Masclee GMC, Leal I, Scotti L, De Berardis G, Bezemer I, Gil M, McGrogan A, Schmedt N, Seeger JD, Trifiro G, Pecchioli S, Pladevall-Vila M, Smits MM, Rijnbeek P, Sturkenboom M, Romio SA. Use of non-insulin blood glucose lowering drugs and the risk of acute pancreatitis. Poster presented at the 32nd ICPE International Conference on Pharmacoepidemiology & Therapeutic Risk Management; August 27, 2016. Dublin, Ireland. [abstract] Pharmacoepidemiol Drug Saf. 2016 Aug; 25(Suppl 3):246-7.

BACKGROUND: Use of noninsulin blood glucose lowering drugs (NIBGLD) has been associated with acute pancreatitis (AP). For newer NIBGLDs, including GLP1 based drugs, evidence for such risk is conflicting.

OBJECTIVES: To estimate the risk of AP for NIBGLD in databases (DB) participating in the SAFEGUARD project.

METHODS: Casecontrol study was performed nested in a cohort of new NIBGLD users. Incident AP cases were matched with up to 5 controls on DB, sex, cohort entry (± 3 months) and date of birth (± 1 year) using risk set sampling. Data were retrieved from 7 DBs from Europe (Netherlands: PHARMO; Spain: BIFAP; Germany: GePaRD; Italy: Health Search, Regional DBs of Lombardy and Puglia; United Kingdom: CPRD) and USA (Medicare). Adjusted odds ratios (ORs) and 95% confidence intervals (95%CI) were estimated per DB, comparing current use of metformin+sulfonylureas (reference) with each monotherapy, dual therapy of metformin plus another NIBGLD (not SU) and other combinations. One (ORpool) and two stage (OR meta) pooling was used to combine the database specific data.

RESULTS: In total 3,990 incident AP cases were matched to 19,543 controls. Majority of subjects were male. Drugs known to be associated with AP (class 1), gallstones and alcohol abuse increased risk of AP. Metformin monotherapy was associated with a decreased risk of AP (ORpool 0.88 95%CI:0771.00; ORmeta 0.84; 0.730.96). Regarding GLP1 based drugs, we observed a statistically nonsignificant risk for sitagliptin monotherapy (ORpool 1.53; 0.882.64; ORmeta 1.29; 0.642.58). Monotherapy of glimepiride (ORmeta 1.02;0.841.24) and glibenclamide (ORmeta 1.16;0.681.97) did not yield an increased risk. Current use of any other NIBGLDs or combinations was not associated with an increased risk of AP in any of the databases (ORpool 1.1; 0.941.34; ORmeta 1.01; 0.851.20). Recent and past use of any NIBGLD were not associated with an increased or decreased risk of AP (ORmeta 1.10; 0.881.36 and 0.93; 0.801.09, respectively).

CONCLUSIONS: Monotherapy of metformin was associated with a decreased risk of AP, while sitagliptin monotherapy was associated with a statistically nonsignificant increased risk while a risk greater than or equal to 2.6 could be excluded.