description

The primary hypotheses for the 4 studies are:

  1. Overall Cardiovascular Study: The time to first occurrence of the composite endpoint of MACE: cardiovascular death, non-fatal myocardial infarction [MI] or non-fatal stroke in participants treated with ertugliflozin is non-inferior compared to that in participants treated with placebo.
  2. The 3 Glycemic Sub-studies:
  3. The mean reduction from baseline in hemoglobin A1c (A1C) for 15 mg ertugliflozin is greater than that for placebo.
  4. The mean reduction from baseline in A1C for 5 mg ertugliflozin is greater than that for placebo.
Being tested
Ertugliflozin, Placebo, Glycemic Rescue
Medical subject headings
Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ErtugliflozinDrug

    Also called MK-8835, PF-04971729, Steglatro

    Oral, once daily, for up to approximately 6 years

  • PlaceboDrug

    Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years

  • Glycemic RescueDrug

    Doses of background anti-hyperglycemic agents (AHA), medications will be required to be held constant in all participants enrolled for the initial 18 weeks of the trial with 2 exceptions: First, participant will be prescribed glycemic rescue therapy if they meet specific, progressively more stringent, glycemic thresholds based on repeated, confirmed fasting plasma glucose (FPG) measured at a central laboratory. Second, a participant experiencing clinically significant hypoglycemia according to the investigator at any time during the trial is permitted to have the dose of appropriate background AHA (e.g., insulin, sulfonylurea [SU], glinide) reduced or discontinued as per the judgment of the investigator or the treating physician. Choice and dosing of glycemic rescue will be at the discretion of the investigator or the treating physician consistent with standards of care for management of patients with Type 2 diabetes mellitus (T2DM) within the country of the investigational site.

Study groups in NCT01986881
Study groupRoleWhat they receive
Ertugliflozin, 15 mgExperimentalErtugliflozin 15 mg administered orally once daily for up to approximately 6 years
Receives: Drug: Ertugliflozin; Drug: Glycemic Rescue
Ertugliflozin, 5 mgExperimentalErtugliflozin 5 mg administered orally once daily for up to approximately 6 years
Receives: Drug: Ertugliflozin; Drug: Placebo; Drug: Glycemic Rescue
PlaceboPlacebo comparatorMatching placebo to ertugliflozin administered orally once daily for up to approximately 6 years
Receives: Drug: Placebo; Drug: Glycemic Rescue

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Time to First Occurrence of MACE (Composite Endpoint of Major Adverse Cardiovascular Events [Cardiovascular Death, Non-fatal Myocardial Infarction or Non-fatal Stroke]) (On-Treatment + 365-day Approach) (Overall Cardiovascular Study)

    Time to the first occurrence of any of the following adjudicated components of the primary composite endpoint (3-point major adverse cardiovascular events (MACE)): cardiovascular (CV) death (including fatal stroke and fatal myocardial infarction (MI)), non-fatal MI, and non-fatal stroke. The on-treatment approach included confirmed events that occurred between the date of first dose of study medication and the on-treatment censor date. Person-years was calculated as the sum of participants' time to first event or time to censoring (the earliest of participants' end of study date, death date, last contact date, or 365 days after the last dose).

    Measured: Up to approximately 6 years

  2. Baseline Hemoglobin A1C (A1C) (Insulin With or Without Metformin Add-on Glycemic Sub-study)

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This baseline reflects the Week 0 A1C.

    Measured: Baseline

  3. Change From Baseline in Hemoglobin A1C (A1C) at Week 18 - Excluding Rescue Approach (Insulin With or Without Metformin Add-on Glycemic Sub-study)

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This change from baseline reflects the Week 18 A1C minus the Week 0 A1C. A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

    Measured: Baseline and Week 18

  4. Baseline Hemoglobin A1C (A1C) (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This baseline reflects the Week 0 A1C.

    Measured: Baseline

  5. Change From Baseline in Hemoglobin A1C (A1C) at Week 18 - Excluding Rescue Approach (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This change from baseline reflects the Week 18 A1C minus the Week 0 A1C. A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

    Measured: Baseline and Week 18

  6. Baseline Hemoglobin A1C (A1C) (Metformin With Sulfonylurea Add-on Glycemic Sub-study)

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This baseline reflects Week 0 A1C.

    Measured: Baseline

  7. Change From Baseline in Hemoglobin A1C (A1C) at Week 18 - Excluding Rescue Approach (Metformin With Sulfonylurea Add-on Glycemic Sub-study)

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This change from baseline reflects the Week 18 A1C minus the Week 0 A1C. A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

    Measured: Baseline and Week 18

Secondary outcomes (119)

  1. Time to Occurrence of Cardiovascular (CV) Death or Hospitalization for Heart Failure (HHF) (On-Study Approach) (Overall Cardiovascular Study)

    Time to the occurrence of any of the following adjudicated components of cardiovascular (CV) death (including fatal stroke and fatal myocardial infarction (MI)) or hospitalization for heart failure. The on-study approach included confirmed events that occurred between the randomization date and the on-study censor date. Person-years was calculated as the sum of participants' time to event or time to censoring (the earliest of participants' end of study date, death date, or last contact date).

    Measured: Up to approximately 6 years

  2. Time to Occurrence of Cardiovascular Death (On-study Approach) (Overall Cardiovascular Study)

    Time to the occurrence of cardiovascular (CV) death (including fatal stroke and fatal myocardial infarction (MI)). The on-study approach included confirmed events that occurred between the randomization date and the on-study censor date. Person-years was calculated as the sum of participants' time to CV death or time to censoring (the earliest of participants' end of study date or date last known to be alive).

    Measured: Up to approximately 6 years

  3. Time to First Occurrence of the Renal Composite: the Composite of Renal Death, Renal Dialysis/Transplant, or Doubling of Serum Creatinine From Baseline (On-Study Approach) (Overall Cardiovascular Study)

    Renal composite endpoint was defined as a composite of renal death, renal dialysis/transplant, or doubling of serum creatinine from baseline. The on-study approach included events that occurred between the randomization date and the on-study censor date. Person-years was calculated as the sum of participants' time to first event or time to censoring (the earliest of participants' end of study date, death date, or last contact date). The on-study approach included events that occurred between the randomization date and the on-study censor date.

    Measured: Up to approximately 6 years

  4. Time to First Occurrence of MACE Plus (Composite Endpoint of Cardiovascular Death, Non-fatal Myocardial Infarction, Non-fatal Stroke or Hospitalization for Unstable Angina) (On-Study Approach) (Overall Cardiovascular Study)

    Time to the first occurrence of any of the following adjudicated components 4-point MACE: cardiovascular death (including fatal stroke and fatal myocardial infarction), non-fatal myocardial infarction, non-fatal stroke, and hospitalization for unstable angina pectoris. The on-study approach included confirmed events that occurred between the randomization date and the on-study censor date. Person-years was calculated as the sum of participants' time to first event or time to censoring (the earliest of participants' end of study date, death date, or last contact date). The on-study approach included events that occurred between the randomization date and the on-study censor date.

    Measured: Up to approximately 6 years

  5. Time to First Occurrence of Fatal or Non-fatal Myocardial Infarction (On-Study Approach) (Overall Cardiovascular Study)

    Time to First Occurrence of Fatal or Non-fatal Myocardial Infarction. The on-study approach included confirmed events that occurred between the randomization date and the on-study censor date. Person-years was calculated as the sum of participants' time to first event or time to censoring (the earliest of participants' end of study date, death date, or last contact date).

    Measured: Up to approximately 6 years

  6. Time to First Occurrence of Fatal or Non-fatal Stroke (FNF Stroke) (On-Study Approach) (Overall Cardiovascular Study)

    Time to the first occurrence of fatal and no-fatal stroke. The on-study approach included confirmed events that occurred between the randomization date and the on-study censor date. Person-years was calculated as the sum of participants' time to first event or time to censoring (the earliest of participants' end of study date, death date, or last contact date). The on-study approach included events that occurred between the randomization date and the on-study censor date.

    Measured: Up to approximately 6 years

  7. Time to First Occurrence of Hospitalization for Heart Failure (HHF) (On-Study Approach) (Overall Cardiovascular Study)

    Time to the first occurrence of heart failure requiring hospitalization (adjudicated). The on-study approach included confirmed events that occurred between the randomization date and the on-study censor date. Person-years was calculated as the sum of participants' time to first event or time to censoring (the earliest of participants' end of study date, death date, or last contact date). The on-study approach included events that occurred between the randomization date and the on-study censor date.

    Measured: Up to approximately 6 years

  8. Time to Occurrence of Death From Any Cause (On-Study Approach) (Overall Cardiovascular Study)

    Time to the occurrence of death from any cause. The on-study approach included confirmed events that occurred between the randomization date and the on-study censor date. Person-years was calculated as the sum of participants' time to event or time to censoring (the earliest of participants' end of study date, death date, last contact date, or date last known to be alive. The on-study approach included events that occurred between the randomization date and the on-study censor date.

    Measured: Up to approximately 6 years

  9. Andersen-Gill Model for Total MACE (On-Study Approach) (Overall Cardiovascular Study)

    All events (first and recurrent) of the composite of MACE (3-point major adverse cardiovascular events: cardiovascular (CV) death (including fatal stroke and fatal myocardial infarction (MI)), non-fatal MI, and non-fatal stroke) were assessed using Andersen-Gill model. The on-study approach included events that occurred between the randomization date and the on-study censor date.

    Measured: Up to approximately 6 years

  10. Andersen-Gill Model for All Cardiovascular Death (CV Death) or Hospitalizations for Heart Failure (HFF) (On-Study Approach) (Overall Cardiovascular Study)

    All events (first and recurrent) of the composite of CV death and HHF were assessed using an Andersen-Gill model. Person-years were calculated as the sum of time from randomization to end of follow-up. The on-study approach included events that occurred between the randomization date and the on-study censor date.

    Measured: Up to approximately 6 years

  11. Change From Baseline in Hemoglobin A1C (A1C) at Week 18 - Excluding Rescue Approach (Overall Cardiovascular Study)

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This change from baseline reflects the Week 18 A1C minus the Week 0 A1C. A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

    Measured: Baseline and Week 18

  12. Change From Baseline in A1C at Week 52 (Overall Cardiovascular Study)

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This change from baseline reflects the Week 52 A1C minus the Week 0 A1C. A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Baseline and Week 52

  13. Change From Baseline in A1C at Month 24 (Overall Cardiovascular Study)

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This change from baseline reflects the Month 24 A1C minus the Week 0 A1C. A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Baseline and Month 24

  14. Change From Baseline in A1C at Month 36 (Overall Cardiovascular Study)

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This change from baseline reflects the Month 36 A1C minus the Week 0 A1C. A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Baseline and Month 36

  15. Change From Baseline in A1C at Month 48 (Overall Cardiovascular Study)

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This change from baseline reflects the Month 48 A1C minus the Week 0 A1C. A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Baseline and Month 48

  16. Change From Baseline in A1C at Month 60 (Overall Cardiovascular Study)

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This change from baseline reflects the Month 60 A1C minus the Week 0 A1C. A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Baseline and Month 60

  17. Change From Baseline in A1C at Month 72 (Overall Cardiovascular Study)

    A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This change from baseline reflects the Month 72 A1C minus the Week 0 A1C. A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Baseline and Month 72

  18. Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Week 18 (Overall Cardiovascular Study)

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Week 18

  19. Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Week 52 (Overall Cardiovascular Study)

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Week 52

  20. Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Month 24 (Overall Cardiovascular Study)

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Month 24

  21. Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Month 36 (Overall Cardiovascular Study)

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Month 36

  22. Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Month 48 (Overall Cardiovascular Study)

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Month 48

  23. Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Month 60 (Overall Cardiovascular Study)

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Month 60

  24. Percentage of Participants With an A1C <6.5% (<48 mmol/Mol) at Week 18 (Overall Cardiovascular Study)

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Week 18

  25. Percentage of Participants With an A1C <6.5% (<48 mmol/Mol) at Week 52 (Overall Cardiovascular Study)

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Week 52

  26. Percentage of Participants With an A1C <6.5% (<48 mmol/Mol) at Month 24 (Overall Cardiovascular Study)

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Month 24

  27. Percentage of Participants With an A1C <6.5% (<48 mmol/Mol) at Month 36 (Overall Cardiovascular Study)

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Month 36

  28. Percentage of Participants With an A1C <6.5% (<48 mmol/Mol) at Month 48 (Overall Cardiovascular Study)

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Month 48

  29. Percentage of Participants With an A1C <6.5% (<48 mmol/Mol) at Month 60 (Overall Cardiovascular Study)

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Month 60

  30. Change From Baseline in Fasting Plasma Glucose (FPG) at Week 18 (Excluding Rescue Approach) (Overall Cardiovascular Study)

    FPG was analyzed after an overnight fast. This change from baseline reflects the Week 18 FPG minus the Week 0 FPG. A negative number indicates a reduction in FPG. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding rescue", excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

    Measured: Baseline and Week 18

  31. Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52 (Overall Cardiovascular Study)

    FPG was analyzed after an overnight fast. This change from baseline reflects the Week 52 FPG minus the Week 0 FPG. A negative number indicates a reduction in FPG. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Baseline and Week 52

  32. Change From Baseline in Fasting Plasma Glucose (FPG) at Month 24 (Overall Cardiovascular Study)

    FPG was analyzed after an overnight fast. This change from baseline reflects the Month 24 FPG minus the Week 0 FPG. A negative number indicates a reduction in FPG. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Baseline and Month 24

  33. Change From Baseline in Fasting Plasma Glucose (FPG) at Month 36 (Overall Cardiovascular Study)

    FPG was analyzed after an overnight fast. This change from baseline reflects the Month 36 FPG minus the Week 0 FPG. A negative number indicates a reduction in FPG. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Baseline and Month 36

  34. Change From Baseline in Fasting Plasma Glucose (FPG) at Month 48 (Overall Cardiovascular Study)

    FPG was analyzed after an overnight fast. This change from baseline reflects the Month 48 FPG minus the Week 0 FPG. A negative number indicates a reduction in FPG. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Baseline and Month 48

  35. Change From Baseline in Fasting Plasma Glucose (FPG) at Month 60 (Overall Cardiovascular Study)

    FPG was analyzed after an overnight fast. This change from baseline reflects the Month 60 FPG minus the Week 0 FPG. A negative number indicates a reduction in FPG. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Baseline and Month 60

  36. Change From Baseline in Fasting Plasma Glucose (FPG) at Month 72 (Overall Cardiovascular Study)

    FPG was analyzed after an overnight fast. This change from baseline reflects the Month 72 FPG minus the Week 0 FPG. A negative number indicates a reduction in FPG. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Baseline and Month 72

  37. Time to the First Occurrence of a Participant Receiving Glycemic Rescue Therapy Through Week 18 (Overall Cardiovascular Study)

    Participants who met glycemic rescue criteria received open-label sitagliptin glycemic rescue medication.

    Measured: Up to 18 weeks

  38. Time to Initiation of Insulin for Participants Not on Insulin at Baseline (Overall Cardiovascular Study)

    Participants who were not on insulin therapy at the start of study medication.

    Measured: Up to approximately 6 years

  39. Baseline Insulin Dose for Participants Who Were on Insulin at Baseline (Overall Cardiovascular Study)

    Baseline reflects Week 0 insulin dose.

    Measured: Baseline

  40. Change From Baseline in Insulin Dose at Week 18 for Participants Who Were on Insulin at Baseline (Overall Cardiovascular Study)

    This change from baseline reflects the Week 18 insulin dose minus the Week 0 insulin dose. A negative number indicates a reduction in the insulin dose.

    Measured: Baseline and Week 18

  41. Change From Baseline in Insulin Dose at Week 52 for Participants Who Were on Insulin at Baseline (Overall Cardiovascular Study)

    This change from baseline reflects the Week 52 insulin dose minus the Week 0 insulin dose. A negative number indicates a reduction in the insulin dose.

    Measured: Baseline and Week 52

  42. Change From Baseline in Insulin Dose at Month 24 for Participants Who Were on Insulin at Baseline (Overall Cardiovascular Study)

    This change from baseline reflects the Month 24 insulin dose minus the Week 0 insulin dose. A negative number indicates a reduction in the insulin dose.

    Measured: Baseline and Month 24

  43. Change From Baseline in Insulin Dose at Month 36 for Participants Who Were on Insulin at Baseline (Overall Cardiovascular Study)

    This change from baseline reflects the Month 36 insulin dose minus the Week 0 insulin dose. A negative number indicates a reduction in the insulin dose.

    Measured: Baseline and Month 36

  44. Change From Baseline in Insulin Dose at Month 48 for Participants Who Were on Insulin at Baseline (Overall Cardiovascular Study)

    This change from baseline reflects the Month 48 insulin dose minus the Week 0 insulin dose. A negative number indicates a reduction in the insulin dose.

    Measured: Baseline and Month 48

  45. Change From Baseline in Insulin Dose at Month 60 for Participants Who Were on Insulin at Baseline (Overall Cardiovascular Study)

    This change from baseline reflects the Month 60 insulin dose minus the Week 0 insulin dose. A negative number indicates a reduction in the insulin dose.

    Measured: Baseline and Month 60

  46. Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Week 18 (Excluding Rescue Approach) (Overall Cardiovascular Study)

    This change from baseline reflects the Week 18 SBP minus the Week 0 SBP. A negative number indicates a reduction in SBP. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding rescue", excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

    Measured: Baseline and Week 18

  47. Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Week 52 (Overall Cardiovascular Study)

    This change from baseline reflects the Week 52 sitting SBP minus the Week 0 SBP. A negative number indicates a reduction in SBP. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Baseline and Week 52

  48. Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Month 24 (Overall Cardiovascular Study)

    This change from baseline reflects the Month 24 SBP minus the Week 0 SBP. A negative number indicates a reduction in SBP. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Baseline and Month 24

  49. Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Month 36 (Overall Cardiovascular Study)

    This change from baseline reflects the Month 36 SBP minus the Week 0 SBP. A negative number indicates a reduction in SBP. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Baseline and Month 36

  50. Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Month 48 (Overall Cardiovascular Study)

    This change from baseline reflects the Month 48 SBP minus the Week 0 SBP. A negative number indicates a reduction in SBP. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Baseline and Month 48

  51. Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Month 60 (Overall Cardiovascular Study)

    This change from baseline reflects the Month 60 SBP minus the Week 0 SBP. A negative number indicates a reduction in SBP. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Baseline and Month 60

  52. Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Month 72 (Overall Cardiovascular Study)

    This change from baseline reflects the Month 72 SBP minus the Week 0 SBP. A negative number indicates a reduction in SBP. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Baseline and Month 72

  53. Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Week 18 (Excluding Rescue Approach) (Overall Cardiovascular Study)

    This change from baseline reflects the Week 18 DBP minus the Week 0 DBP. A negative number indicates a reduction in DBP. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding rescue", excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

    Measured: Baseline and Week 18

  54. Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Week 52 (Overall Cardiovascular Study)

    This change from baseline reflects the Week 52 DBP minus the Week 0 DBP. A negative number indicates a reduction in DBP. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Baseline and Week 52

  55. Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Month 24 (Overall Cardiovascular Study)

    This change from baseline reflects the Month 24 DBP minus the Week 0 DBP. A negative number indicates a reduction in DBP. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Baseline and Month 24

  56. Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Month 36 (Overall Cardiovascular Study)

    This change from baseline reflects the Month 36 DBP minus the Week 0 DBP. A negative number indicates a reduction in DBP. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Baseline and Month 36

  57. Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Month 48 (Overall Cardiovascular Study)

    This change from baseline reflects the Month 48 DBP minus the Week 0 DBP. A negative number indicates a reduction in DBP. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Baseline and Month 48

  58. Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Month 60 (Overall Cardiovascular Study)

    This change from baseline reflects the Month 60 DBP minus the Week 0 DBP. A negative number indicates a reduction in DBP. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Baseline and Month 60

  59. Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Month 72 (Overall Cardiovascular Study)

    This change from baseline reflects the Month 72 DBP minus the Week 0 DBP. A negative number indicates a reduction in DBP. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Baseline and Month 72

  60. Change From Baseline in Body Weight at Week 18 (Excluding Rescue Approach) (Overall Cardiovascular Study)

    This change from baseline reflects the Week 18 body weight minus the Week 0 body weight. A negative number indicates a reduction in body weight. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

    Measured: Baseline and Week 18

  61. Change From Baseline in Body Weight at Week 52 (Overall Cardiovascular Study)

    This change from baseline reflects the Week 52 body weight minus the Week 0 body weight. A negative number indicates a reduction in body weight. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Baseline and Week 52

  62. Change From Baseline in Body Weight at Month 24 (Overall Cardiovascular Study)

    This change from baseline reflects the Month 24 body weight minus the Week 0 body weight. A negative number indicates a reduction in body weight. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Baseline and Month 24

  63. Change From Baseline in Body Weight at Month 36 (Overall Cardiovascular Study)

    This change from baseline reflects the Month 36 body weight minus the Week 0 body weight. A negative number indicates a reduction in body weight. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Baseline and Month 36

  64. Change From Baseline in Body Weight at Month 48 (Overall Cardiovascular Study)

    This change from baseline reflects the Month 48 body weight minus the Week 0 body weight. A negative number indicates a reduction in body weight. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Baseline and Month 48

  65. Change From Baseline in Body Weight at Month 60 (Overall Cardiovascular Study)

    This change from baseline reflects the Month 60 body weight minus the Week 0 body weight. A negative number indicates a reduction in body weight. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Baseline and Month 60

  66. Change From Baseline in Body Weight at Month 72 (Overall Cardiovascular Study)

    This change from baseline reflects the Month 72 body weight minus the Week 0 body weight. A negative number indicates a reduction in body weight. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Baseline and Month 72

  67. Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 18 (Overall Cardiovascular Study)

    This change from baseline reflects the Week 18 eGFR minus the Week 0 eGFR. A negative number indicates a reduction in the eGFR level.

    Measured: Baseline and Week 18

  68. Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 52 (Overall Cardiovascular Study)

    This change from baseline reflects the Week 52 eGFR minus the Week 0 eGFR. A negative number indicates a reduction in eGFR level.

    Measured: Baseline and Week 52

  69. Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Month 24 (Overall Cardiovascular Study)

    This change from baseline reflects the Month 24 eGFR minus the Week 0 eGFR. A negative number indicates a reduction in the eGFR level.

    Measured: Baseline and Month 24

  70. Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Month 36 (Overall Cardiovascular Study)

    This change from baseline reflects the Month 36 eGFR minus the Week 0 eGFR. A negative number indicates a reduction in the eGFR level.

    Measured: Baseline and Month 36

  71. Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Month 48 (Overall Cardiovascular Study)

    This change from baseline reflects the Month 48 eGFR minus the Week 0 eGFR. A negative number indicates a reduction in eGFR level.

    Measured: Baseline and Month 48

  72. Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Month 60 (Overall Cardiovascular Study)

    This change from baseline reflects the Month 60 eGFR minus the Week 0 eGFR. A negative number indicates a reduction in the eGFR level.

    Measured: Baseline and Month 60

  73. Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Month 72 (Overall Cardiovascular Study)

    This change from baseline reflects the Month 72 eGFR minus the Week 0 eGFR. A negative number indicates a reduction in the eGFR level.

    Measured: Baseline and Month 72

  74. Baseline Serum Creatinine (Overall Cardiovascular Study)

    Baseline reflects Week 0 serum creatinine.

    Measured: Baseline

  75. Change From Baseline in Serum Creatinine at Week 18 (Overall Cardiovascular Study)

    This change from baseline reflects the Week 18 serum creatinine minus the Week 0 serum creatinine. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Baseline and Week 18

  76. Change From Baseline in Serum Creatinine at Week 52 (Overall Cardiovascular Study)

    This change from baseline reflects the Week 52 serum creatinine minus the Week 0 serum creatinine. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Baseline and Week 52

  77. Change From Baseline in Serum Creatinine at Month 24 (Overall Cardiovascular Study)

    This change from baseline reflects the Month 24 serum creatinine minus the Week 0 serum creatinine. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Baseline and Month 24

  78. Change From Baseline in Serum Creatinine at Month 36 (Overall Cardiovascular Study)

    This change from baseline reflects the Month 36 serum creatinine minus the Week 0 serum creatinine. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Baseline and Month 36

  79. Change From Baseline in Serum Creatinine at Month 48 (Overall Cardiovascular Study)

    This change from baseline reflects the Month 48 serum creatinine minus the Week 0 serum creatinine. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Baseline and Month 48

  80. Change From Baseline in Serum Creatinine at Month 60 (Overall Cardiovascular Study)

    This change from baseline reflects the Month 60 serum creatinine minus the Week 0 serum creatinine. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Baseline and Month 60

  81. Change From Baseline in Serum Creatinine at Month 72 (Overall Cardiovascular Study)

    This change from baseline reflects the Month 72 serum creatinine minus the Week 0 serum creatinine. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Baseline and Month 72

  82. Baseline Urinary Albumin/Creatinine Ratio (Overall Cardiovascular Study)

    Baseline reflects Week 0 albumin/creatinine ratio.

    Measured: Baseline

  83. Percent Change From Baseline in Urinary Albumin/Creatinine Ratio at Week 18 (Overall Cardiovascular Study)

    This percent change relative to baseline reflects the Week 18 albumin/creatinine ratio minus the Week 0 albumin/creatinine ratio. This difference was divided by the baseline to obtain the percent change. A negative number indicates a reduction in the urinary albumin/creatinine ratio. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Baseline and Week 18

  84. Percent Change From Baseline in Urinary Albumin/Creatinine Ratio at Week 52 (Overall Cardiovascular Study)

    This percent change relative to baseline reflects the Week 52 albumin/creatinine ratio minus the Week 0 albumin/creatinine ratio. This difference was divided by the baseline to obtain the percent change. A negative number indicates a reduction in the albumin/creatinine ratio. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Baseline and Week 52

  85. Percent Change From Baseline in Urinary Albumin/Creatinine Ratio at Month 24 (Overall Cardiovascular Study)

    This percent change relative to baseline reflects the Month 24 albumin/creatinine ratio minus the Week 0 albumin/creatinine ratio. This difference was divided by the baseline to obtain the percent change. A negative number indicates a reduction in urinary albumin/creatinine ratio. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Baseline and Month 24

  86. Percent Change From Baseline in Urinary Albumin/Creatinine Ratio at Month 36 (Overall Cardiovascular Study)

    This percent change relative to baseline reflects the Month 36 albumin/creatinine ratio minus the Week 0 albumin/creatinine ratio. This difference was divided by the baseline to obtain the percent change. A negative number indicates a reduction in urinary albumin/creatinine ratio. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Baseline and Month 36

  87. Percent Change From Baseline in Urinary Albumin/Creatinine Ratio at Month 48 (Overall Cardiovascular Study)

    This percent change relative to baseline reflects the Month 48 albumin/creatinine ratio minus the Week 0 albumin/creatinine ratio. This difference was divided by the baseline to obtain the percent change. A negative number indicates a reduction in albumin/creatinine ratio. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Baseline and Month 48

  88. Percent Change From Baseline in Urinary Albumin/Creatinine Ratio at Month 60 (Overall Cardiovascular Study)

    This percent change relative to baseline reflects the Month 60 albumin/creatinine ratio minus the Week 0 albumin/creatinine ratio. This difference was divided by the baseline to obtain the percent change. A negative number indicates a reduction in albumin/creatinine ratio. Participants who met glycemic rescue criteria received glycemic rescue medication.

    Measured: Baseline and Month 60

  89. Percentage of Participants With Albuminuria Progression or Regression at Week 18 (Overall Cardiovascular Study)

    Albuminuria progression and regression were assessed relative to the baseline albuminuria category. Progression was defined as either a change from having normal-albuminuria at baseline to micro-albuminuria at the respective visit, or micro-albuminuria at baseline to macro-albuminuria at the respective visit, or normal albuminuria at baseline to macro-albuminuria at the respective visit. Regression was defined as either a change from having micro-albuminuria at baseline to normal albuminuria at the respective visit, or macro-albuminuria at baseline to micro-albuminuria at the respective visit, or macro-albuminuria at baseline to normal albuminuria at the respective visit. Normal albuminuria: urine albumin to urinary creatinine ratio (UACR) <30 (mg/g); Micro-albuminuria: UACR ≥30 and ≤300 (mg/g); Macro-albuminuria: UACR>300 (mg/g).

    Measured: Week 18

  90. Percentage of Participants With Albuminuria Progression or Regression at Week 52 (Overall Cardiovascular Study)

    Albuminuria progression and regression were assessed relative to the baseline albuminuria category. Progression was defined as either a change from having normal albuminuria at baseline to micro-albuminuria at the respective visit, or micro-albuminuria at baseline to macro-albuminuria at the respective visit, or normal albuminuria at baseline to macro-albuminuria at the respective visit. Regression was defined as either a change from having micro-albuminuria at baseline to normal albuminuria at the respective visit, or macro-albuminuria at baseline to micro-albuminuria at the respective visit, or macro-albuminuria at baseline to normal albuminuria at the respective visit. Normal albuminuria: urine albumin to urinary creatinine ratio (UACR) <30 (mg/g); Micro-albuminuria: UACR ≥30 and ≤300 (mg/g); Macro-albuminuria: UACR>300 (mg/g).

    Measured: Week 52

  91. Percentage of Participants With Albuminuria Progression or Regression at Month 24 (Overall Cardiovascular Study)

    Albuminuria progression and regression were assessed relative to the baseline albuminuria category. Progression was defined as either a change from having normal albuminuria at baseline to micro-albuminuria at the respective visit, or micro-albuminuria at baseline to macro-albuminuria at the respective visit, or normal albuminuria at baseline to macro-albuminuria at the respective visit. Regression was defined as either a change from having micro-albuminuria at baseline to normal albuminuria at the respective visit, or macro-albuminuria at baseline to micro-albuminuria at the respective visit, or macro-albuminuria at baseline to normal albuminuria at the respective visit. Normal albuminuria: urine albumin to urinary creatinine ratio (UACR) <30 (mg/g); Micro-albuminuria: UACR ≥30 and ≤300 (mg/g); Macro-albuminuria: UACR>300 (mg/g).

    Measured: Month 24

  92. Percentage of Participants With Albuminuria Progression or Regression at Month 36 (Overall Cardiovascular Study)

    Albuminuria progression and regression were assessed relative to the baseline albuminuria category. Progression was defined as either a change from having normal albuminuria at baseline to micro-albuminuria at the respective visit, or micro-albuminuria at baseline to macro-albuminuria at the respective visit, or normal albuminuria at baseline to macro-albuminuria at the respective visit. Regression was defined as either a change from having micro-albuminuria at baseline to normal albuminuria at the respective visit, or macro-albuminuria at baseline to micro-albuminuria at the respective visit, or macro-albuminuria at baseline to normal albuminuria at the respective visit. Normal albuminuria: urine albumin to urinary creatinine ratio (UACR) <30 (mg/g); Micro-albuminuria: UACR ≥30 and ≤300 (mg/g); Macro-albuminuria: UACR>300 (mg/g).

    Measured: Month 36

  93. Percentage of Participants With Albuminuria Progression or Regression at Month 48 (Overall Cardiovascular Study)

    Albuminuria progression and regression were assessed relative to the baseline albuminuria category. Progression was defined as either a change from having normal albuminuria at baseline to micro-albuminuria at the respective visit, or micro-albuminuria at baseline to macro-albuminuria at the respective visit, or normal albuminuria at baseline to macro-albuminuria at the respective visit. Regression was defined as either a change from having micro-albuminuria at baseline to normal albuminuria at the respective visit, or macro-albuminuria at baseline to micro-albuminuria at the respective visit, or macro-albuminuria at baseline and normal albuminuria at the respective visit. Normal albuminuria: urine albumin to urinary creatinine ratio (UACR) <30 (mg/g); Micro-albuminuria: UACR ≥30 and ≤300 (mg/g); Macro-albuminuria: UACR>300 (mg/g).

    Measured: Month 48

  94. Percentage of Participants With Albuminuria Progression or Regression at Month 60 (Overall Cardiovascular Study)

    Albuminuria progression and regression were assessed relative to the baseline albuminuria category. Progression was defined as either a change from having normal albuminuria at baseline to micro albuminuria at the respective visit, or micro-albuminuria at baseline to macro-albuminuria at the respective visit, or normal albuminuria at baseline to macro-albuminuria at the respective visit. Regression was defined as either a change from having micro-albuminuria at baseline to normal albuminuria at the respective visit, or macro-albuminuria at baseline to micro-albuminuria at the respective visit, or macro-albuminuria at baseline to normal albuminuria at the respective visit. Normal albuminuria: urine albumin to urinary creatinine ratio (UACR) <30 (mg/g); Micro-albuminuria: UACR ≥30 and ≤300 (mg/g); Macro-albuminuria: UACR>300 (mg/g).

    Measured: Month 60

  95. Percentage of Participants Experiencing an Adverse Event (AE) (Overall Cardiovascular Study)

    An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

    Measured: Up to approximately 6 years

  96. Percentage of Participants Experiencing an Adverse Event (AE) (Insulin With or Without Metformin Add-on Glycemic Sub-study)

    An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

    Measured: Up to 18 weeks

  97. Percentage of Participants Experiencing an Adverse Event (AE) (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)

    An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

    Measured: Up to 18 weeks

  98. Percentage of Participants Experiencing an Adverse Event (AE) (Metformin With Sulfonylurea Add-on Glycemic Sub-study)

    An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

    Measured: Up to 18 weeks

  99. Percentage of Participants Discontinuing Study Treatment Due to An AE (Overall Cardiovascular Study)

    An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

    Measured: Up to approximately 6 years

  100. Percentage of Participants Discontinuing Study Treatment Due to An AE (Insulin With or Without Metformin Add-on Glycemic Sub-study)

    An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

    Measured: Up to 18 weeks

  101. Percentage of Participants Discontinuing Study Treatment Due to An AE (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)

    An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

    Measured: Up to 18 weeks

  102. Percentage of Participants Discontinuing Study Treatment Due to An AE (Metformin With Sulfonylurea Add-on Glycemic Sub-study)

    An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

    Measured: Up to 18 weeks

  103. Change From Baseline in Fasting Plasma Glucose (FPG) at Week 18 (Excluding Rescue Approach) (Insulin With or Without Metformin Add-on Glycemic Sub-study)

    FPG was analyzed after an overnight fast. This change from baseline reflects the Week 18 FPG minus the Week 0 FPG. A negative number indicates a reduction in the FPG. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

    Measured: Baseline and Week 18

  104. Change From Baseline in Body Weight at Week 18 (Excluding Rescue Approach) (Insulin With or Without Metformin Add-on Glycemic Sub-study)

    This change from baseline reflects the Week 18 body weight minus the Week 0 body weight. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

    Measured: Baseline and Week 18

  105. Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Week 18 (Excluding Rescue Approach) (Insulin With or Without Metformin Add-on Glycemic Sub-study)

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

    Measured: Week 18

  106. Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Week 18 (Excluding Rescue Approach) (Insulin With or Without Metformin Add-on Glycemic Sub-study)

    This change from baseline reflects the Week 18 SBP minus the Week 0 SBP. A negative number indicates a reduction in SBP. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

    Measured: Baseline and Week 18

  107. Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Week 18 (Excluding Rescue Approach) (Insulin With or Without Metformin Add-on Glycemic Sub-study)

    This change from baseline reflects the Week 18 DBP minus the Week 0 BBP. A negative number indicates a reduction in DBP. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

    Measured: Baseline and Week 18

  108. Baseline Insulin Dose for Participants Receiving Insulin at Baseline - (Insulin With or Without Metformin Add-on Glycemic Sub-study)

    Baseline reflects Week 0 insulin dose.

    Measured: Baseline

  109. Change From Baseline at Week 18 in Insulin Dose for Participants Receiving Insulin at Baseline - Including Rescue Approach (Insulin With or Without Metformin Add-on Glycemic Sub-study)

    This change from baseline reflects the Week 18 insulin dose minus the Week 0 insulin dose. A negative number indicates a decrease in insulin dose. Participants who met glycemic rescue criteria received glycemic rescue medication. "Including rescue", included data following the initiation of rescue therapy.

    Measured: Baseline and Week 18

  110. Change From Baseline in Fasting Plasma Glucose (FPG) at Week 18 (Excluding Rescue Approach) (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)

    FPG was analyzed after an overnight fast. This change from baseline reflects the Week 18 FPG minus the Week 0 FPG. A negative number indicates a reduction in FPG. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

    Measured: Baseline and Week 18

  111. Change From Baseline in Body Weight at Week 18 (Excluding Rescue Approach) (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)

    This change from baseline reflects the Week 18 body weight minus the Week 0 body weight. A negative number indicates a reduction in body weight. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

    Measured: Baseline and Week 18

  112. Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Week 18 (Excluding Rescue Approach) (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

    Measured: Week 18

  113. Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Week 18 (Excluding Rescue Approach) (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)

    This change from baseline reflects the Week 18 SBP minus the Week 0 SBP. A negative number indicates a reduction in SBP. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

    Measured: Baseline and Week 18

  114. Change From Baseline in Sitting Diastolic Blood (DBP) Pressure at Week 18 (Excluding Rescue Approach) (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)

    This change from baseline reflects the Week 18 DBP minus the Week 0 DBP. A negative number indicates a reduction in DBP. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

    Measured: Baseline and Week 18

  115. Change From Baseline in Fasting Plasma Glucose (FPG) at Week 18 (Excluding Rescue Approach) (Metformin With Sulfonylurea Add-on Glycemic Sub-study)

    FPG was analyzed after an overnight fast. This change from baseline reflects the Week 18 FPG minus the Week 0 FPG. A negative number indicates a reduction in FPG. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

    Measured: Baseline and Week 18

  116. Change From Baseline in Body Weight at Week 18 (Excluding Rescue Approach) (Metformin With Sulfonylurea Add-on Glycemic Sub-study)

    This change from baseline reflects the Week 18 body weight minus the Week 0 body weight. A negative number indicates a reduction in body weight. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

    Measured: Baseline and Week 18

  117. Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Week 18 (Excluding Rescue Approach) (Metformin With Sulfonylurea Add-on Glycemic Sub-study)

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

    Measured: Week 18

  118. Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Week 18 (Excluding Rescue Approach) (Metformin With Sulfonylurea Add-on Glycemic Sub-study)

    This change from baseline reflects the Week 18 SBP minus the Week 0 SBP. A negative number indicates a reduction in SBP. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

    Measured: Baseline and Week 18

  119. Change From Baseline in Sitting Diastolic Blood (DBP) Pressure at Week 18 (Excluding Rescue Approach) (Metformin With Sulfonylurea Add-on Glycemic Sub-study)

    This change from baseline reflects the Week 18 DBP minus the Week 0 DBP. A negative number indicates a reduction in DBP. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

    Measured: Baseline and Week 18

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Nov 2013 (estimated)
  2. Study start4 Nov 2013
  3. Primary completion27 Dec 2019
  4. Study completion27 Dec 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
8,246 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01986881
Sponsor's protocol ID
8835-004
Other IDs
2013-002518-11, B1521021
Status last verified
Sep 2022
First submitted
12 Nov 2013
Last updated
23 Sep 2022
Data monitoring committee
Yes
Individual data sharing
Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

  • Cannon CP, McGuire DK, Pratley R, Dagogo-Jack S, Mancuso J, Huyck S, Charbonnel B, Shih WJ, Gallo S, Masiukiewicz U, Golm G, Cosentino F, Lauring B, Terra SG; VERTIS-CV Investigators. Design and baseline characteristics of the eValuation of ERTugliflozin effIcacy and Safety CardioVascular outcomes trial (VERTIS-CV). Am Heart J. 2018 Dec;206:11-23. doi: 10.1016/j.ahj.2018.08.016. Epub 2018 Sep 5.

    PubMed 30290289

  • Natale P, Tunnicliffe DJ, Toyama T, Palmer SC, Saglimbene VM, Ruospo M, Gargano L, Stallone G, Gesualdo L, Strippoli GF. Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev. 2024 May 21;5(5):CD015588. doi: 10.1002/14651858.CD015588.pub2.

    PubMed 38770818

  • Pratley RE, Cannon CP, Cherney DZI, Cosentino F, McGuire DK, Essex MN, Lawrence D, Jones PLS, Liu J, Adamsons I, Dagogo-Jack S. Cardiorenal outcomes, kidney function, and other safety outcomes with ertugliflozin in older adults with type 2 diabetes (VERTIS CV): secondary analyses from a randomised, double-blind trial. Lancet Healthy Longev. 2023 Apr;4(4):e143-e154. doi: 10.1016/S2666-7568(23)00032-6.

    PubMed 37003273

  • Cherney DZI, Cosentino F, Dagogo-Jack S, McGuire DK, Pratley RE, Frederich R, Maldonado M, Liu CC, Pong A, Cannon CP; VERTIS CV Investigators. Initial eGFR Changes with Ertugliflozin and Associations with Clinical Parameters: Analyses from the VERTIS CV Trial. Am J Nephrol. 2022;53(7):516-525. doi: 10.1159/000524889. Epub 2022 Jun 10.

    PubMed 35691283

  • Segar MW, Kolkailah AA, Frederich R, Pong A, Cannon CP, Cosentino F, Dagogo-Jack S, McGuire DK, Pratley RE, Liu CC, Maldonado M, Liu J, Cater NB, Pandey A, Cherney DZI. Mediators of ertugliflozin effects on heart failure and kidney outcomes among patients with type 2 diabetes mellitus. Diabetes Obes Metab. 2022 Sep;24(9):1829-1839. doi: 10.1111/dom.14769. Epub 2022 Jun 15.

    PubMed 35603908

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Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ertugliflozin and Glycemic Rescue in people with Type 2 Diabetes Mellitus, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Feb 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time to First Occurrence of MACE (Composite Endpoint of Major Adverse Cardiovascular Events [Cardiovascular Death, Non-fatal Myocardial Infarction or Non-fatal Stroke]) (On-Treatment + 365-day Approach) (Overall Cardiovascular Study) (time frame: Up to approximately 6 years). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01986881, which also lists 17 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2022.

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