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Risk for CV outcomes, all-cause death varies by DPP-IV, TZD use
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In patients with type 2 diabetes, risk for cardiovascular disease, heart failure and all-cause mortality varies by diabetes drug classes, alone and combined with metformin and sulfonylurea therapy, compared with no drug treatment, according to recent findings.
“Overall, use of [DPP-IV inhibitors] or [thiazolidinediones] was associated with a decreased risk for heart failure, [CVD] and all-cause mortality compared with nonuse of these drugs,” wrote Julia Hippisley-Cox, MD, FRCGP, MRCP, professor of clinical epidemiology and general practice at University of Nottingham, United Kingdom, and Carol Coupland, PhD, MSc, professor of medical statistics in primary care at University of Nottingham. “These results, which do not account for levels of adherence or dosage information and which are subject to confounding by indication, may have implications for prescribing of diabetes drugs.”
In a population-based, open cohort study, Hippisley-Cox and Coupland analyzed data from 469,688 adults with type 2 diabetes from 1,243 general practices in England and Scotland between April 2007 and January 2015, using the QResearch database, a continually updated database of clinical and demographic data. Included patients were prescribed TZDs, DPP-IV inhibitors or insulin, alone or with metformin or sulfonylurea. Primary outcomes were incident heart failure (HF), CVD (coronary heart disease, stroke or transient ischemic attacks) and all-cause mortality. Researchers used Cox proportional hazards models to estimate HRs for diabetes treatments, adjusting for potential confounders.
Within the cohort, 274,324 (58.4%) received prescriptions for at least one diabetes drug during follow-up: 21,308 (4.5%) for TZDs; 32,533 (6.9%) for DPP-IV; 256,024 (54.5%) for metformin; 134,570 (28.7%) for sulfonylureas; 19,791 (4.2%) for insulin and 12,062 (2.6%) for other oral diabetes drugs.
Compared with nonuse, TZDs were associated with a 23% decreased risk for all-cause mortality (HR = 0.77; 95% CI, 0.71-0.84), a 26% decreased risk for HF (HR = 0.74; 95% CI, 0.66-0.83) and a 25% decreased risk for CVD (HR = 0.75; 95% CI, 0.69-0.81) after adjustment for multiple factors including sex, age, calendar year, duration of diabetes and ethnicity. For DPP-IV inhibitors, use of the drug was associated with an 18% decreased risk for all-cause mortality (HR = 0.82; 95% CI, 0.77-0.88), a 14% decreased risk for HF (HR = 0.86; 95% CI, 0.78-0.95) and no association with CVD risk (HR = 0.94; 95% CI, 0.88-1) vs. nonuse.
Researchers found interactions between TZDs and DPP-IV inhibitors, and age and HbA1c; reduced risk for all-cause mortality and CVD became “less marked” with increasing age and levels of HbA1c in both types of drugs.
Compared with no diabetes drug therapy, researchers found no link between DPP-IV inhibitor monotherapy and risk for any of the three outcomes. Dual treatment with DPP-IV inhibitors and metformin was associated with a decreased risk of all three outcomes (38% reduction in risk for HF; 33% reduction in risk for CVD; 48% reduction in risk for all-cause mortality) vs. no treatment. Triple treatment with metformin, sulfonylureas, and DPP-IV inhibitors was associated with a decreased risk for all three outcomes (40% reduction in risk for HF; 30% reduction in risk for CVD; 51% reduction in risk for all-cause mortality) vs. no treatment.
For TZDs, monotherapy was associated with a 50% decreased risk of HF vs. no treatment. Dual treatment with metformin and TZDs was associated with a decreased risk of all three outcomes (50% reduction in risk for HF; 54% reduction in risk for CVD; 45% reduction in risk for all-cause mortality) vs. no treatment. Dual treatment with sulfonylureas and TZDs was associated with decreased risk for HF (35% reduction) and CVD (25% reduction) vs. no treatment.
Triple therapy of metformin, sulfonylureas and TZDs was associated with decreased risk for all three outcomes (46% reduction in HF risk; 41% reduction in CVD risk; 56% reduction in all-cause mortality risk) vs. no treatment. – by Regina Schaffer
Disclosure: Hippisley-Cox is the co-director of QResearch, a nonprofit organization, which is a joint partnership between the University of Nottingham and Egton Medical Information System, and is a paid director of ClinRisk, which produces open- and closed-source clinical software. Coupland is a paid consultant statistician for ClinRisk.
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