STEP-HFpEF: semaglutide in heart failure with preserved EF — March 2026

GenomicsKate said:

Update since I posted: I held at 1.7mg for a further twelve weeks and lost another 4kg slowly, which settles it for me.

I read this differently from GenomicsKate, on substance rather than tone. The trial means are being read too generously in this thread. STEP populations were selected, supported, and titrated by protocol, and the real-world curves are consistently a few points worse. That difference is not noise, it is what happens when you remove the study infrastructure.

GenomicsKate said:

Update since I posted: I held at 1.7mg for a further twelve weeks and lost another 4kg slowly, which settles it for me.

Mendelian randomization evidence supporting GLP-1 pathway modulation for cardiovascular risk: genetic variants in the GLP1R gene region associated with lower BMI also show associations with reduced cardiovascular risk, confirming a causal pathway[1].

This "natural experiment" (people born with genetically higher GLP-1 signaling being leaner and healthier) provides orthogonal evidence supporting the pharmacological approach. When genetic epidemiology, clinical trials, and mechanistic studies all converge, confidence in the therapeutic approach is high.

GenomicsKate said:

Update since I posted: I held at 1.7mg for a further twelve weeks and lost another 4kg slowly, which settles it for me.

Genuinely useful, thank you. I had the facts and not the framework. Adding it to my notes with a link back to this thread.

Adding the clinical framing, because it changes how the question reads.

I'm 55 years old and want to share my perspective on cardiovascular risk as an older member of this community.

My doctor was initially hesitant because of my age, but the SELECT trial included patients up to 72 and showed consistent benefit across age groups. We started at the lowest dose with closer monitoring.

8 months later: down 55 lbs, off atorvastatin, A1C from 7.0% to 5.4%. My cardiologist is thrilled. cardiovascular risk is absolutely relevant for older adults — don't let anyone tell you otherwise.

SarahChen_PharmD said:

I'm 55 years old and want to share my perspective on cardiovascular risk as an older member of this community.

Second this.