Dipeptidyl peptidase-4 inhibitors and cardiovascular risks in patients with pre-existing heart failure
Shuo-Ming Ou et al. Heart. Doi:10.1136/heartjnl-2016-309687
Launched 9 years ago, the Dipeptidyl peptidase-4 inhibitors (gliptins) have rapidly found favour amongst clinicians treating Type 2 diabetes and, following NICE guidance can be positioned as second line agents after Metformin. Recent cardiovascular studies have shown them to be generally safe although Saxagliptin was associated with an unexpected 27% increase in admissions to hospital from heart failure, an issue not demonstrated with other gliptins. This insurance database Taiwanese study looked at the impact of gliptins on high risk patients with established heart failure. Reassuringly, the risk of hospitalisation from heart failure was not increased. Interestingly, the risks of mortality and the combination of MI and ischaemic stroke were lower for patients receiving DPP-4 inhibitors although the mechanism for this remains unclear. Overall, this and other studies suggest that the class is safe although, in patients with normal renal function, an SGLT2 may be a more appropriate option especially for patients where heart failure may be an issue.
Follow-up of blood-pressure lowering and glucose control in Type 2 Diabetes
Zoungas et al. NEJM. Doi: 10.1056/NEJMoa1407963
After completion of DCCT (young patients with T1DM), UKPDS (newly diagnosed T2 patients) studies, post-trial or legacy results have recently been published. In these legacy studies, the groups previously randomised to intensive glucose control continued to show a reduction in micro and macrovascular disease – in UKPDS glucose control became significant. In the ADVANCE study, a single tablet of Perindopril-Indapamide reduced the risk of macrovascular disease whilst intensive glucose lowering reduced the risk of micro and macrovascular disease, the latter primarily due to its impact on nephropathy in this latest 6 year follow up of the ADVANCE patients. In the blood pressure lowering group, the risk of death from a cardiovascular event, although attenuated was still significant whilst there was no evidence that intensive glucose lowering had a long term impact on macrovascular events. Whilst this does seem to differ from UKPDS legacy, in the ADVANCE study, the patients had a lower baseline. Although this fell during the study, it did not fall further afterwards unlike the UKPDS patients. Furthermore, more effective cardiovascular prevention (including lower lipid targets) may have added to the lack of effect on glucose lowering long term.
Early diabetes screening in women with previous gestational diabetes: a new insight
Aline Nabuco et al. Diabetology & Metabolic Syndrome. Doi: 10.1186/s13098-016-0172-2
Gestational diabetes (GDM) is a risk factor for the development of Type 2 diabetes with approximately 40-50% of patients developing the condition within 10 years of delivery. Although GDM usually resolves post-partum, NICE recommends screening for T2DM approximately 6 weeks after delivery despite the fact that the oral glucose tolerance test (OGTT) is a more sensitive method. Whilst 6 weeks post-partum seems to have been chosen as it fits in with other post-natal testing, this study examined the glucose tolerance of GDM patients 48-72 hours post-partum and its correlation with a 6 week OGTT. They found that fasting and 2 hour OGTT glucose levels of 4.3 and 7.2mmol/l respectively were optimal levels to screen for dysglycaemia after GDM complicated pregnancies and that the 2hour OGTT was more accurate than fasting glucose in predicting this. Whilst this study confirms the benefit of the OGTT in screening for T2DM, in the UK, recommendations from NICE moving towards fasting glucose and HbA1c may miss significant numbers of at risk women.
Patterns of anti-diabetic medication use in patients with T2DM in England and Wales
Preeti Datta-Nemdharry et al. Pharmacoepidemiology and Drug Safety. Doi: 10.1002/pds.4092
In 2009 the National Institute for Health and Care Excellence (NICE) produced guidelines for management of hyperglycaemia in type 2 diabetes (T2DM). These could be distilled down to a preferred sequence of metformin, sulphonylurea and (human) basal insulin with options at each treatment escalation. This study sought to examine how well the guidance was followed in England & Wales between 2000-12 using data from the Clinical Practice Research Datalink. 123,671 patients, 56% males, 95% aged over 40 years and 79% with at least one recorded HbA1c level were included. Metformin was first prescription for 80% of patients (mean HbA1c 71.4 mmol/mol [8.68%]) whilst 16% received sulphonylurea first-line (mean HbA1c 78.3 [9.31%]). Patients initially prescribed insulin had mean HbA1c 84.6 [9.89%]. The authors state that 78% patients were managed in line with NICE, ignoring the fact that most of the observation period pre-dated the recommendations from NICE and that prior to 2007 treatment options were limited (incretin agents were not available). Furthermore, levels of HbA1c at therapy initiations were much higher than NICE recommended.
Blood pressure and complications in individuals with type 2 diabetes and no previous cardiovascular disease
Samuel Adamsson Eryd et al. BMJ. Doi: http://dx.doi.org/10.1136/bmj.i4070
Systolic blood pressure (SBP) targets for people with type 2 diabetes (T2DM) have become controversial with levels in US guidelines now set at 140mmHg, higher than was previously the case. This follows on from the ACCORD BP trial which failed to show any benefit from tight control of SBP (<120mmHg) versus standard treatment (~ 135mmHg). This is not the case in non-diabetics, however, where the SPRINT trial, showed that targeting SBP less than 120mmHg led to lower rates of cardiovascular disease (CVD) and all-cause death. This population based cohort study adds to the debate. It followed 187,106 Swedish T2DM patients aged less than 75 years for a mean of five years. Clinical events were obtained from hospital discharge and death registers and hazard ratios estimated for different levels of baseline SBP. The group with the lowest SBP (110-119 mm Hg) had a significantly lower risk of CVD than the reference group (130-139 mm Hg), implying that current targets are too high. One caution; this study cohort had no previous CVD, suggesting that targets need to be individualised.