Aim To assess whether adding empagliflozin to closed‐loop automated insulin delivery could reduce the need for carbohydrate counting in type 1 diabetes (T1D) without worsening glucose control. Materials and Methods In an open‐label, crossover, non‐inferiority trial, 30 adult participants with T1D underwent outpatient automated insulin delivery interventions with three random sequences of prandial insulin strategy days: carbohydrate counting, simple meal announcement (no carbohydrate counting) and no meal announcement. During each sequence of prandial insulin strategies, participants were randomly assigned empagliflozin (25 mg/day) or not, and crossed over to the comparator. Mean glucose for carbohydrate counting without empagliflozin (control) was compared with no meal announcement with empagliflozin (in the primary non‐inferiority comparison) and simple meal announcement with empagliflozin (in the conditional primary non‐inferiority comparison). Results Participants were aged 40 ± 15 years, had 27 ± 15 years diabetes duration and HbA1c of 7.6% ± 0.7% (59 ± 8 mmol/mol). The system with no meal announcement and empagliflozin was not non‐inferior (and thus reasonably considered inferior) to the control arm (mean glucose 10.0 ± 1.6 vs. 8.5 ± 1.5 mmol/L; non‐inferiority p = .94), while simple meal announcement and empagliflozin was non‐inferior (8.5 ± 1.4 mmol/L; non‐inferiority p = .003). Use of empagliflozin on the background of automated insulin delivery with carbohydrate counting was associated with lower mean glucose, corresponding to a 14% greater time in the target range. While no ketoacidosis was observed, mean fasting ketones levels were higher on empagliflozin (0.22 ± 0.18 vs. 0.13 ± 0.11 mmol/L; p < .001). Conclusions Empagliflozin added to automated insulin delivery has the potential to eliminate the need for carbohydrate counting and improves glycaemic control in conjunction with carbohydrate counting, but does not allow for the elimination of meal announcement.

Award programmes that acknowledge the remarkable accomplishments of long-term survivors with type 1 diabetes have naturally evolved into research programmes to determine the factors associated with survivorship and resistance to chronic complications. In this review, we present an overview of the methodological sources of selection bias inherent in survivorship research (selection of those with early-onset diabetes, incidence-prevalence bias and bias from losses to follow-up in cohort studies) and the breadth and depth of literature focusing on this special study population. We focus on the learnings from the study of longstanding type 1 diabetes on discoveries about the natural history of insulin production loss and microvascular complications, and mechanisms associated with them that may in future offer therapeutic targets. We detail descriptive findings about the prevalence of preserved insulin production and resistance to complications, and the putative mechanisms associated with such resistance. To date, findings imply that the following mechanisms exist: strategies to maintain or recover beta cells and their function; activation of specific glycolytic enzymes such as pyruvate kinase M2; modification of AGE production and processing; novel mechanisms for modification of renin-angiotensin-aldosterone system activation, in particular those that may normalise afferent rather than efferent renal arteriolar resistance; and activation and modification of processes such as retinol binding and DNA damage checkpoint proteins. Among the many clinical and public health insights, research into this special study population has identified putative mechanisms that may in future serve as therapeutic targets, knowledge that likely could not have been gained without studying long-term survivors.