Diabetes Trial Files Throwback Thursday: Canagliflozin for T2DM, Intensive vs. Standard Glucose Lowering Therapy, and Renoprotective Effect of Irbesartan
Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes
Neal B et al. NEJM (August 2017)
Bottom Line: The CANVAS Program, a study involving 10,142 participants with type 2 diabetes and high cardiovascular risk, evaluated the effects of canagliflozin, a sodium-glucose cotransporter 2 inhibitor, on cardiovascular, renal, and safety outcomes. Participants were randomly assigned to receive canagliflozin or placebo and were followed for a mean of 188.2 weeks. The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Canagliflozin showed a lower risk of the primary outcome compared to placebo (hazard ratio, 0.86; 95% CI, 0.75 to 0.97; P<0.001 for noninferiority; P=0.02 for superiority). However, there was a higher risk of amputation, primarily at the level of the toe or metatarsal, in the canagliflozin group. The study did not find statistically significant results for renal outcomes, but there was a possible benefit of canagliflozin in terms of albuminuria and a composite outcome of renal function decline, need for renal-replacement therapy, or death from renal causes. Adverse reactions were consistent with previously reported risks, except for an increased risk of amputation. In conclusion, canagliflozin may be beneficial in reducing cardiovascular events in patients with type 2 diabetes and high cardiovascular risk, but may also increase the risk of amputation.
Effects of Intensive Glucose Lowering in Type 2 Diabetes
ACCORD Study Group. NEJM (June 2008)
Bottom Line: This randomized study investigated the effects of intensive therapy targeting normal glycated hemoglobin levels in patients with type 2 diabetes and established cardiovascular disease or additional risk factors. The intervention group received intensive therapy to target a glycated hemoglobin level below 6.0%, while the comparator group received standard therapy targeting a level from 7.0 to 7.9%. The primary outcome was a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes at 3.5 years of follow-up. The study included 10,251 patients with a median glycated hemoglobin level of 8.1%. The results showed no significant difference in major cardiovascular events between the two groups, but a higher mortality rate in the intensive-therapy group. Hypoglycemia requiring assistance and weight gain of more than 10 kg were more common in the intensive-therapy group. These findings suggest a previously unrecognized harm of intensive glucose lowering in high-risk patients with type 2 diabetes.
Renoprotective Effect of the Angiotensin-Receptor Antagonist Irbesartan in Patients with Nephropathy Due to Type 2 Diabetes
Lewis EJ et al. NEJM (September 2001)
Bottom Line: This randomized controlled trial, with a duration of 2.6 years, aimed to determine whether the angiotensin-II-receptor blocker irbesartan or the calcium-channel blocker amlodipine could slow the progression of nephropathy in 1715 hypertensive patients with type 2 diabetes. The intervention group received irbesartan (300 mg daily) while the comparator group received amlodipine (10 mg daily). The primary outcome was the time to a composite end point of doubling of baseline serum creatinine concentration, development of end-stage renal disease, or death from any cause. The results showed that irbesartan was associated with a 20% lower risk compared to placebo and a 23% lower risk compared to amlodipine. There were no significant differences in safety outcomes or death from any cause. The study concluded that irbesartan is effective in protecting against the progression of nephropathy in patients with type 2 diabetes, independent of its blood pressure-lowering effects.
Diabetes Trial Files Issue #DIA-2024-04
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