Physicians' Academy for Cardiovascular Education

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

Literature - Hippisley-Cox J, et al. BMJ 2016

Diabetes treatments and risk of heart failure, cardiovascular disease, and all-cause mortality: cohort study in primary care


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

1. Khan SS, Butler J, Gheorghiade M. Management of comorbid diabetes mellitus and worsening heart failure. JAMA 2014;311:2379-80.
2. Scirica BM, Bhatt DL, Braunwald E, et al. SAVOR-TIMI 53 Steering Committee and Investigators. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med
2013;369:1317-26.
3. Home PD, Pocock SJ, Beck-Nielsen H, et al. RECORD Study Team. Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial. Lancet 2009;373:2125-35.
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.

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