‘Clinically important’ cardiovascular benefits with antidiabetic agents
medwireNews: Research focusing on the newer oral antidiabetic agents reveals “clinically important” reductions in cardiovascular outcomes and mortality, relative to no treatment, among patients treated in primary care.
The study data, for 469,688 patients aged 25–84 years with Type 2 diabetes, come from the QResearch general practice database. As such, Julia Hippisley-Cox and Carol Coupland, from the University of Nottingham, UK, acknowledge that the findings cannot account for medication adherence and dose, or for confounding by indication.
Nevertheless, they write: “The approach we have taken allows assessment of the relative benefits and hazards of diabetes drugs in a real world clinical setting for a range of clinically important outcomes.
“It enables analysis of treatment periods that are substantially longer than those reported in clinical trials, including more events than in previous similar observational studies.”
Patients with previous prescriptions for gliptins or glitazones were excluded at baseline, leaving 32,533 (6.9%) and 21,308 (4.5%), respectively, who received them during follow-up.
Compared with no treatment, receipt of gliptins, either as monotherapy or in combination with other antidiabetic medications, was associated with a significant 14% reduction in the risk of heart failure but had no effect on the risk of cardiovascular disease.
However, there was an 18% reduction in all-cause mortality risk, which the team says is “relatively novel and deserve[s] further investigation, especially as there was no overall reduction in cardiovascular events.”
Receipt of glitazones was associated with 25% and 23% reductions in the risks of cardiovascular disease and all-cause mortality, respectively. And in contrast with randomised trial results, the researchers found no increase in heart failure risk. On the contrary, glitazone use was associated with a 26% reduced risk.
They suggest this is partly because of the “more representative” patient population in their study, and possibly also because of physicians avoiding glitazones in patients with early signs of heart failure, because of the concerns surrounding rosiglitazone.
When compared with metformin monotherapy, gliptin and glitazone monotherapy did not improve cardiovascular and mortality outcomes, in fact worsening them in two instances.
“However, since the use of gliptins and glitazones is usually recommended as a second line treatment in combination with other agents such as metformin, the clinical question is whether the addition of gliptins or glitazones to metformin monotherapy is associated with net benefit or net harm”, write Hippisley-Cox and Coupland in The BMJ.
When given with metformin, gliptin treatment was associated with significant 13% and 20% reductions in cardiovascular disease and mortality, versus metformin monotherapy, with no effect on heart failure. The corresponding reductions for glitazones were 40%, 14% and 26% – all significant.
When combined with metformin plus sulphonylureas, gliptins reduced mortality by 24% but had no effect on the other two endpoints, while glitazones were associated with significant reductions of between 21% and 32% for all endpoints.
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