National Diabetic Foot Audit of England and Wales yields its first dividends
William Jeffcoate et al. Diabetic Medicine. Doi: 10.1111/dme.13191
Despite diabetes resulting in the largest cause of non-traumatic amputations, and the fact that it costs approximately £600m/ year (almost 1% of the NHS budget), it is often neglected despite NICE guidance. The quality of care provision across the UK has been examined in the first national diabetes foot audit which received data from 5000 people treated by 130 foot care teams. Of the 60% of participating commissioning organisations who could answer the questions about service structure, more than 40% of them did not have 3 of the NICE recommended systems for detecting and managing diabetic foot disease. 85% of people had foot checks within the last year, and whilst 30% of ulcer patients self-presented, more than 40% were not seen by the foot care service within 2 weeks. The longer the delay before being seen by the diabetic foot care team, the more likely were the foot ulcers to be severe. Patients who self-presented or who were seen by the specialist foot care service within two weeks of first assessment by another healthcare professional had higher rates of ulcer healing than those seen later. Despite demonstrating gaps in reporting and variation in patient care, this first audit provides a benchmark to aid service development including the reinforcement of structured care and rapid access to the specialist team.
Are there benefits for gestational diabetes mellitus in treating lower levels of hyperglycemia than standard recommendations?
Thi Hoang Lan Nguyen et al. Canadian Journal of Diabetes. Doi: http://dx.doi.org/10.1016/j.jcjd.2016.05.009
The complications of hyperglycaemia in pregnancy are well known. However, despite multiple guidelines, controversy still exists regarding the diagnostic threshold for gestational diabetes (GDM). This retrospective study reviewed outcomes in women with and without GDM. Criteria for diagnosis were stricter than current Association of Diabetes and Pregnancy Study Groups (IADPSG) guidelines and was diagnosed if fasting levels were greater than 5.0mmol/l or 2hr GTT level above 7.8mmol/l. Rates of macrosomia and pre-eclampsia were significantly higher in the group with GDM. Macrosomia, the need for insulin therapy or caesarean section and postpartum glucose intolerance predictors included pre-pregnancy body mass index, excessive gestational weight gain and OGTT screening results, although no specific threshold was found. These findings suggest a continuous association between adverse outcomes and maternal hyperglycemia and highlight the important role of maternal risk factors other than glycaemic results in the development of pregnancy-related complications. Milder forms of hyperglycemia that would not be identified by IADPSG guidelines may benefit from treatment. In summary however, this finding is similar to those from the much larger ACHOIS study so it is not clear what new evidence was provided in this paper.
The efficacy and safety of liraglutide as adjunct therapy to insulin in the treatment of type 1 diabetes (ADJUNCT ONE™)
ClinicalTrials.gov Identifier: NCT01836523
Liraglutide, an injectable glucagon-like peptide 1 receptor agonist (GLP-1RA) is a widely used therapy in type 2 diabetes with effective reduction of HbA1c combined with weight reduction and low risk of hypoglycaemia. This study examined the benefits of using it as an adjunct to therapy in patients with type 1 diabetes (T1DM). It was a 52-week, double-blind, treat-to-target trial involving 1,398 adults randomised 3:1 to receive once-daily subcutaneous injections of liraglutide (1.8, 1.2, or 0.6 mg) or placebo added to insulin. HbA1c was modestly reduced (0.34–0.54%; 3.7–5.9 mmol/mol) from a mean baseline of 8.2% (66 mmol/mol), this being significant in the two higher liraglutide doses. Insulin doses were also reduced as was mean body weight, which was clinically significant at all liraglutide doses (2.2, 3.6 & 4.9Kg). Unfortunately, the rate of symptomatic hypoglycemia increased in all groups and hyperglycemia with ketosis increased significantly for liraglutide 1.8 mg with an event rate ratio of 2.22. Although there are data that liraglutide can smooth out glycaemic variability in T1DM patients, the results from this study mean it is unlikely to be licensed for this group of patients.
Exenatide once weekly plus dapagliflozin once daily versus exenatide or dapagliflozin alone in patients with type 2 diabetes inadequately controlled with metformin monotherapy (DURATION-8)
Juan P Frías et al. The Lancet Diabetes & Endocrinology. Doi: http://dx.doi.org/10.1016/S2213-8587(16)30267-4
Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose co-transporter-2 inhibitors (SGLT2i) are hypoglycaemic drug classes which also reduce weight and improve cardiovascular (CV) outcomes. DURATION 8 examined the combination of exenatide (E: GLP-1RA) and dapagliflozin (D: SGLT2i) in 685 adults with type 2 diabetes inadequately controlled by metformin (mean HbA1c 9·3%; 78 mmol/mol). The primary endpoint was change in HbA1c from baseline to 28 weeks; various secondary endpoints included change in weight and systolic blood pressure. The reductions in HbA1c were −2·0% (E+D group), −1·6% (E only), and −1·4% (D only). E+D was significantly better than either component alone and this was also seen for all secondary efficacy endpoints. Adverse events were reported in 57% of E+D patients, 54% of E only patients and 52% of the D only group. No episodes of hypoglycaemia were reported. The authors conclude that co-initiation of the classes improves various glycaemic measures and CV risk and was well tolerated. Whether this equates to a synergistic benefit on CV outcomes requires additional long-term studies.
Intensification of diabetes therapy and time until a1c goal attainment among patients with newly diagnosed type 2 diabetes who fail metformin monotherapy within a large integrated health system
Kevin M. Pantalone et al. Diabetes Care. Doi: http://dx.doi.org/10.2337/dc16-0227
This manuscript reports United States data concerning clinical inertia, defined as ‘delay in the intensification of type 2 diabetes (T2DM) treatment among patients with poor glycemic control’. The electronic health record at the Cleveland Clinic identified patients with newly diagnosed T2DM between 2005 and 2013 who failed to reach HbA1c goal after 3 months of metformin monotherapy. Analysis was used to compare the time until HbA1c goal attainment in patients who received intensification of therapy within 6 months of metformin failure versus later intensification. The analysis was performed for HbA1c goals of (1) 7% (53mmol/mol), (2) 7.5% (58mmol/mol), and (3) 8% (64mmol/mol).
The probability of undergoing early intensification was greatest in the highest HbA1c category but was only 62%, 69%, and 72% of patients going from lowest to highest goal. The time to HbA1c goal attainment was shorter among patients who received early intensification, whatever their HbA1c goal.
Given the profile of modern second-line therapies for T2DM (regarding risk of hypoglycaemia and weight-gain), there can be little excuse for delays in intensification in patients sub-optimally controlled on metformin.