In recent years, clinical studies have transformed the way we manage type 2 diabetes, shifting the focus beyond just blood sugar control to protecting your heart and kidneys as well.
New research studies have shaped how type 2 diabetes is treated compared to even 10 years ago. Looking back, in 2008, the U.S. Federal Drug Administration mandated that all new medications used to treat type 2 diabetes be tested to ensure that they do not cause more cardiovascular harm than the standard treatment. Initially, studies were able to show that many new medications caused no increased risk to the heart. More recently, studies have shown that these treatments can actually help the heart and kidneys, which has led to changes in how they’re used in practice.
How are these clinical studies set up?
All safety studies are large, randomised trials with two groups of participants: one group receiving usual care and the second group receiving usual care, plus a new medication.
Participants in both groups have a history of heart or kidney disease, or are considered to be at high risk for these conditions. In studies where all participants have diabetes, both groups have the same A1C target during the trials. After a period of time (about 3-4 years), the number of outcome events (cardiovascular or kidney disease events) are compared between the two groups.
The following chart highlights the key studies that have changed practice in managing type 2 diabetes.
| Study Name | Population Studied |
Medication Studied |
Medication Category |
Study Results (MACE = Major adverse cardiovascular events) |
|---|---|---|---|---|
| CARDIOVASCULAR | ||||
| The Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients—Removing Excess Glucose (EMPA-REG OUTCOME) |
Type 2 diabetes patients with established cardiovascular disease (CVD) | Empagliflozin (Jardiance®) | SGLT2 Inhibitor | A reduction in MACE, death, heart failure and nephropathy |
| The Canagliflozin Cardiovascular Assessment Study (CANVAS and CANVAS-R) |
Type 2 diabetes patients with or at high risk for CVD | Canagliflozin (Invokana®) | SGLT2 Inhibitor | A reduction in MACE, heart failure and nephropathy |
| The Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) |
Type 2 diabetes patients with or at high risk for CVD | Liraglutide (Victoza®) | GLP-1 receptor agonist (daily) | A reduction in MACE, death and nephropathy |
| The Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes (SUSTAIN-6) |
Type 2 diabetes patients with or at high risk for CVD | Semaglutide injected (Ozempic®) | GLP-1 receptor agonist (weekly) | A reduction in MACE and nephropathy |
| Dapagliflozin Effect on Cardiovascular Events—Thrombolysis in Myocardial Infarction 58 (DECLARE-TIMI 58) |
Type 2 diabetes patients with or at high risk for CVD | Dapagliflozin (Farxiga®) | SGLT2 Inhibitor | A reduction in heart failure hospitalization and progression of renal disease; no significant reduction in MACE |
| Researching Cardiovascular Events with a Weekly Incretin in Diabetes (REWIND) |
Type 2 diabetes patients with or at high risk for CVD | Dulaglutide (Trulicity®) | GLP-1 Receptor Agonist (weekly) | A reduction in MACE; no significant reduction in mortality |
| Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity (SOUL) |
Type 2 diabetes patients with established CVD or kidney disease | Semaglutide oral (Rybelsus®) | GLP-1 Receptor Agonist (daily) | A reduction in MACE; no reduction in major kidney disease events |
| Cardiovascular Outcomes Trial of Tirzepatide in Participants With Type 2 Diabetes (SURPASS-CVOT) |
Type 2 diabetes patients with established CVD | Tirzepatide (Mounjaro®) | GLP-1/GIP co-agonist (weekly) | Ongoing (results pending; study designed to assess MACE) |
| KIDNEY | ||||
| Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) |
Type 2 diabetes patients with chronic kidney disease | Canagliflozin (Invokana®) | SGLT2 Inhibitor | A reduction in kidney failure, cardiovascular or renal death, MI or stroke, and hospitalization for heart failure |
| Empagliflozin in Patients with Chronic Kidney Disease (EMPA-KIDNEY) |
Patients with chronic kidney disease (with or without type 2 diabetes) | Empagliflozin (Jardiance®) | SGLT2 Inhibitor | A reduction in progression of kidney disease and cardiovascular death |
| Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) |
Patients with chronic kidney disease (with or without type 2 diabetes) | Dapagliflozin (Farxiga®) | SGLT2 Inhibitor | A reduction in progression of kidney disease, cardiovascular or renal death, and hospitalization for heart failure |
| Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease (FIDELITY) |
Patients with chronic kidney disease and type 2 diabetes | Finerenone (Kerendia®) | Nonsteroidal mineralocorticoid receptor antagonist | A reduction in kidney and cardiovascular outcomes (cardiovascular death, MI, stroke, hospitalization for heart failure, kidney failure, kidney disease progression) |
| Semaglutide’s Effects on Kidney Outcomes in People With Type 2 Diabetes and Chronic Kidney Disease (FLOW) |
Type 2 diabetes patients with chronic kidney disease | Semaglutide (Ozempic®) | GLP-1 Receptor Agonist (weekly) | A reduction in kidney failure, progression of kidney disease, and cardiovascular and renal death |
How have these studies impacted care?
While the primary focus in type 2 diabetes care used to be on lowering blood glucose levels, as a result of the above trials, the focus has shifted toward protection of the heart and the kidneys. While metformin is still recommended as the initial medication of choice for lowering blood sugars, additional medications should prioritize protection of the heart and kidneys for those who already have cardiovascular or kidney disease or have multiple risk factors for these conditions. Therefore, SGLT2 inhibitors or GLP-1 receptor agonists are often recommended, even if blood sugars are already at the target level. In patients with type 2 diabetes and chronic kidney disease, finerenone is recommended for cardiovascular and renal benefit, even though it does not affect blood sugars.
How has insulin treatment changed?
Two second-generation long-acting insulins (basal insulins) have been compared to first-generation basal insulins (glargine [Lantus®] and detemir [Levermir®]) in several randomized clinical trials. These second-generation basal insulins are insulin glargine U300 (Toujeo®) and insulin degludec (Tresiba®). Across all of these trials, second-generation basal insulins were shown to achieve similar glucose levels as the first-generation basal insulins, but with lower rates of hypoglycemia. Most recently, third generation basal insulins have become available (e.g., insulin icodec [Awiqli®]), which only need to be administered once per week. When studied in randomized trials, weekly insulin icodec achieved comparable blood sugar control to daily basal insulin, while requiring fewer injections and offering greater treatment satisfaction.
How have continuous glucose monitors (CGM) affected diabetes management?
Many randomized controlled trials have compared blood glucose monitoring using capillary glucose meters (fingerpricks) to continuous glucose monitors (CGM) . In individuals with type 2 diabetes using insulin, CGM lowers hemoglobin A1C, increases the time spent in the target glucose range (3.9-10mmol/L) and reduces hypoglycemia. In individuals not using insulin, CGM increases time spent in the target glucose range and reduces hemoglobin A1C.
Recent advancements have redefined type 2 diabetes care to a more holistic approach that supports overall health. Thanks to this research, newer medications like SGLT2 inhibitors and GLP-1 receptor agonists now offer added cardiovascular and renal benefits. Advances in insulin formulations provide more flexibility and fewer side effects, while CGMs are making it easier than ever to track and manage glucose levels in real time. These innovations are helping people with type 2 diabetes live longer, healthier lives with greater confidence and control.
