Optimal glycaemic control associated with lower pancreatic cancer risk in T2D

In patients with type 2 diabetes (T2D), optimal glycaemic control is associated with lower risks of pancreatic cancer as well as pancreatic cancer–related mortality and all-cause mortality, a territory-wide population-based retrospective cohort study has shown.

The study, conducted by researchers from the University of Hong Kong, involved 458,331 adult patients (median age, 59.8 years; male, 51.2 percent) with newly diagnosed T2D and BMI information available between January 2001 and December 2015. These patients, identified from the Hospital Authority’s Clinical Data Analysis and Reporting System, were followed from T2D diagnosis until pancreatic cancer development (primary endpoint), death, pancreatectomy, or end of study (December 2020), for a median duration of 9.9 years. [Gut 2025;doi:10.1136/gutjnl-2025-335837]

Optimal glycaemic control throughout follow-up was defined as time-weighted mean HbA_1c <7 percent, with time-weighted mean fasting glucose (FG) ≤7 mmol/L as secondary exposure.

The participants’ median time-weighted mean HbA_1c was 6.9 percent. A majority (95.5 percent) received ≥1 antidiabetic medication, primarily metformin (82.2 percent), sulfonylureas (SUs; 60.2 percent) and insulin (19.6 percent). The most common diabetes-related complication was hypertension (12.9 percent), followed by ischaemic heart disease (5.0 percent) and stroke (2.6 percent).

Substantially lower pancreatic cancer risk

The 15-year adjusted cumulative incidence of pancreatic cancer was significantly lower in participants with optimal vs suboptimal glycaemic control. The reduction in risk of pancreatic cancer was 57 percent for optimal HbA_1c control (adjusted hazard ratio [aHR], 0.43; 95 percent confidence interval [CI], 0.37–0.48) and 29 percent for optimal FG control (aHR, 0.71; 95 percent CI, 0.63–0.80).

“Optimal control of both HbA_1c and FG conferred the lowest risk of pancreatic cancer [aHR, 0.39; 95 percent CI, 0.33–0.46],” the researchers reported.

Subgroup analyses revealed lower risk of pancreatic cancer with optimal glycaemic control regardless of age (<65 and ≥65 years), sex, BMI (<25 and ≥25 kg/m²), smoking history, alcohol use disorder, Charlson Comorbidity Index (<2 and ≥2), diabetes-related complications, duration of follow-up (3–5, 5–10 and ≥10 years), physical activity, as well as use of aspirin, NSAIDs, statins, metformin, SUs or and insulin.

Additionally, the risk of pancreatic cancer increased in a stepwise manner with HbA_1c (p_trend<0.001), with aHR surging from 1.85 for HbA_1c of 7.0–7.5 percent to 4.61 for HbA_1c ≥9 percent. Every 1 percent increase in HbA_1c was associated with a 46 percent higher risk of pancreatic cancer, while each 1 mmol/L increase in FG conferred a 14 percent increase in risk.

Reduced mortality with optimal glycaemic control

Optimal glycaemic control was associated with significantly lower 15-year adjusted cumulative pancreatic cancer–related mortality vs suboptimal control. The risk reduction was 65 percent for optimal HbA_1c control (aHR, 0.35; 95 percent CI, 0.30–0.41; p<0.001) and 31 percent for optimal FG control (aHR, 0.69; 95 percent CI, 0.59–0.79).

A lower risk of all-cause mortality was also found for optimal HbA_1c control (aHR, 0.83; 95 percent CI, 0.82–0.85), but the association was not significant for time-weighted mean FG as a glycaemic control metric.

A potential oncopreventive strategy?

“These findings support the potential role of sustained glycaemic control as an oncopreventive strategy to reduce pancreatic cancer risk in patients with T2D,” the researchers wrote.

“While HbA_1c was a stronger predictor [than FG], maintaining optimal FG alongside good HbA_1c control may offer additional oncopreventive benefit,” they suggested, adding that prospective multicentre cohort studies are warranted to confirm the findings.