Taking the amylin analog pramlintide before meals is as effective as taking a rapid-acting insulin analog for glycemic control in individuals with Type 2 diabetes who are already using basal insulin and oral anti-hyperglycemic medications, say clinicians.

“Adding basal insulin therapy to oral agents improves glycemic control for many patients with Type 2 diabetes, but up to 50% of patients continue to have HbA1C values of over 7% and generally have post-prandial hyperglycemia,” explain Matthew Riddle (Oregon Health and Science University, Portland, USA) and co-workers.

“The usual next step in treatment is addition of insulin injections at meal times,” the authors add, “but this approach increases risks of weight gain and post-prandial hypoglycemia.”

It is thought that this post-prandial hypoglycemia is at least partly due to deficiency in amylin ??” a hormone that slows gastric emptying, increases glucagon secretion and increases satiety.

To test this theory, Riddle and team randomly assigned 113 individuals with Type 2 diabetes to treatment with pramlintide or a rapid-acting insulin analog for 24 weeks. The primary endpoint of the study was an HbA1c level of 7% or lower without weight gain or severe hypoglycemia.

Among the 98 patients who completed the study, the primary study endpoint was significantly more likely to be reached in those given pramlintide than in those given a rapid-acting insulin analog, at a success rate of 30% versus 11%.

Both drugs led to similar reductions in fasting plasma glucose levels, but pramlintide was not associated with any weight gain, whereas those given the insulin analog gained an average of 4.7 kg. Patient reports of mild-to-moderate hypoglycemia were also less common with pramlintide, but nausea was significantly more common with the amylin analog (21%) than the insulin analog (0%).

“Overall, these findings support the role of mealtime pramlintide as a potential alternative to rapid-acting insulin analogs for patients using basal insulin treatment with or without oral antidiabetics who are not achieving glycemic goals,” say the researchers.

Writing in the journal Diabetes Care, they add that “longer-term studies to evaluate cardiovascular and microvascular outcomes of controlling after-meal hyperglycemia without weight gain and hypoglycemia would be helpful to inform clinical treatment decisions for patients with Type 2 diabetes.”

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

Diabetes is a dangerous disease when it is left undiagnosed and untreated. For such an easy disease to detect and to screen for, it is amazing the number of people whose diabetes goes undetected and so untreated.

First of all, there are two different types of diabetes that affect many things concerning treatment. Type 1 diabetes involves failure of the pancreas to produce insulin. Insulin is an important hormone that allows the body to convert sugars and starches into energy for the cells. Without it, the sugars stay in the blood stream and accomplish nothing. Type 2 diabetes, on the other hand, is much more common than Type 1 diabetes. It is the type of diabetes in which a person’s pancreas cannot produce enough insulin to keep up with demand or the body is no longer able to use the insulin produced by the body. Type 1 patients are much less common (roughly 10% of all cases) but are completely insulin injection dependent. Type 2 patients can generally control the disease through diet and lifestyle changes.

Diabetes is a very serious health condition. It is such a serious condition that the life expectancy of diabetics is approximately 10 years less than that of non-diabetics. This is because of the numerous complications that go hand in hand with diabetes. Coronary artery disease, peripheral vascular disease, blindness or vision loss, kidney problems, circulation issues, and loss of circulation in both the hands and feet are all common side effects of diabetes that has not been treated or managed properly.

Considering the dangers of not controlling diabetes, it is scary how many have diabetes undiagnosed. An individual with undiagnosed diabetes is an individual who has not been diagnosed by a doctor or physician but whose plasma glucose levels are well within the accepted criteria for diabetes. The United States is estimated to have an undiagnosed diabetes population of 2.7% of the entire adult population over the age of 20.

This percentage means that nearly 3% of the adult population are putting their bodies at risk by not having control of their diabetes because they have not had it diagnosed. A simple blood test is really all that is needed to determine if a person is diabetic or not. This is generally part of any general physical conducted on an adult, since blood tests can tell so much about a person’s overall health. The level of undiagnosed diabetics suggests that at least some blood tests are not being interpreted appropriately.

Progressive loss of beta cell function is the main determinant of progression from normal glucose tolerance (NGT) to impaired glucose tolerance (IGT), a US study has found.

Glucose intolerance is a continuum and declines progressively throughout the entire range of NGT and IGT, say R DeFronzo, from the University of Texas Health Science Center in San Antonio, USA.

They note that there has been a lack of large studies characterizing the pathophysiological disturbances responsible for IGT and employing sophisticated measures of beta cell function and insulin sensitivity.

For their study, the researchers examined the determinants of oral glucose tolerance in 602 people with IGT who participated in the Actos Now for Prevention of Diabetes (ACT NOW) study, along with 115 people with NGT and 50 with impaired fasting glucose (IFG) who were identified during screening. Insulin secretion and insulin sensitivity indices were derived from plasma glucose and insulin during an oral glucose tolerance test (OGTT).

At baseline, fasting plasma glucose, 2-hour postprandial glucose (OGTT) and hemoglobin A_1c were, on average, 5.8 mmol/l, 10.5 mmol/l and 5.5%, respectively, in participants with IGT.

IGT was associated with defects in early and total insulin secretion and in insulin sensitivity. IGT patients who had a 2-hour plasma glucose level of 7.8 “8.3 mmol/l, had a 63% decrease in scores on the insulin sensitivity/insulin resistance index compared with NGT participants. Moreover, this defect worsened progressively as 2-hour plasma glucose levels rose, with a 73% decrease in those with levels of 8.9 “9.94 mmol/l and an 80% decrease in those with levels of 10.0 “11.05 mmol/l.

The Matsuda insulin sensitivity index was significantly reduced by 40% in IGT compared with NGT participants. In multivariate analysis, beta cell function was the primary determinant of glucose area under the curve during OGTT, explaining 62% of the variance.

Writing in the journal Diabetologia, the researchers conclude: “The two major pathophysiological disturbances ” insulin resistance and beta cell dysfunction ” declined progressively over the range of NGT and IGT. Participants in the upper tertile of IGT lost approximately 80% of their beta cell function compared with participants with NGT.”

They comment: “The establishment of defined glucose cut-off points for the diagnosis of IGT and Type 2 diabetes is somewhat arbitrary and needs to be re-evaluated.”

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; 2009

Free abstract

A novel fixed-dose combination tablet of repaglinide plus metformin provides comparable glycemic control to a rosiglitazone plus metformin tablet, show results from a phase III study.

Combining oral agents into fixed-dose combination tablets offers potential increased convenience for patients and increased compliance with therapy.

Philip Raskin (University of Texas Southwestern Medical Center, Dallas, Texas, USA) and colleagues compared the efficacy and safety of the recently-approved repaglinide/metformin fixed-dose combination tablet with an existing rosiglitazone/metformin formulation.

In the 26-week study, 561 individuals with Type 2 diabetes not adequately controlled with mono- or dual oral antidiabetes medication were randomized in a 1:1:1 fashion to a repaglinide/metformin fixed-dose combination tablet either twice, or three times daily, or a rosiglitazone/metformin fixed-dose combination tablet twice daily.

The study was designed to test primarily whether treatment with the repaglinide/metformin single-tablet combination is noninferior to treatment with a rosiglitazone/metformin tablet as measured by changes in glycated hemoglobin (HbA1c), and secondly that treatment with repaglinide/metformin twice daily is noninferior to three times daily treatment.

“The repaglinide/metformin fixed-dose combination was shown here to be noninferior to rosiglitazone/metformin,” report the authors in the journal Diabetes, Obesity and Metabolism.

Final changes in HbA1c were not significantly different between the repaglinide/metformin and the rosiglitazone/metformin treatment arms, although reductions were observed earlier with repaglinide/metformin.

In contrast, rosiglitazone/metformin showed significantly greater reductions in fasting plasma glucose at weeks 18 and 26 than repaglinide/metformin.

The authors attribute this observation to the mechanisms of action of the two compounds. An insulin sensitizer such as rosiglitazone is more likely to improve fasting plasma glucose levels, whereas an insulin secretagogue such as repaglinide taken at mealtime is more likely to improve postprandial glucose excursions.

Rosiglitazone/metformin had a mostly adverse effect on lipid profiles. Triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol all increased in this group, while the same parameters all decreased or were essentially unchanged during treatment with repaglinide/metformin.

As expected, hypoglycemic episodes were more frequent with repaglinide/metformin than rosiglitazone/metformin (38.8% vs 10.2%, respectively), although there were no episodes of severe hypoglycemia.

In the rosiglitazone/metformin group, peripheral edema was reported in 6.5% of individuals, but in only 2.1% of individuals in the repaglinide/metformin group. Overall adverse event profiles were comparable between treatment groups.

“This new repaglinide/metformin fixed-dose combination twice daily had efficacy comparable to that of the rosiglitazone/metformin fixed-dose combination twice daily currently in clinical use,” conclude the authors.

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