Treatment outcomes with oral anti-hyperglycaemic therapies in people with diabetes secondary to a pancreatic condition (type 3c diabetes): A population-based cohort study

Objectives Diabetes secondary to a pancreatic condition (type 3c diabetes) affects 5-10% of people with diabetes, but evidence on the efficacy and tolerability of oral therapies in this group are lacking. We aimed to assess short-term treatment outcomes with oral anti-hyperglycaemic therapies in people with type 3c diabetes. Design Population-based cohort study. Setting UK primary care records (Clinical Practice Research Datalink; 2004-2020), linked hospital records. Participants 7,084 people with a pancreatic condition (acute pancreatitis, chronic pancreatitis, pancreatic cancer, haemochromatosis) preceding diabetes diagnosis (type 3c cohort) initiating an oral glucose-lowering therapy (metformin, sulphonylureas, SGLT2-inhibitors, DPP4-inhibitors, or thiazolidinediones [TZDs]), without concurrent insulin treatment. This cohort was stratified by evidence of pancreatic exocrine insufficiency [PEI] (1,167 with PEI, 5,917 without) and matched to 97,227 type 2 diabetes (T2D) controls. Main outcome measures 12-month HbA1c change and treatment discontinuation within 6 months, in the type 3c diabetes cohort compared to T2D controls. Results People with type 3c diabetes had a substantial mean HbA1c reduction with oral therapies in those with PEI (9.4 mmol/mol [95%CI 8.9 to 10.0]) and without (12.2 mmol/mol [12.0 to 12.4]). Compared to T2D controls, people with type 3c diabetes without PEI had a similar mean HbA1c reduction (0.7 mmol/mol [0.4 to 1.0] difference) and similar odds of early treatment discontinuation (Odds ratio [OR] 1.08 [0.98 to 1.19]). In contrast, people with type 3c diabetes and PEI had a lower mean HbA1c response (3.5 mmol/mol [2.9 to 4.1] lesser reduction), and greater discontinuation (OR 2.03 [1.73 to 2.36]). Results were largely consistent across type 3c subtypes and individual drug classes. Conclusions Oral anti-hyperglycaemic therapies are effective in people with type 3c diabetes, and could provide an important component of glycaemic management. However, the presence of PEI is associated with modestly reduced glycaemic response and reduced tolerability, meaning PEI could identify people that may benefit from closer monitoring after initiating oral therapy.