Damian McNamara, MA

VANCOUVER, Canada — Use of sodium glucose cotransporter-2 (SGLT2) inhibitors is associated with a reduced risk of gastrointestinal (GI) cancers among patients with type 2 diabetes compared to dipeptidyl peptidase IV (DPP4) inhibitors, new evidence reveals.

The SGLT2 inhibitors emerged superior to DPP4 inhibitors for reducing risk of colorectal, hepatic, esophageal, and other GI cancers except pancreatic cancer, said study investigator Shu-Yen Emily Chan, MD, a gastroenterologist in the Departments of Medicine and Epidemiology at Weiss Memorial Hospital in Chicago.

On the basis of the findings, physicians could consider the SGLT2s canagliflozin, dapagliflozin, and empagliflozin or a GLP-1 as first-line therapy, particularly for people with T2D who are at elevated risk for GI cancers, Chan said in an interview here at the American College of Gastroenterology (ACG) 2023 Annual Scientific Meeting.

Previous research focused on potential cardiovascular or renal benefits associated with SGLT2s, "but there are few looking at GI cancer risk and these medications," she added. Most earlier studies in cancer have been preclinical and observational studies on colorectal cancer or hepatocellular carcinoma.

Using the TriNetX database of millions of medical claims from 92 hospitals across the United States, Chan and colleagues identified 706,390 adults who began first-line SGLT2 inhibitor therapy. They used propensity matching to link these patients with 706,390 other adults who began taking a DDP4 inhibitor (sitagliptin, saxagliptin, linagliptin, or alogliptin).

All participants had been diagnosed with type 2 diabetes. Patients were prescribed an SGLT2 inhibitor at least three times, and any cancer diagnosis that occurred at least 6 months after starting therapy was noted. Anyone with a history of cancer, cancer recurrence, or metastatic disease was excluded from the population-based cohort study.

In addition to evaluating a large number of patients, the study is notable for including people with ulcerative colitis and Crohn's disease and for evaluating every GI cancer — esophageal, gastric, small intestinal, colorectal, rectal, anal, hepatic, biliary, and gallbladder malignancies.

Key Findings

Among adults who received an SGLT2 inhibitor, there was a 15% decrease in overall risk of developing any GI cancer compared to those who received a DPP4 inhibitor (hazard ratio [HR], 0.85; 95% CI, 0.82 – 0.88).

Colon cancer was the most common malignancy in the study. Chan and colleagues identified colon cancer among 1789 people, or 0.25% of those taking an SGLT2 inhibitor, compared with 3283 people, or 0.46%, of those taking a DPP4 inhibitor.

SGLT2 inhibitors were associated with a 16% decrease in risk of gastric cancer (HR, 0.84; 95% CI; 0.74 – 0.945; P = .005), a 13% decrease in risk of liver and intrahepatic bile duct cancer (HR, 0.87; 95% CI, 0.81 – 0.95), and a 22% decrease in risk of colon cancer (HR, 0.781; 95% CI, 0.74 – 0.83; P < .001) compared to the DPP4 medications.

The only cancer more likely in the SGLT2 inhibitor group than in the DPP4 inhibitor group was pancreatic cancer (HR, 1.035; 95% CI, 0.964 – 1.111; P = .340).

The SLGT2 inhibitor class also was superior to metformin for reducing risk of GI cancers.

Asked whether the study findings should alter current practice, Chan said that the study is new and hasn't yet been published. "More studies will be needed and included in official guidelines before the findings become practice-changing," she said.

Limitations of the study include residual confounding, absence of family cancer history, and information bias. Strengths include the large, national database and propensity score matching.

"Eye-Opening" Study

"It is a good study, and eye-opening because it shows that one class of diabetes medications is better than another one," said session co-moderator Kenneth J. Vega, MD, professor of medicine and chief of the Division of Gastroenterology and Hepatology at Augusta University–Medical College of Georgia.

Vega shared his theory on why diabetes medications could reduce risk of GI cancers. "I would think reducing diabetes means you can control inflammation...and better controlling inflammation leads you to have less cancers."

He added, "I think we need more long-term studies."