Effects of background statin therapy on glycemic response and cardiovascular events following initiation of insulin therapy in type 2 diabetes: a large UK cohort study

Abstract

AimStatins may increase the risk of new-onset diabetes and adversely affect glycaemic control, but their effects on the glycemic response and mortality outcomes following commencement of insulin therapy in patients with Type 2 Diabetes (T2D) are unclear.MethodsA retrospective cohort study was conducted in 12,725 insulin initiators with T2D using The Health Improvement Network (THIN) UK database. Changes in HbA1c at 6, 12, 24 and 36 months, and the 5-year risk of mortality and (3-point) major adverse cardiovascular events (MACE), were compared between prior users (n = 10,682) and non-users (n = 2043) of statin therapy who were newly commenced on insulin treatment. Cox proportional hazard models were used to estimate the hazard ratios of the different outcomes.ResultsMean age of the cohort was 58.7 ± 14.0 years (51% male) and mean baseline HbA1c was 8.7 ± 1.8%. A greater initial reduction in HbA1c was observed following insulin initiation in the non-users of statins compared with the users, which was significant in the short term (−0.34% vs −0.26% at 6 months; mean diff = −0.09%, p = 0.004) but not in the long term: −0.31% versus −0.35% at 3 years (mean diff = 0.05%, p = 0.344). CV events (3-point MACE) were 878 versus 217 in statin users versus non-users (20.7 vs 30.9 per 1000 person-years; adjusted Hazard Ratio (aHR) 1.36 (95% CI 1.15–1.62; p < 0.0001). In a subgroup analysis of individual statins, HbA1c was higher throughout the study duration with all statins relative to non-users of statin therapy (p < 0.05). The aHRs for 3-point MACE for atorvastatin, simvastatin, rosuvastatin and pravastatin were 0.82 (95% CI 0.68–0.98), 0.67 (0.55–0.82), 0.56 (0.39–0.81) and 0.78 (0.60–1.01), respectively.ConclusionsFollowing initiation of insulin therapy in patients with T2D in routine care, concurrent use of a statin was associated with less good glycaemic control in the short-term but a much lower risk of major adverse CV events.Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-017-0587-6) contains supplementary material, which is available to authorized users.

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“…In Western medicine, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have been used effectively in patients with primary or secondary ischaemic heart disease, hypercholesterolaemia, and cardiovascular disease, although various side effects have been reported (Anyanwagu et al. 2017). The most common adverse reaction is myalgia, which affects approximately 10% of patients with myasthenia.…”

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“…Overall evidence show that the benefits of statins far outweigh the potential hazards [ 19 – 21 ]. Statin therapy was associated with less good glycemic control in diabetes and pre-diabetes, but there was a much lower risk of major cardiovascular events [ 22 , 23 ]. Real-world studies consistently indicate that statins are frequently suboptimal and under prescribed in populations with high cardiovascular risk [ 24 – 27 ].…”