In the US, >90% of people with T2DM on oral antihyperglycemics use secretagogues. The present analysis is the first to quantify the real-world, US frequency of Level 3 severe hypoglycaemia (SH) in this population. Longitudinal, prospective data were leveraged from the iNPHORM study. Adults (≥18 years old) with secretagogue-treated T2DM (not on insulin) were recruited from a US-wide, probability-based internet panel. Data on participant characteristics and Level 3 SH occurrence were captured across a screener, baseline and 12 monthly follow-ups. Multivariable negative binomial regression with cluster bootstrapping for repeated measures modelled the annualized rate of SH for individuals completing ≥1 follow-up(s). A repeated lasso regression ‘voting’ procedure selected all risk factors. Multiple imputation addressed missingness. Of the 353 respondents (male: 51.1%; age: 54.6 [SD: 13.2] years; diabetes duration: 10 [IQR: 12] years; retention rate: 84.4%), the incidence proportion of SH over follow-up was 21.8 (95% CI: 17.8-26.3)%, and the rate was 3.8 (95% CI: 2.5-5.7) events per person-year. Our final model included age, continuous/flash glucose monitoring use, corticosteroid use, number of healthcare visits, fear of hypoglycemia, number of past-year SH requiring hospital care, retinopathy, and other diabetes complications. The rate of annualized Level 3 SH statistically increased with younger age, more frequent healthcare visits, greater fear of hypoglycemia, higher number of past-year healthcare-related SH, and presence of retinopathy. Our results indicate disturbingly high incidences of Level 3 SH among secretagogue users. Whenever logical and feasible, clinicians should prioritize one of the many other available antihyperglycemics that confer little to no hypoglycemia risk. Else, other hypoglycemia prevention strategies—risk-tailored to this ubiquitous T2DM population—are urgently warranted.


A.Ratzki-leewing: Consultant; Novo Nordisk, Eli Lilly and Company, Research Support; Sanofi. J.E.Black: None. G.Zou: None. B.L.Ryan: None. S.B.Harris: Advisory Panel; Bayer Inc., AstraZeneca, Eli Lilly and Company, Dexcom, Inc., Novo Nordisk A/S, Novo Nordisk Canada Inc., Sanofi, Consultant; Abbott Diabetes, Janssen Pharmaceuticals, Inc., Other Relationship; American Diabetes Association, Research Support; Abvance Therapeutics, Canadian Institutes of Health Research.


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