Table 3.
Ongoing clinical trials of anti-hyperglycemic medications evaluating cardiovascular safety and efficacy
| Trial Comparing Cardiovascular Safety of Insulin Degludec Versus Insulin Glargine in Subjects With Type 2 Diabetes at High Risk of Cardiovascular Events (DEVOTE) (NCT01959529) |
The Sitagliptin Cardiovascular Outcome Study (TECOS) (NCT00790205) |
The Cardiovascular Outcome Study of Linagliptin versus Glimepiride in Patients with Type 2 Diabetes (CAROLINA) (NCT01243424) |
The Cardiovascular and Renal Microvascular Outcome Study With Linagliptin in Patients With Type 2 Diabetes Mellitus (CARMELINA) (NCT01897532) |
The Exenatide Study of Cardiovascular Event Lowering Trial (EXSCEL) (NCT01144338) |
The Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results - A Long Term Evaluation (LEADER) (NCT01179048) |
|
| Drug Assessed | Insulin degludec | Sitagliptin | Linagliptin | Linagliptin | Exenatide once weekly |
Liraglutide |
| Comparator | Insulin glargine | Placebo | Glimepiride | Placebo | Placebo | Placebo |
| Estimated Enrollment |
N=7,644 | N=14,724 | N=6,000 | N=8,300 | N=14,000 | N=9,340 |
| Primary Outcome | Composite: CV death, non-fatal MI, or non-fatal stroke |
composite endpoint: time to first confirmed CV-related death, nonfatal MI, or non-fatal ischemic stroke |
composite endpoint: CV death, non-fatal MI (excluding silent MI), non-fatal stroke and hospitalization for unstable angina pectoris |
composite endpoint: CV death, non-fatal MI, non-fatal stroke and hospitalization for unstable angina pectoris |
Composite: CV death, nonfatal MI, or nonfatal stroke |
Composite: CV death, non-fatal MI, or non-fatal stroke |
| Follow up | 5 years | 3 years | 7.7 years | 4 years | 7.5 years | 5 years |
| Anticipated completion |
2018 | June 2015 | September 2018 | January 2018 | April 2018 | October 2015 |
| Researching Cardiovascular Events With a Weekly Incretin in Diabetes (REWIND) (NCT01394952) |
Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes (SUSTAIN 6) (NCT01720446) |
Empagliflozin) Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) (NCT01131676) |
CANagliflozin cardioVascular Assessment Study (CANVAS) (NCT01032629) |
Multicenter Trial to Evaluate the Effect of Dapagliflozin on the Incidence of Cardiovascular Events (DECLARE- TIMI 58) (NCT01730534) |
Cardiovascular Outcomes Following Treatment With Ertugliflozin in Participants With Type 2 Diabetes Mellitus and Established Vascular Disease (VERTIS) (NCT01986881) |
|
| Drug Assessed | Dulaglutide | Semaglutide | Empagliflozin | Canagliflozin | Dapagliflozin | Ertugliflozin |
| Comparator | Placebo | Placebo | Placebo | Placebo | Placebo | Placebo |
| Estimated Enrollment |
N=9,622 | N=3,297 | N=7,000 | N=14,000 | N=17,150 | N=3,900 |
| Primary Outcome | Composite: CV death, non-fatal MI, or non-fatal stroke |
Composite: CV death, non-fatal MI, or non-fatal stroke |
Composite: CV death (including fatal stroke and fatal MI), non- fatal MI (excluding silent MI) and non- fatal stroke |
Composite: CV death, non-fatal MI, non-fatal stroke |
Composite: CV death, MI or ischemic stroke |
Composite: CV Death, Non-fatal MI, or Non-fatal Stroke |
| Follow up | 6.5 years | 2.8 years | 5 years | 7.5 years | 6 years | 6.3 years |
| Anticipated completion |
April 2019 | 2016 | April 2015 | June 2018 | April 2019 | May 2021 |
| Thiazolidinediones Or Sulphonylureas and Cardiovascular Accidents.Intervention Trial (TOSCA IT) (NCT00700856) |
Acarbose Cardiovascular Evaluation Trial (ACE) (NCT00829660) |
Evaluation of Cardiovascular Outcomes in Patients With Type 2 Diabetes After Acute Coronary Syndrome During Treatment With AVE0010 (Lixisenatide) (ELIXA) (NCT01147250) |
A Trial Comparing Cardiovascular Safety of Insulin Degludec Versus Insulin Glargine in Subjects With Type 2 Diabetes at High Risk of Cardiovascular Events (DEVOTE) (NCT01959529) |
A Study of the Effects of Canagliflozin (JNJ- 28431754) on Renal Endpoints in Adult Participants With Type 2 Diabetes Mellitus (CANVAS-R) (NCT01989754) |
Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy (CREDENCE) (NCT02065791) |
|
| Drug Assessed | Pioglitazone | Acarbose | Lixisenatide | Insulin degludec | Canagliflozin | Canagliflozin |
| Comparator | Glibenclamide, gliclazide, or glimepiride |
Placebo | Placebo | Insulin glargine | Placebo | Placebo |
| Estimated Enrollment |
3,371 | 7,500 | 6,075 | 7,644 | 5,700 | 3,700 |
| Primary Outcome | Composite: all-cause mortality, non-fatal MI ( including silent MI), non-fatal stroke, unplanned coronary revascularization |
Composite: Cardiovascular death, Non-fatal MI, Non-fatal stroke |
Composite: CV death, non-fatal MI, non-fatal stroke, hospitalization for unstable angina |
Composite: cardiovascular death, non-fatal MI, or non- fatal stroke |
Progression of albuminuria Secondary outcome: Composite: CV death, nonfatal MI, and nonfatal stroke |
Composite: ESKD, doubling of serum creatinine, renal or CV death |
| Follow up | 4 years | 4 years | 3.9 years | 5 years | 3 years | 5.5 years |
| Anticipated completion |
December 2018 | October 2014 | February 2015 | November 2018 | April 2017 | January 2020 |
Legend: CV=cardiovascular, MI=myocardial infarction, ESKD=End stage kidney disease