Safety data in linagliptin in broad range of patients
A pooled analysis of trial data showed linagliptin was well tolerated and that the overall incidence of adverse events was similar for linagliptin compared to placebo.
The data was presented at the 49th European Association of Diabetes (EASD) annual meeting. The results from two different pooled analyses of clinical studies support previous observations that the dipeptidyl peptidase‐4 (DPP‐4) inhibitor linagliptin was shown to be well tolerated in a broad range of adults with type 2 diabetes.
Findings from a pooled comprehensive analysis of safety data in 22 linagliptin clinical trials with 7,400 people with type 2 diabetes (4,810 received linagliptin, 2,590 received placebo) included the following. Linagliptin was well tolerated overall and across all age groups studied, with a low incidence of hypoglycaemic events. In an exploratory analysis, overall hypoglycaemia was lower for linagliptin compared to placebo (11.5% versus 14%, p=0.0021).
In addition, overall incidence of adverse events (AE) or serious adverse events (SAE) with linagliptin was similar to placebo (AE 56.5% versus 61.2%, and SAE 4.8% versus 6.3%, respectively). The incidence of AEs with linagliptin compared to placebo remained similar irrespective of the age category (≤65 years, 65–74 years, ≥75 years).
Nikolaus Marx, Professor of Medicine and Cardiology, University Hospital of Aachen, Germany, said: "Drug tolerability is an important consideration in the selection of appropriate treatments for people with type 2 diabetes, as often different populations will have drug contraindications and require dose adjustments to manage their disease. The results presented today support the safety profile of linagliptin."
Results from a post‐hoc analysis of pooled data from seven clinical trials including 1,293 people with type 2 diabetes aged 65 years or older showed that linagliptin was well tolerated providing clinical efficacy in an elderly population with renal function ranging from normal to severe renal impairment. Overall renal function was not significantly altered by treatment with linagliptin from baseline to week 24, versus placebo.
Also patients taking linagliptin achieved a mean HbA1c reduction of ‐0.6% from baseline and −0.8mmol/L for fasting plasma glucose (both values placebo‐corrected).
The overall incidence of AEs with linagliptin was also similar to placebo (71.3% versus 72.8%, respectively). Incidence of investigator‐defined hypoglycaemia was not higher in patients who received linagliptin compared to those receiving placebo (21.3% versus 24.7%), with most events occurring in the trials that included a sulphonylurea or basal insulin as background therapy.
Renal and urinary AEs were experienced by 5.5% and 4.3% of linagliptin and placebo patients, respectively.
"The data presented from these analyses supplement the already established evidence demonstrating that linagliptin is a well‐tolerated treatment for a broad range of people with type 2 diabetes," said Professor Klaus.
Linagliptin (5mg) is marketed in Europe as Trajenta® (linagliptin) and in the US as Tradjenta® (linagliptin), as a once‐daily tablet that is used along with diet and exercise to improve glycaemic control in adults with type 2 diabetes.
New pooled data for empagliflozin
Pooled analysis data showed improvements in glycaemic parameters with investigational agent empagliflozin in adults with type 2 diabetes.
The pooled data were presented at the EASD annual meeting that showed treatment with investigational compound empagliflozin, a member of the sodium glucose cotransporter 2 (SGLT2) inhibitor class of drugs, improved glycaemic parameters, body weight and blood pressure, in adults with type 2 diabetes.
The pooled analysis of four phase III trials was based on efficacy data from 2,477 patients treated with empagliflozin (10mg or 25mg) for 24 weeks either as monotherapy or as add-on to metformin, metformin with sulphonylurea, or pioglitazone with or without metformin.
At week 24, patients administered empagliflozin 10mg and 25mg showed significant reductions from baseline in HbA1c of 0.70% and 0.76% respectively, compared to a change of -0.08% for placebo. There was a loss of 2.05kg and 2.25kg of body weight respectively from baseline, compared to a reduction of 0.24kg for placebo. In addition there were reductions in systolic blood pressure of 3.9mmHg and 4.3mmHg, and diastolic blood pressure of 1.8mmHg and 2.0mmHg, respectively; reductions of 0.5mmHg in systolic blood pressure and 0.6mmHg in diastolic blood pressure were achieved by patients treated with placebo; changes from baseline in LDL cholesterol of +3.1mg/dL and +3.9mg/dL respectively, versus a change of +0.8mg/dL for placebo; changes from baseline in HDL cholesterol of +2.7mg/dL for both doses, versus a change of 0.0mg/dL for placebo, and changes from baseline in triglyceride levels of -9.7mg/dL and -1.8mg/dL respectively, versus a change of +2.7mg/dL for placebo.
John E. Gerich, Professor of Medicine and Physiology, University of Rochester School of Medicine, said: "Management of type 2 diabetes in people with elevated cardiovascular risk represents a challenge for physicians. Results from this pooled analysis showed that empagliflozin was associated with reductions of elevated blood pressure and modest body weight loss, in addition to improving glycaemic parameters. These are important considerations for people with type 2 diabetes."
In addition to the pooled analysis of efficacy data, Boehringer Ingelheim and Lilly also presented the design of the empagliflozin cardiovascular (CV) outcomes trial at the EASD annual meeting.
The long-term impact of treatment with empagliflozin on CV events is being investigated in a CV outcomes event trial in patients with type 2 diabetes. The approximately four-year study of more than 7,000 patients with type 2 diabetes at elevated CV risk, is investigating the long term treatment of empagliflozin versus placebo on CV morbidity and mortality in 42 countries at more than 620 sites.
The primary endpoint is time to first occurrence of CV death, non-fatal myocardial infarction (heart attack) or non-fatal stroke. In addition, the study is assessing long-term blood glucose lowering efficacy, body weight changes, the incidence of hypoglycaemia and other safety measures. Recruitment for EMPA-REG OUTCOME™ completed in April 2013 and the study is currently expected to complete in 2018.
Life expectancy data in type 1 diabetes
Life expectancy for people with type 1 diabetes has improved substantially, and this improvement should now be reflected in life insurance and other relevant policies for those with the condition, according to researchers of a new study presented at the EASD.
The research is by Professor Helen Colhoun and Shona Livingstone, University of Dundee, UK, and colleagues on behalf of the Scottish Diabetes Research Network.
The researchers used data from the nationwide Scottish Care Information—Diabetes Collaboration database, which contains data for nearly all individuals with diabetes in Scotland. Anonymised data extracted from this database was linked with death data from the General Register. The study looked at people living with type 1 diabetes and aged 20 years or older anytime between 2008–2010.
In total, 24,971 persons aged 20 years and older were identified as living with type 1 diabetes in Scotland at any point in this three year period, among whom there were 1,079 deaths. The population with type 1 diabetes at the mid-point of the study period was 22,592 persons. In those with type 1 diabetes, the remaining life expectancy those aged 20–24 years was 45 years and 47 years for men and women respectively compared to estimates of 56 and 61 years respectively for the male and female general populations.
The remaining life expectancy for those aged 65–69 years was estimated at 12 years for both men and women compared to 17 years and 19 years for the male and female general population. The difference in remaining life expectancy between those with type 1 diabetes versus the general population reduced with increasing age. In men, the difference was 11 years at age 20–24 and five years at age 65–69. Similarly in women, the difference was 14 years at age 20–24 and seven years at age 65–69.
GetGoal-L sub-analysis results for lixisenatide
New GetGoal-L sub-analysis results showing that reductions in HbA1c with lixisenatide (Lyxumia), when added to basal insulin, were greatest in patients with type 2 diabetes who had well-controlled baseline fasting plasma glucose (FPG). These findings are consistent with the efficacy profile of lixisenatide, which shows a clinical and statistically significant reduction in HbA1c across different patient populations.
The results also showed that reductions in body weight with lixisenatide, when added to basal insulin, were greatest in this group. The GetGoal-L sub-analysis was shared during an oral presentation at the EASD.
Professor Josep Vidal, Endocrinology and Nutrition, University of Barcelona, said: "The study showed that Lyxumia is an effective post-prandial glucose lowering option that improves HbA1c levels when added to basal insulin."
As type 2 diabetes progresses over time, patients treated with basal insulin may no longer maintain their target HbA1c level (average blood sugar levels over the past 2 to 3 months) despite typically sustaining good control of FPG with basal insulin. For these patients, lixisenatide can significantly reduce HbA1c by primarily reducing post-prandial (after-meal) glucose levels through its complementary action with basal insulin. Targeting both FPG and post-prandial glucose could be an effective way to lower HbA1c in certain patients with type 2 diabetes.
Social deprivation a key factor in mortality in type 1 diabetes
Levels of social deprivation, as well as how well a patient controls their blood sugar, is an independent risk factor for mortality in people with type 1 diabetes. These are the findings of new research presented at EASD.
The research is by the Diabetes Clinical Academic Group at King’s Healthcare Partners, UK, and presented by Dr Stephen Thomas, Dept of Diabetes and Endocrinology, Guy’s and St Thomas’ Hospitals NHS Foundation Trust (GSTT), London.
Despite advances in care in recent decades, patients with type 1 diabetes continue to have increased mortality and morbidity. "In order to optimise specialist services with the aim
of improving outcomes, this study set out to determine modifiable factors that influence mortality in type 1 diabetes," says Dr Thomas.
The researchers analysed blood sugar control (HbA1c levels), demographics and health resource utilisation data collected over a 10 year period for a cohort of 1038 patients with type 1 diabetes attending two inner city London specialist diabetes outpatient clinics. (GSTT and King’s College hospital). All patients attending the service in 2002 with HbA1c data, available for each year from 2002 to 2004 and with ongoing follow-up within the clinics until 2010 were included.
The group had a mean age at baseline of 42 years and had had diabetes for a mean of 18 years. The average baseline HbA1c between 2002 and 2004 was 8.1%. In total, 37 deaths occurred by 2012 (3.6% cumulative mortality). Those who died were on average older with a higher mean baseline HbA1c (9.1%). Having a baseline HbA1c over 9.0% carried a cumulative 10-year morality that was significantly increased at 9%.
Those who died were more likely to be socially deprived, with 61% of deceased patients having scores in the poorest 20% of the population range (mean IMD score 32 points deceased versus 24 points for patients still alive). Age, HbA1c and deprivation were all independent risk factors for death of patients with type 1 diabetes.