Abstract 11073: Association of Antihypertensive Drug Classes, Alone or in Combination, with Incident Diabetes: A Nested Case-control Study

Abstract

BACKGROUND The impact of simultaneous use of thiazide diuretics (TD), β blockers (BB), calcium channel blockers (CCB) and renin angiotensin system blockers (RASB) on risk for diabetes mellitus (DM) is unclear, but individual agents (TD, BB) are known to be associated with increased risk.

METHODS We formed the nested cohort from Kaiser Permanente Northwest (KPNW) members between 35-65yrs and enrolled between 1997-2010. Subjects entered the cohort at the first negative DM test and were followed until loss of eligibility, diabetes onset, or study end. DM onset was based on the date of a new DM prescription, a FPG ≥ 126 mg/dl, an HgA1C≥7.0%, or a random glucose ≥200 mg/dl (index date). Eligible controls with negative DM tests within ± 6 weeks of case onset were matched in a ratio of 1:10 using incidence density sampling. Prescription dates and days’ supply were used to assess exposure to TD, BB, CCB and RASB during the 30 day window immediately prior to index date. Conditional logistic regression was used to model the association between each drug class or combination and development of DM, adjusted by covariates known to effect glucose homeostasis.

RESULTS A total of 9,097 DM cases were matched to 90,495 controls. Cases were significantly more likely to be exposed to BB (p<0.001), TD (p<0.001) and RASB (p=0.002) than controls. Combined exposure to TD and BB resulted in the fully combined diabetogenic risk of both agents (OR for interaction = 1.11, p=0.06). In contrast, combination of RASB with either TD or BB showed negative interactions, resulting in a smaller risk than the expected cumulative risk of the individual agents (Figure).

CONCLUSION In this KPNW cohort, combination of TD+BB showed increased diabetogenic risk while interactions for combinations that included a RASB were either neutral or negative. Caution should be used with TD+BB combination therapy in patients at increased risk for DM, given availability of many effective alternative therapeutic options.