Effects of semaglutide on walking distance, symptoms and rescue treatment by baseline medical therapy and LDL cholesterol levels: insights from the STRIDE trial
M Bonaca, A M Catarig, K C Houlind, D Krievins, K Mani, J Nordanstig, S Prabhu, Rajitha K, N Rasouli, H Sourij, S VermaAbstract
Background/Introduction
The STRIDE trial showed that semaglutide significantly improves maximum walking distance (MWD), pain-free walking distance (PFWD) and progression free survival (PFS, defined as the composite of initiation of rescue medication/revascularization, or mortality), in participants with type 2 diabetes (T2D) and symptomatic peripheral artery disease (PAD). Guideline-directed medications improve symptoms and reduce adverse outcomes in people with PAD. Whether the benefits of semaglutide in STRIDE were modified by background medications or low-density lipoprotein cholesterol (LDL-C) at baseline has not been described.
Purpose
To evaluate whether the effects of semaglutide on MWD, PFWD, and PFS are consistent across background medications and baseline LDL-C.
Methods
Qualifying participants with symptomatic PAD and T2D were randomized to semaglutide 1.0 mg sc weekly vs placebo in a blinded fashion with a primary endpoint of change in MWD at week 52. Change in PFWD was a confirmatory secondary endpoint and PFS was an exploratory analysis. Data on background medication use, and LDL-C levels were collected at baseline. Medications were categorized by class (anti-hypertensive [AHTN], anti-thrombotic [ATT], lipid lowering [LLT], and therapies for claudication ([cilostazol or pentoxifylline, CT]). Sodium-glucose co-transporter-2 inhibitors (SGLT2i) were analysed as a single class due to their glucose independent benefits. Participants were also categorized by baseline LDL-C (<1.4 mmol/L [<55 mg/dL] and <1.8 mmol/L [<70 mg/dL]).
Results
Of the 792 randomized participants, medication use at baseline was 88% AHTN, 84% LLT, 77% ATT, 35% SGLT2i, 14% CT. The proportion with LDL-C < 1.8 mmol/L (<70 mg/dL) and <1.4 mmol/L (<55 mg/dL) were 45% and 26%, respectively. The primary and secondary endpoints of change in MWD and PFWD at 52 weeks (Figure Panel A) were significantly improved with semaglutide with consistent benefit regardless of baseline medications or LDL-C. PFS was improved with semaglutide with consistent effect across baseline medications and LDL-C (Figure Panel B). Safety of semaglutide vs placebo was consistent across concomitant drug classes including SGLT2i (proportion with serious adverse events on SGLT2i at baseline: 17.1% semaglutide vs 20.5% placebo; without SGLT2i 19.6% semaglutide vs 19.4% placebo).
Conclusion(s)
Semaglutide significantly improved function, symptoms, and progression free survival in participants over 52 weeks with consistent effects regardless of baseline medications and LDL-C. Specifically, benefits for function and symptoms were present in participants already receiving medications for claudication at baseline. These findings support the use of semaglutide as medical therapy for people with symptomatic PAD and T2D and demonstrate that the effects are consistent and additive across the use of established therapies.FigureFor image description, please refer to the figure legend and surrounding text.