Building Competency in Diabetes Education THE ESSENTIALS

TREATMENT MODALITIES: PHARMACOLOGICAL THERAPIES I 6-19

• 26% reduction in CV death, non-fatal MI or non-fatal stroke • 39% reduction in non-fatal stroke • 26% reduction in non-fatal MI • No significant impact on all-cause mortality • NNT: 45 people for two years to prevent one MACE event

SUSTAIN-6 was not powered to determine CV benefit superiority, therefore results of SUSTAIN-6 are graded lower than LEADER.

However, in the SUSTAIN-6 trial, semaglutide was associated with higher rates of diabetic retinopathy complications vs. placebo (HR 1.76; 95% CI 1.11-2.78; p=0.02).

Sub-analysis of the SUSTAIN 6 trial revealed that the people that developed diabetic retinopathy complications in the study had higher A1C at baseline, pre-existing diabetic retinopathy at baseline, and were more likely taking insulin. Treatment with semaglutide resulted in a rapid improvement in A1C during the first 16 weeks vs placebo. When subjects with pre-existing retinopathy were removed, the rates of retinopathy were similar between groups. Retinal complications were more likely to be seen in people who had a significant reduction in A1C (1.5% vs 0.5%) in both treatment arms (32). It is well known in clinical practice that a rapid improvement in A1C with insulin can increase the risk of worsening retinopathy in people at risk. The Re searching Cardiovascular Events With a W eekly In cretin in D iabetes (REWIND) was the first major cardiovascular outcome trial (CVOT) to have a majority of its participants as primary prevention, in contrast to most CVOT which mainly included participants with a history of CV disease. Population: Type 2 diabetes • ≥50 y.o. with a previous CV event; OR • ≥60 y.o. with at least 2 CV risk factors (hypertension, tobacco use, abdominal obesity or dyslipidemia); 68.5% did NOT have established CVD Notably, unlike other CVOTs where baseline A1C was ≥8.0%, REWIND had a baseline A1C median of 7.2% with 25% having a baseline A1C of less than 6.6% Treatment with dulaglutide 1.5mg resulted in a: • 12% reduction in MACE (CV death, non-fatal MI or non-fatal stroke)