Topline data from a 24‑week phase 3 for an oral GLP‑1 analog show about 1.1% A1c reduction over placebo but higher discontinuations from GI events (11% vs 4%) and a small retinopathy signal in rapid reducers. For those involved in protocol or label planning, would you push for baseline ophthalmic screening and slower up‑titration to mitigate risk, or is the benefit–risk acceptable as is?
I’d bake in baseline eye screening only for patients with known DR or baseline A1c ≥9% and mandate a “start low, go slow” 4–6 week uptitration. In our clinic, a week‑2 check‑in with the option to hold the next step and PRN ondansetron cut GI dropouts by about a third. Caveat: universal screening will bottleneck access, so trigger an urgent exam if A1c drops >1% by week 8 or any visual symptoms emerge.
That 11% vs 4% GI discontinuation gap is what kills adherence — . @b_sanders1973 I’d keep your slow titration and add a guardrail: if A1c drops >1% by week 4, hold the dose 2 more weeks and get same-day tele-retina for anyone with known DR or baseline >=9%. One tweak that’s helped us: a ‘pause, don’t quit’ plan plus PRN ondansetron during the first escalation cut early drop-outs in half.
I’ve found that starting with a lower dose and extending the uptitration period can really help with tolerability, especially when GI issues come into play, as you pointed out with the 11% discontinuation rate. In my practice, we also schedule a follow-up at the two-week mark to address any concerns, which seems to help patients feel more supported. Have you considered the impact of patient education on adherence?