Gliptins and glitazones associated with decreased risk of HF, CVD, and mortality

Hippisley-Cox J, Coupland C.
BMJ 2016;354:i3477

Background

Heart failure (HF) increases the mortality of diabetic patients dramatically. In clinical trials and post-marketing surveillance programmes, several diabetes drugs have been associated with an increase in HF risk [1-4]. There is a need to quantify risks of clinical outcomes in diabetic patients on long-term therapy with these medications.

In this open cohort study including 1243 general practices in the UK, the major clinical outcomes of 469 688 patients with type 2 DM on diabetes drugs were evaluated. Diabetes drugs included glitazones (4.5%), gliptins (6.9%), metformin (54.4%), sulphonylureas (28.7%), insulin (4.2%) and others (2.6%), as monotherapy or combination therapy and focussed on glitazones and gliptins.

Main results

Compared with non-use mono-, dual or triple therapy:

• Glitazones were significantly associated with a 23% decreased risk of all-cause mortality, a 26% decreased risk of HF, and a 25% decreased risk of CVD.
• Gliptins were significantly associated with an 18% decreased risk of all-cause mortality, a 14% decreased risk of HF, and no significant association with risk of CVD.
• The reduced risk of all-cause mortality became less apparent with increasing age and haemoglobulin A1c levels and reducing CVD risk became less apparent with increasing haemoglobulin A1c levels.
• Metformin was associated with a significant 41% decreased risk of all-cause mortality, a 30% decreased risk of HF, and a 24% decreased risk of CVD.
• Sulphonylureas were significantly associated with a 10% increased risk of all-cause mortality.
• Insulin was associated with a 47% increased risk of all-cause mortality, a 32% increased risk of HF, and a 23% increased risk of CVD.
• Other diabetes drugs were significantly associated with an 18% decreased risk of all-cause mortality.

Risks (hazard ratios) that associated to different treatment combinations, compared with periods of no diabetes drug treatment:

• There were no significant associations between monotherapy with gliptins and the risk of all-cause mortality, HF or CVD.
• Gliptin dual treatment with metformin was associated with a decreased risk of all three outcomes (reductions of 38% for HF, 33% for CVD, and 48% for all-cause mortality).
• Gliptin triple treatment with metformin and sulphonylureas, was associated with a decreased risk of all three outcomes (reductions of 40% for HF, 30% for CVD, and 51% for all-cause mortality).
• Monotherapy with glitazones was associated with a 50% decreased risk of HF.
• Glitazones dual treatment with metformin was associated with a decreased risk of all three outcomes (reductions of 50% for HF, 54% for CVD, and 45% for all-cause mortality).
• Glitazones dual treatment with sulphonylureas was associated with a decreased risk of two outcomes (reductions of 35% for HF and 25% for CVD).
• Glitazones triple treatment with metformin and sulphonylureas, was associated with a decreased risk of all three outcomes (reductions of 46% for HF, 41% for CVD, and 56% for all-cause mortality).

Conclusions

In an open cohort study of 469 688 diabetic patients, the use of gliptins or glitazones was associated with a decreased risk of heart failure, cardiovascular disease, and all-cause mortality compared with non-use of these drugs. These data may have implications for prescribing diabetes drugs in clinical practice.

Find this article online at BMJ

References

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4. Tzoulaki I, Molokhia M, Curcin V, et al. Risk of cardiovascular disease and all cause mortality among patients with type 2 diabetes prescribed oral antidiabetes drugs: retrospective cohort study using UK general practice research database. BMJ 2009;339:b4731.