Blood pressure (BP) lowering or intensive glucose control does not significantly reduce the incidence and progression of diabetic retinopathy, report researchers in the journal Diabetologia.

The ADVANCE Retinal Measurements (AdRem) study did find significant reductions in some retinal lesions with both interventions, however.

Raised levels of both BP and blood glucose are associated with an increased risk for diabetic retinopathy. AdRem is a substudy of the ADVANCE (Action in Diabetes and Vascular disease) study evaluating the effects of target driven intensive glucose control and placebo-controlled BP lowering on retinal vascular changes.

A total of 1241 patients had gradeable seven-field stereoscopic retinal photographs of both eyes available at baseline and the final visit. The primary outcome was the incidence and progression of retinopathy as assessed by at least two steps of progression in the Early Treatment of Diabetic Retinopathy Study (ETDRS) classification.

The team led by Joline Beulens (University Medical Center Utrecht, The Netherlands) reported that retinopathy progressed in 59 (4.8%) patients and developed in 128 (10.3%) patients during a median follow-up of 4.1 years.

Neither BP lowering nor intensive glucose-lowering therapy significantly reduced the incidence and progression of retinopathy, although both treatments were associated with trends towards benefits.

Any retinal vascular lesion occurred at a similar frequency among patients receiving BP lowering treatment and those on placebo. However, BP lowering treatment did significantly reduce the occurrence of macular edema, the most common cause of vision loss in patients with diabetes, and arteriovenous nicking, compared with placebo.

There was no difference in any of the specified retinal lesions between intensive glucose lowering and usual treatment. But, after adjusting for the presence of retinal hemorrhages at baseline, intensive glucose lowering was associated with lower risks for microaneurysms, hard exudates, and macular edema, although these differences were of borderline significance.

“A longer period of active treatment and larger numbers of patients are needed to demonstrate more definitive benefits,” the authors conclude.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

Free abstract

When self-monitoring of blood sugar levels was first introduced, health care practitioners believed glucometers would be useful to educate people with type 2 diabetes. How? Well they thought by type 2 diabetics checking their sugar levels after eating carbohydrate foods, or exercising, they would learn “a good pattern of behavior”. However, many studies have found this did not happen.

There appears to be a lot of controversy as to whether diabetics who self-monitor actually see an improvement in their glycemic control. Apparently many people check their levels three or four times a day but then make no changes in their eating plan when their results are abnormal. Many studies investigating the value of self monitoring of blood sugars in diabetics whose levels are controlled by diet or oral medications, have not shown that this testing leads to improved diabetic control.

As type 1 and type diabetes is a condition where the main problem is elevated blood sugar levels, it seems there is value in being able to measure your blood sugars and discover how it is best kept under control. One good reason to know your sugar level is under control is this: the connection between high blood sugar levels and those diabetic complications!

Research shows neuropathy appears to come about when your blood sugars remain over 140 mg/dl (7.8 mmol/l) for two hours or more… this is when you are at the pre-diabetic stage. Actually many type 2 diabetics at the time of diagnosis have detectable neuropathy… this is due to the fact most diabetics have had elevated blood sugars for ten years prior to diagnosis. The blood glucose reading to confirm a diagnosis of type 2 diabetes is 200 mg/dl (11.1 mmol/l).

What is your self monitored blood sugar target?

Many diabetics have the following target but check with your health care practitioner and discuss the best levels for you. Sometimes targets change as you mature or complications develop.

• fasting BSL or pre-meal… between 90 and 130 mg/dl (5 and 7.2 mmol/l)
• one or two hours following your meal… less than 180 mg/dl (10 mmol/l)
• before going to bed… between 110 and 150 mg/dl (6.1 and 8.3 mmol/l)

Self monitoring gives you the ability to make choices about the foods you eat, and which physical exercise you should participate in to help lower your blood sugar levels. Always write your results in a logbook along with details of what you were doing at the time, for example swimming, hiking or drinking alcohol at a party.

Study findings indicate that once-weekly
exenatide is a good option for add-on therapy in patients with Type
2 diabetes for whom hypoglycemia, weight loss, and convenience are
concerns, say researchers.

The results of two randomized trials - DURATION-2 and DURATION-3
- showed that a long-acting formulation of exenatide given once
weekly produced greater reductions in glycated hemoglobin (HbA1c)
than sitagliptin, pioglitazone, and insulin glargine in patients
with inadequate glycemic control, alongside greater weight loss and
fewer hypoglycemic events.

The findings of both trials were presented this week at the
American Diabetes Association 2010 Scientific Sessions held in
Orlando, Florida, and simultaneously published in separate papers
by The Lancet.

DURATION-2 was set up to compare the efficacy and tolerability
of injected exenatide 2 mg/week (n=160), oral sitagliptin 100
mg/day (n=166), and oral pioglitazone 45 mg/day (n=165) as add-on
therapies to metformin 1480-1583 mg/day over 26 weeks. To minimize
bias patients receiving oral treatments also received a weekly
injected placebo, while those receiving injected exenatide also
received a daily oral placebo.

Lead investigator Richard Bergenstal (International Diabetes
Center, Minneapolis, Minnesota, USA) presented the results at the
ADA meeting. He reported that reductions in HbA1c at study
completion were significantly greater in the exenatide once-weekly
group, at a mean of 1.5%, compared with reductions of 0.9% and 1.2%
in the sitagliptin and piogliazone groups, respectively. This
translated to treatment differences of -0.6% and -0.3% between
exenatide and sitagliptin and exenatide and pioglitazone,
respectively.

Significantly more patients on exenatide therapy achieved a
target HbA1c of less than 7% by the end of the study than did those
taking sitagliptin or pioglitazone, at 59% versus 31% and 44%,
respectively.

Average weight loss with exenatide (2.3 kg) was significantly
greater than that with sitagliptin and piogliazone by 1.5 kg and
5.1 kg, respectively.

Notably, exenatide therapy significantly reduced systolic blood
pressure by 3.5 mmHg from baseline. A smaller, nonsignificant
reduction of 1.5 mmHg was observed for pioglitazone and there was
no reduction with sitagliptin.

Bergenstal said that “some, but not all” of the blood pressure
reduction observed is likely to be due to the beneficial effects of
weight loss.

Regarding adverse events, nausea and diarrhea were the most
common in exenatide- and sitagliptin-treated patients, at 24% and
10% versus 18% and 10%, respectively. For pioglitazone, upper
respiratory tract infection and peripheral edema were the most
common and occurred in a respective 10% and 8% of participants.

In DURATION-3, Michaela Diamant (VU University Medical Centre,
Amsterdam, The Netherlands) and colleagues compared the efficacy of
treatment with once-weekly exenatide injection (n=228) with that of
daily injections of insulin glargine (n=220) titrated to glucose
targets in individuals with Type 2 diabetes who had poor glycemic
control despite being treated with glucose-lowering medication for
3 months or more.

At 26 weeks, the researchers found that HbA1c was reduced to a
greater extent in the exenatide- than the insulin glargine-treated
patients, by 1.5% versus 1.3%. Weight loss was also significantly
better in the exenatide group than the insulin glargine group, with
a between group difference of 4 kg.

In contrast, fasting serum glucose was reduced to a greater
extent in the insulin glargine than the exenatide group, by 2.8
versus 2.1 mmol/l.

Significantly more patients had discontinued exenatide than
insulin glargine treatment by the end of the study period, at 5%
and 1%, respectively. This difference could mostly be explained by
a small number of patients who discontinued treatment due to an
injection site reaction in the exenatide group (n=4; 2%).

Diamant and team recognize the importance of collecting
longer-term data and say that a planned extension to DURATION-3 of
up to 2.5 years is currently in progress.

“We found that exenatide produced a superior reduction in HbA1c
compared with insulin glargine,” said Diamant. “However, the
clinical relevance must be discussed and if we consider not only
glycemic control in our patients but also body weight gain and
incidence of hypoglycemia then this therapy is a good one to
consider.”

Writing in a related Comment article in The Lancet, Anoop
Misra (Fortis Hospital, New Delhi, India) and Shashank Joshi
(Bhatia Hospital, Mumbai, India) agreed with this conclusion. But
they also noted that the some important “unknowns” remain about
treatment with long-acting exenatide.

These include that “the long-term effects of sustained use of a
glucagon-like peptide-1 receptor agonist on pancreatic beta cells
in human beings are not known,” while “renal dysfunction, recently
observed during exenatide therapy, needs continuing
pharmacovigilance.”

MedWire (www.medwire-news.md) is an independent clinical news
service provided by Current Medicine Group, a trading division of
Springer Healthcare Limited. © Springer Healthcare Ltd;
2010

Journal

Add-on treatment with liraglutide improves glycemic control without causing major hypoglycemia or weight gain, a trial in patients with Type 2 diabetes has found.

The study suggests that liraglutide, a new once-daily human analogue of glucagon-like peptide-1 (GLP-1), may be a useful new treatment in patients who are suboptimally controlled on sulfonylurea monotherapy.

Liraglutide mimics the glucoregulatory actions of endogenous GLP-1 by targeting the incretin system, and has been shown to bring about sustained improvements in glycemic control, beta-cell function, and weight, with a low risk for hypoglycemia.

The present study evaluated the safety and efficacy of liraglutide in 264 Japanese patients with a mean body mass index of 24.9 kg/m² and mean glycated hemoglobin (HbA1c) level of 8.4%. They were randomly assigned to take liraglutide 0.6 mg/day, liraglutide 0.9 mg/day, or placebo, each added to sulfonylurea monotherapy, for 24 weeks.

At the end of the study period, HbA1c had fallen by 1.56%, 1.46%, and 0.40% in the liraglutide 0.9 mg/day, 0.6 mg/day, and placebo groups, respectively. The differences between active treatment and placebo were statistically significant.

Furthermore, a significantly greater proportion of patients in the liraglutide treatment groups had achieved target HbA1c levels of less than 7.0% (46.5% with lower-dose and 71.3% with higher-dose liraglutide versus 14.8% with placebo).

Liraglutide treatment was also associated with significant reductions in fasting plasma glucose and postprandial plasma glucose.

Finally, overall safety was comparable among the three groups. There were no major hypoglycemic episodes in any group and body weight was unchanged in both liraglutide groups, whereas mean weight fell by 1.12 kg in the placebo group.

Writing in the journal Diabetes, Obesity, and Metabolism, Kohei Kaku (Kawasaki Medical School, Okayama, Japan) and fellow investigators say that liraglutide provides “superior glycemic control” compared with placebo, offering sustained and significant reductions in HbA1c in a dose-dependent manner.

They conclude: “In Japanese subjects with Type 2 diabetes, once-daily liraglutide administered at 0.9 mg/day is both effective and well-tolerated in combination with sulfonylurea agents, demonstrating significantly greater glycemic control than sulfonylurea monotherapy, without causing adverse weight gain or loss.”

A 28-week follow-up study of the study participants is ongoing and will provide long-term safety and efficacy data.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

Free abstract

A 5-year study shows no evidence of increased risk for development or progression of diabetic retinopathy with insulin glargine compared with neutral protamine Hagedorn (NPH) insulin, report researchers in the journal Diabetologia.

In an open-label study to confirm the retinal safety profile of insulin glargine, Julio Rosenstock (Dallas Diabetes and Endocrine Center at Medical City, Dallas, Texas, USA) and colleagues randomly assigned 1017 patients with Type 2 diabetes to receive twice-daily NPH insulin or once-daily basal insulin glargine for 5 years.

Patients had no or non-proliferative retinopathy and were treated with oral antidiabetes agents, insulin, or both for at least 1 year prior to screening.

In both groups, insulin doses were titrated over the first 3 years of the study to achieve target fasting plasma glucose (FPG) levels of less than or equal to 6.7 mmol/l. This target was reduced to less than or equal to 5.5 mmol/l for the last 2 years of the study.

The study used 7-field fundus photography and the Early Treatment Diabetic Retinopathy Study (ETDRS) scale to evaluate retinopathy progression. The primary outcome was the percentage of patients with three or more step progression from baseline on the ETDRS scale.

The mean basal insulin dose at endpoint was lower for insulin glargine than for NPH insulin, at 62 IU compared with 72 IU, respectively.

Diabetic retinopathy at baseline was more prevalent in the insulin glargine than the NPH group (15.6% vs 12.1%) and baseline ETDRS score was greater (3.06 vs 2.85). Despite this, three or more step progression of retinopathy was no more frequent in the insulin-glargine than NPH-insulin group (14.2% vs 15.7%).

Other measures of retinopathy, including the development of proliferative diabetic retinopathy and progression to clinically significant macular edema, occurred to a similar degree in each treatment group.

The study also provides important information on the long-term safety of insulin glargine compared with NPH insulin, with no unexpected adverse events emerging during the 5-year study. NPH insulin was associated with a higher incidence of severe hypoglycemia compared with insulin glargine.

Although not a primary endpoint of the trial, a slightly lower glycated hemoglobin (HbA1c) level was seen with NPH insulin (7.6% vs 7.8%) at the end of the study.

The authors suggest that as control of FPG was similar between the two groups, the lower HbA1c in the NPH group was probably due to lower glucose levels during the day related to the higher insulin doses with the twice-daily NPH regimen.

“These results demonstrate that treatment of Type 2 diabetes mellitus with insulin glargine over 5 years was not associated with an increase in progression of diabetic retinopathy, compared with NPH insulin treatment,” conclude the authors.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a pa