Key result
Ranirestat improved proximal median sensory nerve conduction velocity compared to placebo in patients with diabetic polyneuropathy, but did not improve clinical neuropathy scores.
Why the study?
Although ranirestat had been evaluated in several randomised controlled trials for diabetic peripheral neuropathy, no meta-analysis had evaluated its efficacy and safety.
Does ranirestat improve nerve conduction velocities and clinical symptoms in patients with diabetic peripheral neuropathy?
Meta-Analysis (n=1,461)
Does ranirestat improve nerve conduction velocities and clinical symptoms in patients with diabetic peripheral neuropathy?
Ranirestat improves electrophysiologic measures of diabetic polyneuropathy but does not translate into significant clinical symptom improvement compared to placebo.
Answers are grounded in this paper and cite their sources.
Ranirestat improves nerve conduction velocity without clinical benefit in diabetic neuropathy; challenges surrogate endpoint reliance and leaves practice unchanged.
Ranirestat, an aldose reductase inhibitor evaluated in several randomised controlled trials (RCTs) in diabetic peripheral neuropathy (DPN). However, to date, no meta-analysis has evaluated the efficacy and safety of ranirestat in DPN. We undertook this meta-analysis to address this knowledge gap. Detailed search of electronic databases for RCTs published till December 2021 was done at Cochrane register, Medline, PubMed, Embase, clinicaltrials.gov, ctri.nic.in, global health and Google Scholar using the Boolean search strategy: ((ranirestat) OR (aldose reductase inhibitor)) AND ((diabetes) OR (“diabetes mellitus”)). The primary outcome was to evaluate changes in nerve conduction velocities (NCV) of different nerves. The secondary outcomes were to evaluate alterations in amplitudes, F-wave latencies of nerves, modified Toronto Clinical Neuropathy Score (mTCNS) and adverse events. Data from 5 studies involving 1461 patients with DPN was analysed to establish the impact of ranirestat (20-40 mg/day) as compared to placebo on different electrophysiologic outcomes over a median follow-up of 52 weeks. Patients receiving ranirestat had significantly greater improvement in proximal median sensory NCV [MD 0.77 m/s (95%CI: 0.50–1.05); P < 0.01; I 2 = 26%], distal median sensory NCV [MD 0.91 m/s (95%CI: 0.87–0.95); P < 0.01; I 2 = 0%], median motor NCV [MD 0.63 m/s (95%CI: 0.60–0.66); P < 0.01; I 2 = 0%], tibial motor NCV [MD 0.46 m/s (95%CI: 0.43–0.49); P < 0.01; I 2 = 0%] and peroneal motor NCV [MD 0.80 m/s (95%CI: 0.66–0.93); P < 0.01; I 2 = 0%]. mTCNS was not significantly different among groups. Treatment-emergent adverse events [risk ratio (RR) 0.85 (95%CI: 0.63–1.14); P = 0.28; I 2 = 0%] and severe adverse events [RR 1.35 (95%CI: 0.86–2.11); P = 0.20; I 2 = 0%] were comparable across study groups. In people with established DPN with long-standing diabetes, ranirestat is safe and effective in improving electrophysiologic but not clinical DPN.
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Dutta et al. (2022) conducted a meta-analysis in Diabetic polyneuropathy (n=1,461). Ranirestat vs. Placebo was evaluated on Change in proximal median sensory nerve conduction velocity (NCV) (MD 0.77, 95% CI 0.50-1.05, p=<0.01). Ranirestat improved proximal median sensory nerve conduction velocity compared to placebo in patients with diabetic polyneuropathy, but did not improve clinical neuropathy scores.
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