The 70th Scientific Sessions of the American Diabetes Association

Saxagliptin plus metformin non-inferior to SU plus metformin
Saxagliptin plus metformin is non-inferior to titrated sulphonylurea (SU) plus metformin in reducing HbA_1c levels in people with type 2 diabetes, according to the results of a 52-week, phase IIIb study. The results were announced by Bristol-Myers Squibb and AstraZeneca at the American Diabetes Association’s 70th Scientific Sessions.

Those treated with saxagliptin reported significantly fewer hypoglycaemic events and significant weight loss compared with those in the glipizide group.

Participants of the 52-week study were adults with type 2 diabetes who had inadequate glycaemic control on metformin monotherapy plus exercise. Saxagliptin 5 mg was added to metformin therapy, and compared with titrated glipizide plus metformin therapy.

Those taking saxagliptin achieved an adjusted mean change in HbA_1c from baseline of –0.74 percentage points (8.1 mmol/mol).

BARI-2D: No increased risk of CV events with rosiglitazone
Rosiglitazone was not associated with an increased risk of death, stroke or heart attack in results from BARI-2D (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes), presented at the 70th Scientific Sessions in Orlando. The study does, however, confirm the increased risk of fractures associated with this treatment.

Analysing 4.5 years of follow-up data for participants treated with rosiglitazone, the study found no increase in risk of death from heart attack. In fact, the rate of death, heart attack and stroke was about 28% lower among people taking rosiglitazone compared with the control group who were not taking a thiazolidinedione (TZD). As has been seen in other studies of TZDs, the rate of congestive heart failure was higher among people taking rosiglitazone, but this was not statistically significant.

The lead researcher, Richard Bach, Associate Professor of Medicine at the Washington University School of Medicine said: “I think these data are important because they suggest there is no significant cardiovascular harm posed by taking rosiglitazone for patients with type 2 diabetes and coronary heart disease.”

Insulin degludec can effectively control blood glucose levels
Phase II studies have confirmed that insulin degludec can improve glycaemic control, announced Novo Nordisk at the 70th Scientific Sessions of the American Diabetes Association. The ultra-long-acting basal insulin demonstrated the potential to help achieve target glycaemic control when used once daily or three-times weekly in people with type 2 diabetes.

In one study, after 16 weeks of treatment with insulin degludec, mean HbA_1c reductions were similar across the once-daily and three-times-weekly insulin degludec groups (–1.3 and –1.5 percentage points [–14.2 and –16.4 mmol/mol], respectively) and were comparable to insulin glargine (–1.5% [16.4 mmol/mol]).

“Insulin degludec has shown the potential to help deliver improvements in glycaemic control with less than one daily injection”, said Mads Krogsgaard Thomsen, Executive Vice-President and Chief Science Officer at Novo Nordisk.

In addition, 77% of people treated with insulin degludec three times per week did not experience confirmed hypoglycaemia (low blood glucose levels or episodes that required assistance), which was similar to those in the insulin glargine group. Of participants administering insulin degludec once daily, 92% did not experience confirmed hypoglycaemia.

Sensor-augmented insulin pump improves glycaemic control
Results from a study of sensor-augmented insulin pump therapy in type 1 diabetes have shown that adults and children using the therapy experienced an improvement in glycaemic control without an increase in hypoglycaemia compared with multiple daily injections (MDI). These data, announced at the 70th Scientific Sessions in Orlando, showed how mean HbA_1c levels reduced from 8.3% (67 mmol/mol) at baseline to 7.5% (58 mmol/mol) in the sensor-augmented group compared with 8.1% (65 mmol/mol) in the MDI group by study end.

The results demonstrated a link between sensor use and increased benefit: those who used the sensor more than 81% of the time reduced their HbA_1c level by 1.2 percentage points (13.1 mmol/mol).

ACCORD: No overall reduction in cardiovascular risk
Neither intensive lowering of blood glucose, intensive lowering of blood pressure nor treatment of blood lipids reduced cardiovascular risk in people with type 2 diabetes at high risk for cardiovascular events, according to 5-year results of the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial.

However, the results, announced at the 70th Scientific Sessions in Orlando, did show improvements to microvascular conditions, such as the progression of retinopathy, visual acuity, renal and nerve function.

“In these ACCORD participants with established type 2 diabetes and additional risk factors for cardiovascular disease, intensive lowering of blood glucose reduced some markers of eye, nerve and kidney disease compared with standard glucose control, but the groups did not differ in the rate of progression to kidney failure, nerve disease, and major vision loss”, said lead author Faramarz Ismail-Beigi of Case Western Reserve University, Cleveland.

The ACCORD Study Group also cautioned that any potential benefits must be weighed against the increased risk of mortality and hypoglycaemic episodes that were seen to accompany intensive lowering of blood glucose levels.

“Within this group, it’s important for patients and doctors to decide the highest priority for the patient”, said Denise Simons-Morton from the National Institutes of Health. “Is improved eye health worth a higher risk of death and low blood sugar episodes? That’s a question only a fully informed patient can answer”, she said.

Linagliptin reduces blood glucose compared with placebo
New linagliptin phase III data were presented at the 70th Scientific Sessions of the American Diabetes Association, showing that this investigational compound – a dipeptidyl peptidase-4 inhibitor – achieved significant and clinically meaningful reductions in blood glucose that were sustained over 24 weeks compared with placebo.

Statistically significant changes in HbA_1c were observed with linagliptin (5 mg) monotherapy versus placebo (–0.69 percentage points [7.5 mmol/mol]; P<0.0001) and when used in combination with other commonly-used oral antidiabetes drugs including metformin (–0.64 percentage points [7.0 mmol/mol]; P<0.0001), and metformin plus a sulphonylurea (–0.62 percentage points [6.8 mmol/mol]; P<0.0001).

“What is of particular interest to both patients and clinicians is that this data shows that linagliptin provides good glycaemic control, low risk of hypoglycaemia and is weight neutral from a once-daily 5 mg dose”, said Anthony Barnett, Professor of Medicine and Clinical Director of the Department of Diabetes and Endocrinology, University of Birmingham and Heart of England NHS Foundation Trust, Birmingham.

Exenatide extended release: Efficacy and tolerability data
Results of a pooled analysis investigating the safety and tolerability of a once-weekly preparation of exenatide were announced at the 70th Scientific Sessions in Orlando. The investigational glucagon-like peptide-1 receptor agonist was generally well-tolerated with a low rate of discontinuation due to serious adverse events.

The pooled safety data originated from three randomised controlled trials (DURATION 1, 2 and 3) involving people treated with exenatide extended release (ER) compared with various other diabetes treatments including sitagliptin, pioglitazone or insulin glargine.

The overall incidence of adverse events (AEs), serious AEs and discontinuations due to serious AEs were similar for exenatide ER versus pooled comparators. AEs occurred in 77% of participants receiving exenatide ER versus 71% for pooled comparators; serious AEs were 4% for exenatide ER versus 5% for pooled comparators; and discontinuations due to serious AEs were less than 1% for both groups.

Results for DURATION 2 and DURATION 3 were also announced at the Scientific Sessions and published simultaneously in The Lancet.

DURATION 2 was a 26-week, randomised, double-blind superiority study that compared exenatide ER with sitagliptin or pioglitazone as add-on therapy to metformin in 491 people with type 2 diabetes. Reduction in HbA_1c was significantly greater with exenatide ER compared with sitagliptin (difference in HbA_1c –0.6 percentage points [6.6 mmol/mol];P<0.0001) and pioglitazone (–0.3 percentage points [3.3 mmol/mol]; P<0.0001).

DURATION 3 was a 26-week, randomised, open-label, parallel study comparing exenatide ER with insulin glargine. Change in HbA_1c at 26 weeks was greater in participants taking exenatide ER (n=228) than in those taking insulin glargine (n=220), with a difference of HbA_1c −0.16 percentage points (1.7 mmol/mol).

Commercial artificial pancreas on the horizon
The artificial pancreas could become commercially available within the next few years, according to speakers at the joint American Diabetes Association and Juvenile Diabetes Research Foundation symposium at the 70th Scientific Sessions in Orlando.

The artificial pancreas developed and tested at Cambridge Metabolic Research Laboratories has recently been shown to control overnight blood glucose levels following consumption of a large meal and glass of white wine.

Participants of the study spent 70% of the night time within target glucose range when using the artificial pancreas, compared to 47% of the time without using the artificial pancreas. No hypoglycaemic events occurred when participants were treated with the artificial pancreas.